Real-world walking cadence in people with COPD.

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence. Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries. Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day-1. Mean walking cadence was 88±9 steps·min-1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1, 6-min walk distance, physical activity (steps·day-1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min-1, 95% CI 0.91-0.99, p=0.009). Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.

Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2.

INTRODUCTION: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. METHODS: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. RESULTS: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82-36.32], p = 0.006). CONCLUSION: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

Short-term effects of air pollution and weather on physical activity in patients with chronic obstructive pulmonary disease (COPD).

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) accumulate low levels of physical activity. How environmental factors affect their physical activity in the short-term is uncertain. AIM: to assess the short-term effects of air pollution and weather on physical activity levels in COPD patients. METHODS: This multi-center panel study assessed 408 COPD patients from Catalonia (Spain). Daily physical activity (i.e., steps, time in moderate-to-vigorous physical activity (MVPA), locomotion intensity, and sedentary time) was recorded in two 7-day periods, one year apart, using the Dynaport MoveMonitor. Air pollution (nitrogen dioxide (NO2), particulate matter below 10 µm (PM10) and a marker of black carbon (absorbance of PM2.5: PM2.5ABS), and weather (average and maximum temperature, and rainfall) were estimated the same day (lag zero) and up to 5 days prior to each assessment (lags 1-5). Mixed-effect distributed lag linear regression models were adjusted for age, sex, weekday, public holidays, greenness, season, and social class, with patient and city as random effects. RESULTS: Patients (85% male) were on average (mean ± SD) 68 ± 9 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 ± 18% predicted. Higher NO2, PM10 and PM2.5ABS levels at lag four were associated with fewer steps, less time in MVPA, reduced locomotion intensity, and longer sedentary time (e.g., coefficient (95% CI) of -60 (-105, -15) steps per 10 µg/m3 increase in NO2). Higher average and maximum temperatures at lag zero were related to more steps and time in MVPA, and less sedentary time (e.g., +85 (15, 154) steps per degree Celsius). Higher rainfall at lag zero was related to fewer steps and more sedentary time. CONCLUSION: Air pollution affects the amount and intensity of physical activity performed on the following days in COPD patients, whereas weather affects the amount of physical activity performed on the same day.

Pulmonary hypertension in interstitial lung disease and in chronic obstructive pulmonary disease: different entities?

PURPOSE OF REVIEW: Pulmonary hypertension (PH) is a common complication of both chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), classified as Group 3 PH. To which extent PH presents and behaves similarly in COPD and ILD is unclear. This review examines the similarities and differences in pathogenesis, clinical presentation, natural history and treatment response of PH in COPD and ILD. RECENT FINDINGS: The latest studies on PH in chronic lung disease have re-evaluated the role of traditionally held etiopathogenetic factors such as tobacco exposure and hypoxia, although new ones such as airborne pollutant and genetic mutations are increasingly recognized. We examine common and diverging factors involved in PH development in COPD and ILD, as well as common and diverging clinical features of presentation, natural history and response to treatment and highlight areas for future research. SUMMARY: The development of PH in lung disease significantly worsens the morbidity and mortality of patients with COPD and ILD. However, recent findings show importance of recognizing distinct patterns and behaviors of pulmonary vascular disease, taking into account the specific underlying lung disease and severity of the hemodynamic involvement. Further studies are needed to build evidence on these aspects, especially in early disease.

Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension.

INTRODUCTION: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence. METHODS: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity. RESULTS: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased (p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training (p < 0.05). CONCLUSION: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response.

Nitrosative and Oxidative Stress, Reduced Antioxidant Capacity, and Fiber Type Switch in Iron-Deficient COPD Patients: Analysis of Muscle and Systemic Compartments.

