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.

Validation of the Spanish Activity Questionnaire in COPD (SAQ-COPD) in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The Spanish Activity Questionnaire in COPD (SAQ-COPD) is a short, simple physical activity (PA) measurement instrument for patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed its validity and sensitivity to change. Methods: Prospective scale validation study. An accelerometer (DynaPort MoveMonitor®) and the Yale Physical Activity Survey (YPAS) were used as reference standards. The analyses examined the criterion validity (Spearman correlations), internal consistency (Cronbach's alpha), factorial structure, test-retest reliability (intraclass correlation coefficient, ICC), sensitivity to change and receiver operating characteristic (ROC) curve to classify patients with low PA. Results: A total of 300 patients diagnosed with COPD were analyzed (73% males, mean age 66 ± 8 years, 40.3% with severe airflow limitation). Cronbach's alpha was 0.60 and Spearman's correlations with accelerometer measurements of PA [number of steps, metabolic equivalents (MET), physical activity level (PAL)] and YPAS ranged from 0.37 to 0.53 (all p < 0.001). ICC was 0.69 (95% CI 0.61-0.74) and the area under the ROC curve to identify low PA was 0.65 (95% confidence interval: 0.58-0.73). Significant variations in SAQ-COPD scores were found between groups defined by YPAS for change. Conclusion: The SAQ-COPD questionnaire is a valid instrument for classifying PA in patients with COPD. Correlations with other instruments provide criterion validity and also demonstrate good sensitivity to change.

Creation of the SAQ-COPD Questionnaire to Determine Physical Activity in COPD Patients in Clinical Practice. / Creación del cuestionario SAQ-COPD (Spanish Physical Activity Questionnaire in COPD) para la medida de la actividad física de pacientes con EPOC en la práctica clínica.

INTRODUCTION: Physical activity (PA) is a significant clinical dimension in COPD, but no useful tools are available to determine this variable in routine clinical practice. OBJECTIVE: To create a simple, easy-to-use, specific questionnaire to detect PA deficits. METHOD: A multidisciplinary panel of COPD experts was formed to review PA, its determinants, and measuring methods. The methodology for selecting specific dimensions and items was agreed in rounds, and the aspects to be included in the preliminary version were determined. The questionnaire structure was defined according to applicability of these aspects in clinical practice. Agreements were reached by consensus of the members. RESULTS: A total of 148 items were reviewed, of which only 3 were directly selected. It was decided that the questionnaire should evaluate the intensity (low, moderate, or intense), amount, and frequency of PA, and inactivity or sedentary lifestyles. It also gathers information on the profile of inactive patients, and includes a measure of impact, defined as the patient's perception of their expectations regarding activity, their personal experience, characteristics of their environment, and their personality. The questionnaire is divided into 2blocks, one aimed at quantifying PA, and the other at collecting data for defining the profile and impact in patients with low PA only. CONCLUSION: The SAQ-COPD is a simple, short, specific questionnaire, designed to evaluate PA in COPD patients in clinical practice.

Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC-QTOF-MS/MS platform.

Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n = 25) or without (n = 32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection.

Non-invasive monitoring of diaphragmatic timing by means of surface contact sensors: an experimental study in dogs.

BACKGROUND: Non-invasive monitoring of respiratory muscle function is an area of increasing research interest, resulting in the appearance of new monitoring devices, one of these being piezoelectric contact sensors. The present study was designed to test whether the use of piezoelectric contact (non-invasive) sensors could be useful in respiratory monitoring, in particular in measuring the timing of diaphragmatic contraction. METHODS: Experiments were performed in an animal model: three pentobarbital anesthetized mongrel dogs. The motion of the thoracic cage was acquired by means of a piezoelectric contact sensor placed on the costal wall. This signal is compared with direct measurements of the diaphragmatic muscle length, made by sonomicrometry. Furthermore, to assess the diaphragmatic function other respiratory signals were acquired: respiratory airflow and transdiaphragmatic pressure. Diaphragm contraction time was estimated with these four signals. Using diaphragm length signal as reference, contraction times estimated with the other three signals were compared with the contraction time estimated with diaphragm length signal. RESULTS: The contraction time estimated with the TM signal tends to give a reading 0.06 seconds lower than the measure made with the DL signal (-0.21 and 0.00 for FL and DP signals, respectively), with a standard deviation of 0.05 seconds (0.08 and 0.06 for FL and DP signals, respectively). Correlation coefficients indicated a close link between time contraction estimated with TM signal and contraction time estimated with DL signal (a Pearson correlation coefficient of 0.98, a reliability coefficient of 0.95, a slope of 1.01 and a Spearman's rank-order coefficient of 0.98). In general, correlation coefficients and mean and standard deviation of the difference were better in the inspiratory load respiratory test than in spontaneous ventilation tests. CONCLUSION: The technique presented in this work provides a non-invasive method to assess the timing of diaphragmatic contraction in canines, using a piezoelectric contact sensor placed on the costal wall.

Protein tyrosine nitration in the ventilatory muscles: role of nitric oxide synthases.

Modification of tyrosine residues and formation of 3-nitrotyrosine is one of the most commonly identified effects of reactive nitrogen species on proteins. In this study we evaluated the presence and localization of tyrosine nitration in various ventilatory and limb muscles. We also assessed the contribution of the neuronal (nNOS), the endothelial (eNOS), and the inducible (iNOS) isoforms of nitric oxide synthase (NOS) to tyrosine nitration in skeletal muscles both under normal conditions and in response to severe sepsis. In normal rats and mice, muscle tyrosine nitration was detected at 52, 48, 40, 30, 18, and 10 kD protein bands. Tyrosine nitration of the majority of these protein bands was significantly reduced within 1 h of in vivo NOS inhibition in rats. Diaphragmatic protein tyrosine nitration in mice deficient in the inducible NOS (iNOS-/-) averaged ~ 50% of that detected in wild-type (iNOS+/+) mice. Injection of bacterial lipopolysaccharides (LPS) in rats produced a significant rise in protein tyrosine nitration in the mitochondrial and membrane fractions but not in the cytosol of ventilatory muscles. Absence of iNOS expression (iNOS-/-), but not nNOS (nNOS-/-) or eNOS (eNOS-/-), in genetically altered mice resulted in a significant reduction in LPS-mediated rise in diaphragmatic nitrotyrosine. We conclude that tyrosine nitration of proteins occurs in normal muscle fibers and is dependent mainly on the activity of the iNOS isoform. Sepsis-mediated increase in protein tyrosine nitration is limited to the mitochondria and cell membrane and is highly dependent on the activity of the iNOS but not the nNOS or eNOS isoforms.