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.

Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19.

BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC) infection have caused a significant impact on our health system, but there is limited evidence of approved drugs focused on its prevention. Our objective was to identify risk factors that can determine the presence of PASC, with special attention to the treatment received in the acute phase, and to describe the profile of persistent symptoms in a multidisciplinary Post-Coronavirus Disease-19 (COVID-19) Unit. METHODS: This one-year prospective observational study included patients following an acute COVID-19 infection, irrespective of whether they required hospital admission. A standardized symptom questionnaire and blood sampling were performed at the first follow-up visit, and demographic and clinical electronic data were collected. We compared subjects with PASC with those who had fully recovered. Multivariate logistic regression was performed to identify factors associated with PASC in hospitalized patients, and Kaplan-Meier curves were used to assess duration of symptoms according to disease severity and treatments received in the acute phase. RESULTS: 1966 patients were evaluated; 1081 had mild disease, 542 moderate and 343 severe; around one third of the subjects had PASC, and were more frequently female, with obesity, asthma, and eosinophilia during acute COVID-19 disease. Patients who received treatment with dexamethasone and remdesivir during the course of the acute illness showed a lower median duration of symptoms, compared with those who received none of these treatments. CONCLUSION: Treatment with dexamethasone and/or remdesivir may be useful to reduce the impact of PASC secondary to SARS-CoV-2 infection. In addition, we identified female gender, obesity, asthma, and disease severity as risk factors for having PASC.

Influence of COPD systemic environment on the myogenic function of muscle precursor cells in vitro.

BACKGROUND: Loss of muscle mass and function are well-recognized systemic manifestations of chronic obstructive pulmonary disease (COPD). Acute exacerbations, in turn, significantly contribute to upgrade these systemic comorbidities. Involvement of myogenic precursors in muscle mass maintenance and recovery is poorly understood. The aim of the present study was to investigate the effects of the vascular systemic environment from stable and exacerbated COPD patients on the myogenic behavior of human muscle precursor cells (MPC) in vitro. METHODS: Serum from healthy controls and from stable and exacerbated COPD patients (before and after Methylprednisolone treatment) was used to stimulate human MPC cultures. Proliferation analysis was assessed through BrdU incorporation assays. MPC differentiation was examined through real-time RT-PCR, western blot and immunofluorescence analysis. RESULTS: Stimulation of MPCs with serum obtained from stable COPD patients did not affect myogenic precursor cell function. The vascular systemic environment during an acute exacerbation exerted a mitotic effect on MPCs without altering myogenic differentiation outcome. After Methylprednisolone treatment of acute exacerbated COPD patients, however, the mitotic effect was further amplified, but it was followed by a deficient differentiation capacity. Moreover, these effects were prevented when cells were co-treated with the glucocorticoid receptor antagonist Mifepristone. CONCLUSION: Our findings suggest that MPC capacity is inherently preserved in COPD patients, but is compromised after systemic administration of MP. This finding strengthens the concept that glucocorticoid treatment over the long term can negatively impact myogenic stem cell fate decisions and interfere with muscle mass recovery.

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)

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.

Profile of Clinical and Analytical Parameters in Bronchiectasis Patients during the COVID-19 Pandemic: A One-Year Follow-Up Pilot Study.

Whether the COVID-19 pandemic may have modified the clinical planning and course in bronchiectasis patients remains to be fully elucidated. We hypothesized that the COVID-19 pandemic may have influenced the management and clinical outcomes of bronchiectasis patients who were followed up for 12 months. In bronchiectasis patients (n = 30, 23 females, 66 years), lung function testing, disease severity [FEV1, age, colonization, radiological extension, dyspnea (FACED), exacerbation (EFACED)] and dyspnea scores, exacerbation numbers and hospitalizations, body composition, sputum microbiology, and blood analytical biomarkers were determined at baseline and after a one-year follow-up. Compared to baseline (n = 27, three patients dropped out), in bronchiectasis patients, a significant increase in FACED and EFACED scores, number of exacerbations, and erythrocyte sedimentation rate (ESR) was observed, while FEV1, ceruloplasmin, IgE, IgG, IgG aspergillus, IgM, and IgA significantly decreased. Patients presenting colonization by Pseudomonas aeruginosa (PA) remained unchanged (27%) during follow-up. In bronchiectasis patients, FEV1 declined only after a one-year follow-up along with increased exacerbation numbers and disease severity scores, but not hospitalizations. However, a significant decrease in acute phase-reactants and immunoglobulins was observed at the one-year follow-up compared to baseline. Despite the relatively small cohort, the reported findings suggest that lung function impairment may not rely entirely on the patients' inflammatory status.

Systemic Profiles of microRNAs, Redox Balance, and Inflammation in Lung Cancer Patients: Influence of COPD.