We hypothesized that a rise in the levels of oxidative/nitrosative stress markers and a decline in antioxidants might take place in systemic and muscle compartments of chronic obstructive pulmonary disease (COPD) patients with non-anemic iron deficiency. In COPD patients with/without iron depletion (n = 20/group), markers of oxidative/nitrosative stress and antioxidants were determined in blood and vastus lateralis (biopsies, muscle fiber phenotype). Iron metabolism, exercise, and limb muscle strength were assessed in all patients. In iron-deficient COPD compared to non-iron deficient patients, oxidative (lipofuscin) and nitrosative stress levels were greater in muscle and blood compartments and proportions of fast-twitch fibers, whereas levels of mitochondrial superoxide dismutase (SOD) and Trolox equivalent antioxidant capacity (TEAC) decreased. In severe COPD, nitrosative stress and reduced antioxidant capacity were demonstrated in vastus lateralis and systemic compartments of iron-deficient patients. The slow- to fast-twitch muscle fiber switch towards a less resistant phenotype was significantly more prominent in muscles of these patients. Iron deficiency is associated with a specific pattern of nitrosative and oxidative stress and reduced antioxidant capacity in severe COPD irrespective of quadriceps muscle function. In clinical settings, parameters of iron metabolism and content should be routinely quantify given its implications in redox balance and exercise tolerance.

Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance.

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. In the vastus lateralis and blood of severe COPD patients with/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance.

Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial

Introduction: Iron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level<100ng/mL or a ferritin level between 100 and 299ng/mL with a transferrin saturation<20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry. Results: We included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p=0.009; relative risk 3.12, (95% CI, 1.19–8.12)]. CAT score decreased −3 (−6.0–1.3) points from baseline in the intervention group (p=0.007), in contrast to placebo group [−1 (−4.0–2.3) points, p=0.236] with no differences in DPA and adverse events in both groups. Conclusions: Iron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated. (AU)

Respuesta a «Ausencia de efectos clínicos destacables del SARS-CoV-2 sobre la afinidad de la hemoglobina por el O2 en pacientes con COVID-19» / Reply to «Absence of Relevant Clinical Effects of SARS-CoV-2 on the Affinity of Hemoglobin for O2 in Patients with COVID-19»

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[Translated article] Reply to “Absence of Relevant Clinical Effects of SARS-CoV-2 on the Affinity of Hemoglobin for O2 in Patients With COVID-19” / Respuesta a «Ausencia de efectos clínicos destacables del SARS-CoV-2 sobre la afinidad de la hemoglobina por el O2 en pacientes con COVID-19»

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Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial.

INTRODUCTION: Iron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level<100ng/mL or a ferritin level between 100 and 299ng/mL with a transferrin saturation<20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry. RESULTS: We included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p=0.009; relative risk 3.12, (95% CI, 1.19-8.12)]. CAT score decreased -3 (-6.0-1.3) points from baseline in the intervention group (p=0.007), in contrast to placebo group [-1 (-4.0-2.3) points, p=0.236] with no differences in DPA and adverse events in both groups. CONCLUSIONS: Iron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated. CLINICAL TRIAL REGISTRATION: EudraCT 2016-001238-89.

Roles of the physical environment in health-related quality of life in patients with chronic obstructive pulmonary disease.

RATIONALE: Many clinical and psychological factors are known to influence the health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). However, research on whether environmental factors, such as air pollution, noise, temperature, and blue/green spaces also influence HRQL in COPD has not been systematically investigated. OBJECTIVE: To assess the relationship between air pollution, road traffic noise, temperature, and distance to blue/green spaces and respiratory-specific HRQL in COPD. METHODS: We used cross-sectional data from a multicenter study in 407 stable mild-to-very severe COPD patients from Barcelona (Catalonia). Patients answered the COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). Individual residential exposure to air pollutants (nitrogen dioxide [NO2] and particulate matters of varying aerodynamic diameters [PM2.5, PM10, and PM2.5absorbance]), road traffic noise (Lden), and land surface temperature were estimated using long-term averages from land-use regression models, 24-h noise maps, and land surface temperature maps, respectively. We measured residential distances to blue/green spaces from the Urban Atlas. We used mixed-effect negative binomial (for CAT) and linear (for CCQ) regression models, adjusted for potential confounders, with a random effect by center. RESULTS: Of those patients, 85 % were male and had a mean (SD) age of 69 (9) years, CAT score of 12 (7), CCQ-total score of 1.4 (1.0), and post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 (18) %predicted. We found that NO2 and PM2.5absorbance were associated with worsened CAT and CCQ-mental scores, e.g., 0.15-unit change in CAT score [regression coefficient (ß) = 0.15; 95 % confidence interval (CI) = 0.03, 0.26] per interquartile range in NO2 [13.7 µg/m3]. Greater distances to blue/green spaces were associated with worsened CCQ-mental scores [0.08; 0.002, 0.15]. CONCLUSIONS: Our study showed that increased air pollution, particularly NO2 and PM2.5absorbance and greater distances to blue/green spaces negatively influence HRQL in COPD patients. These findings have important implications for the WHO promotion to develop healthy cities for our future.

