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Heteroatom-tagged proteomics allows the absolute quantification of selenoproteins using the heteroatom as a “tag” into a selective and sensitive atomic detector instead of a molecular one. Using this analytical method, about 90% of total selenium in human serum/plasma can be measured as selenoproteins and total selenometabolites and thus, the status of selenium can be determined. Herein, we determined the absolute concentration of selenoproteins in human serum patients with lung cancer (LC) and chronic obstructive pulmonary disease (COPD), a competing cause of morbidity and mortality in smokers as well as an independent risk factor for LC. We conducted an observational study of 154 human serum samples obtained from LC and COPD patients with varying severity of disease, including COPD patients who developed LC during follow-up and healthy controls (HC). Using heteroatom-tagged proteomics, we determined extracellular glutathione peroxidase (eGPx), selenoprotein P (SELENOP), and selenoalbumin (SeAlb). Associations between selenoproteins were also studied as potential biomarkers of disease. The concentration of eGPx was significantly higher in the all-inclusive COPD cohort compared to HC, COPD patients with LC, or those with mild obstructive lung disease, while SELENOP concentration was significantly decreased in LC patients compared to HC and COPD. We found an inverse correlation between SELENOP and SeAlb in HC, but also in LC patients, and especially in patients with COPD and LC. Moreover, we found that eGPx and selenometabolite concentrations were positively associated with LC human serum. Selenoprotein concentrations were altered in COPD and LC when compared to healthy controls suggesting a potential role of the selenoproteome in the diagnosis and/or treatment of these tobacco-related diseases.

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., Depto. de Medicina, Fac. de Medicina, TRUE, pub

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.

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.

Fernando González-Torralba,1 Adolfo Baloira,2 Araceli Abad,3 Antonia Fuster,4 Juan Luis García-Rivero,5 Patricia García-Sidro,6 Eduardo Márquez-Martín,7 Marta Palop,8 Néstor Soler,9 José Luis Velasco10 1Respiratory Department, University Hospital of Aranjuez, Madrid, Spain; 2Respiratory Department, University Hospital of Pontevedra, Pontevedra, Spain; 3Respiratory Department, University Hospital of Getafe, Madrid, Spain; 4Respiratory Department, University Hospital Son Llatzer, Palma de Mallorca, Spain; 5Respiratory Department, University Hospital Marqués de Valdecilla, Santander, Spain; 6Respiratory Department, University Hospital of La Plana, Castellón, Spain; 7Respiratory Department, University Hospital Virgen del Rocío, Sevilla, Spain; 8Respiratory Department, Hospital of Sagunto, Valencia, Spain; 9Respiratory Department, Hospital Clinic, Barcelona, Spain; 10Respiratory Department, University Hospital Virgen de la Victoria, Málaga, SpainCorrespondence: Adolfo Baloira, Email adolfo.baloira.villar@sergas.esPurpose: The pharmacological treatment of chronic obstructive pulmonary disease (COPD) is largely based on inhaled bronchodilators. Inspiratory flow and lung deposition are key parameters to be considered in inhaled therapy; however, the relationship between these two parameters, the patient specificities, and the suitability of the inhaler type for COPD management has not been fully addressed. The present study follows a Delphi Panel methodology to find expert consensus on the role of inspiratory flow and lung deposition as key decision factors in COPD inhaled therapy.Methods: A two-round Delphi Panel, consisting of 38 statements (items) and completed by 57 Spanish pulmonologists, was carried out to measure the experts’ consensus degree with each item.Results: A high degree of consensus was reached on most of the items consulted, among these inspiratory flow or inspiratory capacity should be periodically considered when choosing an inhalation devic

Background 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. Methods 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. Results 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. Conclusions 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

[Background] 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., [Methods] 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., [Results] 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., [Conclusions] 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.

[Background] The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression., [Research Question] What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?, [Study Design and Methods] We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time., [Results] The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039)., [Interpretation] Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function., [Trial Registry] ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov

Adolfo Baloira, 1 Araceli Abad, 2 Antonia Fuster, 3 Juan Luis García Rivero, 4 Patricia García-Sidro, 5 Eduardo Márquez-Martín, 6, 7 Marta Palop, 8 Néstor Soler, 9 JL Velasco, 10 Fernando González-Torralba 11 1Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain; 2Hospital Universitario de Getafe, Madrid, Spain; 3Hospital Unvidersitario Son Llàtzer, Palma de Mallorca, Spain; 4Hospital Comarcal de Laredo, Cantabria, Spain; 5Hospital Universitario de la Plana, Castellón, Spain; 6Hospital Virgen del Rocío, Sevilla, Spain; 7CIBERES, Instituto de Salud Carlos III, Madrid, Spain; 8Hospital de Sagunto, Valencia, Spain; 9Hospital Universitario Clínic, Barcelona, Spain; 10Hospital Universitario Virgen de la Victoria, Málaga, Spain; 11Pulmonology Section, Hospital Universitario del Tajo, Aranjuez, SpainCorrespondence: Fernando González-TorralbaPulmonology Section, Hospital Universitario del Tajo, Av. Amazonas Central, s/n, Aranjuez, 28300, Madrid, SpainTel +0034 918 01 41 00Email docbectorralba@hotmail.comBackground: Our aim was to describe: 1) lung deposition and inspiratory flow rate; 2) main characteristics of inhaler devices in chronic obstructive pulmonary disease (COPD).Methods: A systematic literature review (SLR) was conducted to analyze the features and results of inhaler devices in COPD patients. These devices included pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and a soft mist inhaler (SMI). Inclusion and exclusion criteria were established, as well as search strategies (Medline, Embase, and the Cochrane Library up to April 2019). In vitro and in vivo studies were included. Two reviewers selected articles, collected and analyzed data independently. Narrative searches complemented the SLR. We discussed the results of the reviews in a nominal group meeting and agreed on various general principle

Baloira A, Abad A, Fuster A, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:1021–1033. Page 1026, left column, fourth paragraph, the text “Inhaler devices are many times classified as low- (30 L/min or below), medium– (~30–60 L/min), and high- resistance (>60 L/min) devices” should read “Inhaler devices are many times classified as low- (>60 L/min), medium– (~30–60 L/min), and high-resistance (30L/min or below) devices”. The authors apologize for this error. Read the original article

Bernardino Alcazar-Navarrete,1,2 Antonia Fuster,3 Patricia García Sidro,4 Juan Luis García Rivero,5 Beatriz Abascal-Bolado,6 Abel Pallarés-Sanmartín,7 Eduardo Márquez,2,8 Agustin Valido-Morales,9 Ana Boldova Loscertales,10 Francisco Javier Callejas-Gonzalez,11 Marta Palop,12 Juan Antonio Riesco,2,13 Rafael Golpe,14 Juan Jose Soler-Cataluña,2,15 Marc Miravitlles2,16 1AIG De Medicina. Hospital De Alta Resolución De Loja. Agencia Sanitaria Hospital De Poniente, Loja, Granada, Spain; 2CIBERES. Instituto De Salud Carlos III, Madrid, Spain; 3Servicio De Neumología. Hospital Universitario De Son Llatzer, Palma De Mallorca, Spain; 4Servicio De Neumología. Hospital De La Plana, Castellón, Spain; 5Servicio De Neumología. Hospital De Laredo, Laredo, Spain; 6Servicio De Neumología. Hospital Universitario Marqués De Valdecilla, Santander, Spain; 7Servicio De Neumología. Hospital Universitario Alvaro Cunqueiro, Vigo, Spain; 8Unidad Médico-Quirúrgica De Enfermedades Respiratorias. Hospital Virgen Del Rocío, Sevilla, Spain; 9UGC De Neumología. HU Virgen Macarena, Sevilla, Spain; 10Servicio De Neumología. Hospital Royo Villanova, Zaragoza, Spain; 11Servicio De Neumología. Complejo Hospitalario Universitario De Albacete, Albacete, Spain; 12Servicio De Neumología. Hospital De Sagunto, Sagunto, Spain; 13Servicio De Neumología. Hospital San Pedro De Alcántara, Cáceres, Spain; 14Servicio De Neumología. Hospital Universitario Lucus Augusti, Lugo, Spain; 15Servicio De Neumología. Hospital Arnau De Villanova- Lliria, Valencia, Spain; 16Servicio De Neumología. Hospital Universitari Vall De Hebron/Vall d’Hebron Institut De Recerca, Barcelona, SpainCorrespondence: Bernardino Alcazar-Navarrete

Antonia Fuster, Jaume Sauleda, Ernest Sala, Bernardí Barceló1, Jaume Pons2, Miguel Carrera, Aina Noguera1, Bernat Togores, Alvar GN AgustíServeis de Pneumologia, 1Analisis Clinics, and 2Inmunología, Hospital Universitari Son Dureta, Fundación Caubet-Cimera and CIBER Enfermedades Respiratorias, Mallorca, SpainObjective: Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.Patients and methods: To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV1] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV1 98 ± 5% ref).Results: We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.Conclusions: This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.Keywords: COPD, endurance, exercise, IL-10, respiratory muscles, systemic inflammation