Lung cancer (LC) risk increases in patients with chronic respiratory diseases (COPD). MicroRNAs and redox imbalance are involved in lung tumorigenesis in COPD patients. Whether systemic alterations of those events may also take place in LC patients remains unknown. Our objectives were to assess the plasma levels of microRNAs, redox balance, and cytokines in LC patients with/without COPD. MicroRNAs (RT-PCR) involved in LC, oxidized DNA, MDA-protein adducts, GSH, TEAC, VEGF, and TGF-beta (ELISA) were quantified in plasma samples from non-LC controls (n = 45), LC-only patients (n = 32), and LC-COPD patients (n = 91). In LC-COPD patients compared to controls and LC-only, MDA-protein adduct levels increased, while those of GSH decreased, and two patterns of plasma microRNA were detected. In both LC patient groups, miR-451 expression was downregulated, while those of microRNA-let7c were upregulated, and levels of TEAC and TGF-beta increased compared to the controls. Correlations were found between clinical and biological variables. A differential expression profile of microRNAs was detected in patients with LC. Moreover, in LC patients with COPD, plasma oxidative stress levels increased, whereas those of GSH declined. Systemic oxidative and antioxidant markers are differentially expressed in LC patients with respiratory diseases, thus implying its contribution to the pathogenesis of tumorigenesis in these patients.

Do Redox Balance and Inflammatory Events Take Place in Mild Bronchiectasis? A Hint to Clinical Implications.

We hypothesized that in mild bronchiectasis patients, increased systemic inflammation and redox imbalance may take place and correlate with clinical parameters. In plasma samples from patients with very mild bronchiectasis, inflammatory cells and molecules and redox balance parameters were analyzed. In the patients, lung function and exercise capacity, nutritional status, bacterial colonization, and radiological extension were assessed. Correlations between biological and clinical variables were determined. Compared to healthy controls, levels of acute phase reactants, neutrophils, IgG, IgA, myeloperoxidase, protein oxidation, and GSH increased and lung function and exercise capacity were mildly reduced. GSH levels were even greater in ex-smoker and Pseudomona-colonized patients. Furthermore, radiological extension inversely correlated with airway obstruction and, disease severity, and positively correlated with neutrophil numbers in mild bronchiectasis patients with no nutritional abnormalities. In stable patients with mild bronchiectasis, several important inflammatory and oxidative stress events take place in plasma. These findings suggest that the extension of bronchiectasis probably plays a role in the development of redox imbalance and systemic inflammation in patients with mild bronchiectasis. These results have therapeutic implications in the management of bronchiectasis patients.

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.

Estudio descriptivo sobre la influencia de la metodología en la medición de la fuerza inspiratoria máxima en nariz (SNIP) en población sana / Descriptive Study of the Effect of Methodology in the Measurement of Sniff Nasal Inspiratory Pressure (SNIP) in a Healthy Population

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Is iron deficiency modulating physical activity in COPD?

There is evidence that iron plays a key role in the adequate functioning of skeletal muscle. While it has been demonstrated that nonanemic iron deficiency (NAID) affects exercise tolerance and response to exercise training in patients with COPD, the impact on daily physical activities (DPAs) remains unknown. Eighteen COPD patients with NAID (ferritin <100 ng/mL or ferritin 100-299 ng/mL with a transferrin saturation <20%) and 18 COPD patients without this abnormality, matched for age, gender, and the degree of airflow limitation (control group), were enrolled to the study. The primary outcome was the level of DPA assessed by accelerometers. Patients were (mean [SD]) 66 (7) years and were mostly male (70%) and former smokers (52%). Their forced expiratory volume at 1 second was 41 (16)% predicted, carbon monoxide diffusing capacity was 47 (14)% predicted and oxygen arterial pressure reached 70 (11) mmHg. DPA and the number of steps per day were lower in NAID COPD patients compared with controls (physical activity level 1.39 vs 1.59, P<0.05; and 4,402 vs 6,975 steps/day, P<0.05, respectively). The percentage of patients with increased time spent sitting per day (>6 hours) was higher in patients with NAID compared with controls (73% vs 37%, P<0.05). In addition, the percentage of patients doing moderate to vigorous physical activity per day (>3 metabolic equivalents of task, at least 30 minutes) was lower in this group (66% vs 100%, P<0.05). The presence of iron deficiency was associated with reduced DPA in COPD patients. Further studies are needed to evaluate iron reposition and their impact on the level of physical activity in these patients.

Presión inspiratoria nasal: ¿una alternativa para la evaluación de la fuerza muscular inspiratoria? / Nasal inspiratory pressure: an alternative for the assessment of inspiratory muscle strength?