Physical activity and cardiac autonomic dysfunction in patients with chronic obstructive pulmonary disease: A cross-sectional analysis.

BACKGROUND: The cardiac autonomic function in patients with chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVES: We aimed to 1) describe the cardiac autonomic function assessed by heart rate recovery (HRR) and chronotropic response (CR) during a 6-min walk test (6MWT) and afterward and 2) estimate the association of physical activity with HRR and CR in COPD patients. METHODS: This cross-sectional analysis included 320 patients with mild to very severe COPD. Physical activity (steps, time in any/moderate-to-vigorous/vigorous physical activity, intensity and sedentary time) was measured during 1 week by accelerometer. CR and HRR were measured during a 6MWT and 5min after, respectively, and their association with physical activity parameters was estimated by multivariable linear regression models. RESULTS: Patients were 82% male and had a mean (SD) age 68 (8) years, post-bronchodilator FEV1 57 (18) % predicted, and walked a mean of 7716 (4139) steps/day. HRR was slow until 5min after the 6MWT; the mean (SD) HRR was 15 (10), 22 (11), 25 (12), 25 (12) and 27 (12) bpm after 1, 2, 3, 4 and 5min, respectively. The mean (SD) CR was 35% (16). After adjusting for relevant confounders, time in vigorous physical activity was significantly associated with a fast decrease in HRR (p=0.044) and an increase in CR (p=0.021). We found no independent association for other physical activity parameters. CONCLUSION: A cardiac autonomic dysfunction is present in patients with mild to very severe COPD and is inversely related to the practice of vigorous physical activity. Trial registration ClinicalTrials.gov NCT01897298.

Absence of relevant clinical effects of SARS-COV-2 on the affinity of hemoglobin for O2 in patients with COVID-19 / Ausencia de efectos clínicos destacables del SARS-CoV-2 sobre la afinidad de la hemoglobina por el O2 en pacientes con COVID-19

Pulmonary involvement in COVID-19 is frequently associated with alterations in oxygenation. The arterial partial pressure of oxygen (PaO2) is the most clinically used variable to assess such oxygenation, since it decisively influences the oxygen transported by hemoglobin (expressed by its percentage of saturation, SaO2). However, two recent studies conducted respectively in silico and using omic techniques in red blood cells of COVID-19 patients have suggested that SARS-CoV-2 could decrease the affinity of oxygen for the hemoglobin (which would imply that PaO2 would overestimate SaO2), and also reduce the amount of this carrier molecule.Objective: To evaluate this hypothesis in blood samples from COVID-19 patients. Methods: Blood gases of all COVID-19 patients performed in our laboratory in two months were included, as well as those from two control groups: synchronous patients with negative PCR for SARS-CoV-2 (SCG) and a historical group (HCG). Both SaO2 and venous saturations (SvO2) measured by cooximetry (COX) were compared separately with those calculated using the Kelman (K), Severinghaus (SV) and Siggaard-Andersen (SA) equations in each group. Results: Measured and calculated SaO2 and SvO2 were practically equivalent in all groups. Intraclass correlation coefficients (ICC) for SaO2 in COVID-19 were 0.993 for COX-K and 0.992 for both COX-SV and COX-SA; being 0.995 for SvO2 for either COX-K, COX-SV or COX-SA. Hemoglobin and ferritin were slightly higher in COVID-19 compared to SCG and HCG (hemoglobin, p < 0.001 for both; ferritin, p < 0.05 for SCG and p < 0.001 for HCG). Conclusion: Under clinical conditions SARS-CoV-2 does not have an appreciable influence on the affinity of oxygen for the hemoglobin, nor on the levels of this carrier molecule. Therefore, PaO2 is a good marker of blood oxygenation also in COVID-19. (AU)

La afectación pulmonar por COVID-19 se asocia frecuentemente con alteraciones en la oxigenación. La presión parcial arterial de oxígeno (PaO2) es la variable más utilizada clínicamente para valorar dicha oxigenación, ya que influye decisivamente en el oxígeno transportado por la hemoglobina (expresado por porcentaje de saturación, SaO2). Sin embargo, dos estudios recientes realizados respectivamente in silico y mediante técnicas ómicas en hematíes de pacientes han sugerido que SARS-CoV-2 podría disminuir la afinidad del oxígeno por la hemoglobina (lo que implicaría que la PaO2 sobrevaloraría la SaO2 real), e incluso reduciría la cantidad de esta molécula transportadora.Objetivo: Evaluar dicha hipótesis en muestras gasométricas de pacientes con COVID-19. Métodos: Se incluyeron las gasometrías de todos los pacientes con COVID-19 realizadas en nuestro laboratorio, así como las de dos grupos control: pacientes sincrónicos con PCR negativa (GCS) y grupo histórico (GCH). Se compararon por separado las SaO2 y saturaciones venosas (SvO2), medidas por cooximetría (COX) con las calculadas mediante las ecuaciones de Kelman (K), Severinghaus (SV) y Siggaard-Andersen (SA) en cada grupo. Resultados: Las cifras de SaO2 y SvO2 medidas y calculadas fueron prácticamente superponibles en todos los grupos. Así, los coeficientes de correlación intraclase (CCI) en COVID-19 para SaO2 fueron 0,993 en COX-K y 0,992 en COX-SV y COX-SA; siendo 0,995 para SvO2 tanto en COX-K como en COX-SV y COX-SA. La hemoglobina y la ferritina resultaron algo superiores en el grupo COVID-19 respecto de GCS y GCH (hemoglobina, p < 0,001 en ambos; ferritina, p < 0,05 para GCS y p < 0,001 para GCH). Conclusiones: En condiciones clínicas, el SARS-CoV-2 no influye de forma apreciable en la afinidad del oxígeno por la hemoglobina, ni tampoco en los niveles de esta última. Por tanto, la PaO2 es un buen marcador de oxigenación sanguínea también en COVID-19. (AU)

Absence of relevant clinical effects of SARS-COV-2 on the affinity of hemoglobin for O2 in patients with COVID-19.

Pulmonary involvement in COVID-19 is frequently associated with alterations in oxygenation. The arterial partial pressure of oxygen (PaO2) is the most clinically used variable to assess such oxygenation, since it decisively influences the oxygen transported by hemoglobin (expressed by its percentage of saturation, SaO2). However, two recent studies conducted respectively in silico and using omic techniques in red blood cells of COVID-19 patients have suggested that SARS-CoV-2 could decrease the affinity of oxygen for the hemoglobin (which would imply that PaO2 would overestimate SaO2), and also reduce the amount of this carrier molecule. OBJECTIVE: To evaluate this hypothesis in blood samples from COVID-19 patients. METHODS: Blood gases of all COVID-19 patients performed in our laboratory in two months were included, as well as those from two control groups: synchronous patients with negative PCR for SARS-CoV-2 (SCG) and a historical group (HCG). Both SaO2 and venous saturations (SvO2) measured by cooximetry (COX) were compared separately with those calculated using the Kelman (K), Severinghaus (SV) and Siggaard-Andersen (SA) equations in each group. RESULTS: Measured and calculated SaO2 and SvO2 were practically equivalent in all groups. Intraclass correlation coefficients (ICC) for SaO2 in COVID-19 were 0.993 for COX-K and 0.992 for both COX-SV and COX-SA; being 0.995 for SvO2 for either COX-K, COX-SV or COX-SA. Hemoglobin and ferritin were slightly higher in COVID-19 compared to SCG and HCG (hemoglobin, p < 0.001 for both; ferritin, p < 0.05 for SCG and p < 0.001 for HCG). CONCLUSION: Under clinical conditions SARS-CoV-2 does not have an appreciable influence on the affinity of oxygen for the hemoglobin, nor on the levels of this carrier molecule. Therefore, PaO2 is a good marker of blood oxygenation also in COVID-19.