Introducción: La fuerza de los músculos inspiratorios se evalúa habitualmente en la clínica a través de ladeterminación de la presión estática máxima en boca (PIM). Sin embargo, esta maniobra presenta algunosproblemas, por lo que en los últimos años se han desarrollado diferentes alternativas como la mediciónde la presión inhalatoria nasal máxima (SNIP).Objetivo: Evaluar la determinación de SNIP como alternativa para la evaluación de la fuerza muscularinspiratoria.Método: Sujetos incluidos consecutivamente en tres grupos: control (8), EPOC (23) y neuromuscular(21). Se determinaron diferentes presiones inspiratorias máximas: (a) dinámica en esófago (sniffPesmáx,variable de referencia), (b) PIM, y (c) SNIP.Resultados: SNIP y PIM mostraron una buena correlación con sniffPesmáx (r = 0,835 y 0,752, respectivamente,en los controles, p < 0,05 ambas). La correlación intraclase SNIP/sniffPesmáx fue de 0,585 (IC95%: -0,097 a 0,901) en los controles, 0,569 (IC 95%: -0,048 a 0,836) en EPOC, y 0,840 (IC 95%: 0,459 a0,943) en enfermos neuromusculares. Estos valores fueron respectivamente de 0,602 (IC 95%: -0,108 a0,933), 0,418 (IC 95%: -0,108 a 0,761), y 0,712 (IC 95%: 0,378 a 0,882) para PIM/sniffPesmáx. La SNIP yla PIM mostraron una sensibilidad del 100% en los 3 grupos mencionados, aunque la especificidad erarespectivamente del 100, 69 y 75% para la SNIP, y 83, 54 y 75%, para la PIM.Conclusiones: La SNIP constituye un buen reflejo de la fuerza muscular inspiratoria. Probablemente supapel en la clínica sea complementario al de la PIM(AU)

Introduction: The strength of inspiratory muscles is assessed thorough the determination of the staticmouth pressure (MIP). However, since this manoeuvre has some problems, alternative techniques havebeen developed in the last few years. One of the most promising is determination of sniff nasal inspiratorypressure (SNIP).Aim: To evaluate SNIP assessment as an alternative for the evaluation of the maximal inspiratory musclestrength.Methods: Subjects were consecutively included and assigned to one of three different groups: control(8), COPD patients (23) and patients with neuromuscular disorders (21). Different maximal inspiratorypressures were determined: (a) dynamic at the esophagus (sniffPesmáx, reference variable), (b) MIP, and(c) SNIP.Results: Both SNIP and MIP showed an excellent correlation with the reference variable, sniffPesmáx(r=0.835 and 0.752, respectively, P<0.05 for both). SNIP/sniffPesmáx intra-class correlation coefficientswere 0.585 (CI 95%: -0.097 to 0.901) in controls, 0.569 (CI 95%: -0.048 to 0.836) inCOPDpatients, and 0.840 (CI 95%: 0.459 to 0.943) in neuromuscular disorders, respectively. For MIP/sniffPesmáx these values were0.602 CI 95%: -0.108 to 0.933), 0.418 (CI 95%: -0.108 to 0.761), and 0.712 (CI 95%:, 0.378 a 0.882). Moreover,both SNIP and MIP showed 100% sensitivity in the three groups of subjects, although specificities were100%, 69% and 75% for SNIP, and 83%, 54% and 75% for MIP, respectively.Conclusions: SNIP is a good physiological marker of inspiratory muscle strength. Its role is likely tocomplement that of MIP(AU)

Nasal inspiratory pressure: an alternative for the assessment of inspiratory muscle strength?

INTRODUCTION: Inspiratory muscle strength is usually assessed thorough the determination of static mouth pressure (PImax). However, since this manoeuvre presents certain problems, alternative techniques have been developed over the last few years. One of the most promising is determination of sniff nasal inspiratory pressure (SNIP). AIM: To evaluate SNIP assessment as an alternative for the evaluation of the inspiratory muscle strength. METHODS: Subjects were consecutively included and assigned to one of three different groups: control (8), COPD patients (23) and patients with neuromuscular disorders (21). Different maximal inspiratory pressures were determined: (a) dynamic in the esophagus (maximal sniff Pes, reference variable), (b) PImax, and (c) SNIP. RESULTS: Both SNIP and MIP showed an excellent correlation with Pes (r=0.835 and 0.752, respectively, P<0.05 for both). SNIP/Pes intra-class correlation coefficients were 0.585 (CI 95%: −0.097 to 0.901) in controls, 0.569 (CI 95%: −0.048 to 0.836) in COPD patients, and 0.840 (CI 95%: 0.459 to 0.943) in neuromuscular disorders, respectively. For PImax/Pes, these values were 0.602 CI 95%: −0.108 to 0.933), 0.418 (CI 95%: −0.108 to 0.761), and 0.712 (CI 95%: 0.378 a 0.882). Moreover, both SNIP and PImax showed 100% sensitivity in the three groups of subjects, although specificities were 100%, 69% and 75% for SNIP, and 83%, 54% and 75% for PImax, respectively. CONCLUSIONS: SNIP is a good physiological marker of inspiratory muscle strength. Its role is likely to complement that of PImax.