La afectación pulmonar por COVID-19 se asocia frecuentemente con alteraciones en la oxigenación. La presión parcial arterial de oxígeno (PaO2) es la variable más utilizada clínicamente para valorar dicha oxigenación, ya que influye decisivamente en el oxígeno transportado por la hemoglobina (expresado por porcentaje de saturación, SaO2). Sin embargo, dos estudios recientes realizados respectivamente in silico y mediante técnicas ómicas en hematíes de pacientes han sugerido que SARS-CoV-2 podría disminuir la afinidad del oxígeno por la hemoglobina (lo que implicaría que la PaO2 sobrevaloraría la SaO2 real), e incluso reduciría la cantidad de esta molécula transportadora. OBJETIVO: Evaluar dicha hipótesis en muestras gasométricas de pacientes con COVID-19. MÉTODOS: Se incluyeron las gasometrías de todos los pacientes con COVID-19 realizadas en nuestro laboratorio, así como las de dos grupos control: pacientes sincrónicos con PCR negativa (GCS) y grupo histórico (GCH). Se compararon por separado las SaO2 y saturaciones venosas (SvO2), medidas por cooximetría (COX) con las calculadas mediante las ecuaciones de Kelman (K), Severinghaus (SV) y Siggaard-Andersen (SA) en cada grupo. RESULTADOS: Las cifras de SaO2 y SvO2 medidas y calculadas fueron prácticamente superponibles en todos los grupos. Así, los coeficientes de correlación intraclase (CCI) en COVID-19 para SaO2 fueron 0,993 en COX-K y 0,992 en COX-SV y COX-SA; siendo 0,995 para SvO2 tanto en COX-K como en COX-SV y COX-SA. La hemoglobina y la ferritina resultaron algo superiores en el grupo COVID-19 respecto de GCS y GCH (hemoglobina, p < 0,001 en ambos; ferritina, p < 0,05 para GCS y p < 0,001 para GCH). CONCLUSIONES: En condiciones clínicas, el SARS-CoV-2 no influye de forma apreciable en la afinidad del oxígeno por la hemoglobina, ni tampoco en los niveles de esta última. Por tanto, la PaO2 es un buen marcador de oxigenación sanguínea también en COVID-19.

Iron Replacement and Redox Balance in Non-Anemic and Mildly Anemic Iron Deficiency COPD Patients: Insights from a Clinical Trial.

In COPD patients, non-anemic iron deficiency (NAID) is a common systemic manifestation. We hypothesized that in COPD patients with NAID, iron therapy may improve systemic oxidative stress. The FACE (Ferinject assessment in patients with COPD and iron deficiency to improve exercise tolerance) study was a single-blind, unicentric, parallel-group, placebo-controlled clinical trial (trial registry: 2016-001238-89). Sixty-six patients were enrolled (randomization 2:1): iron arm, n = 44 and placebo arm, n = 22, with similar clinical characteristics. Serum levels of 3-nitrotyrosine, MDA-protein adducts, and reactive carbonyls, catalase, superoxide dismutase (SOD), glutathione, Trolox equivalent antioxidant capacity (TEAC), and iron metabolism biomarkers were quantified in both groups. In the iron-treated patients compared to placebo, MDA-protein adducts and 3-nitrotyrosine serum levels significantly declined, while those of GSH increased and iron metabolism parameters significantly improved. Hepcidin was associated with iron status parameters. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers along with an improvement in GSH levels in patients with stable severe COPD. Hepcidin may be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases. These findings have potential clinical implications in the management of patients with severe COPD.