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PURPOSE: The aim of this study was to determine how sodium hydrogen carbonate (NaHCO3) ingestion during a 1-h recovery period after a 200-m front-crawl swim affects blood-gas levels, acid-base balance, and performance during a successive trial. METHODS: Fourteen national-level male swimmers (age: 21 ± 3 years, body mass (BM):77 ± 10 kg, stature: 181 ± 7 cm) performed four maximal 200-m front-crawl tests. On one of the two days, the swimmers swam two 200-m tests with a 1-h recovery break, during which they drank water (WATER); on the other day, they performed the same protocol but consumed 0.3 g min-1 NaHCO3 solution during the recovery break (NaHCO3). RESULTS: The ingestion of NaHCO3 before the second test had no effect on swim time despite a greater [ HCO 3 - ] (19.2 ± 2.3 mmol L-1) than that measured during the first test (NaHCO3) (14.5 ± 1.1 mmol L-1) and the other two tests (WATER) (12.7 ± 2.4 and 14.8 ± 1.5 mmol L-1; F = 18.554; p = 0.000) and a higher blood pH (7.46 ± 0.03) than that measured during the first test (NaHCO3) (7.39 ± 0.02) and the other two tests (WATER) (7.16 ± 0.04 and 7.20 ± 0.05); (F = 5.255; p = 0.004). An increase in blood pCO2 (0.2 ± 0.3 kPa) between both tests (NaHCO3) compared to unchanged pCO2 values (- 0.1 ± 0.3 kPa) between the other two tests (WATER) (t = - 2.984; p = 0.011; power = 0.741) was confirmed. CONCLUSIONS: NaHCO3 ingestion during the recovery period between two 200-m front-crawl time trials had a strong buffering effect that did not positively affect performance. An increase in pCO2 may have counterbalanced this impact.
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Background: The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods: A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results: Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterised by a very low risk of mortality. Conclusions: By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown. METHODS: In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data. RESULTS: HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival. CONCLUSIONS: Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
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Episodes of acute exacerbations are major drivers of hospitalisation and death from COPD. To date, there are no objective biomarkers of disease activity or biomarkers to predict patient outcome. In this study, 211 patients hospitalised for an acute exacerbation of COPD have been included. At the time of admission, routine blood tests have been performed including complete blood count, C-reactive protein, cardiac troponin T and NT-proBNP. Heat shock protein 27 (HSP27) serum concentrations were determined at time of admission, discharge and 180 days after discharge by ELISA. We were able to demonstrate significantly increased HSP27 serum concentrations in COPD patients at time of admission to hospital as compared to HSP27 concentrations obtained 180 days after discharge. In univariable Cox regression analyses, a HSP27 serum concentration ≥ 3098 pg/mL determined at admission was a predictor of all-cause mortality at 90 days, 180 days, 1 year and 3 years. In multivariable analyses, an increased HSP27 serum concentration at admission retained its prognostic ability with respect to all-cause mortality for up to 1-year follow-up. However, an increased HSP27 serum concentration at admission was not an independent predictor of long-term all-cause mortality at 3 years. Elevated serum HSP27 concentrations significantly predicted short-term mortality in patients admitted to hospital with acute exacerbation of COPD and could help to improve outcomes by identifying high-risk patients.
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Proteína C-Reactiva/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Biomarcadores/sangre , Femenino , Hospitalización/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Humanos , Masculino , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
BACKGROUND: The environment in swimming pools, which contain chlorine, might interact with the airway epithelium, resulting in oxidative stress and/or inflammation during high intensity training periods. METHODS: We evaluated pulmonary functional (metacholine challenge test, FEV1 and VC), cellular (eosinophils and neutrophils), inflammatory (FeNo, IL-5, IL-6, IL-8 and TNF-α), oxidative (8-isoprostanes) and angiogenesis factors (VEGF) in induced sputum and peripheral blood of 41 healthy non-asthmatic elite swimmers (median 16 years) during the period of high intensity training before a national championship. The second paired sampling was performed seven months later after training had been stopped for one month. RESULTS: There was a ten-fold increase (median 82-924â¯pg/ml; Pâ¯<â¯0.001) in 8-isoprostanes in induced sputum and five-fold increase (median 82-924â¯pg/ml; Pâ¯<â¯0.001) in sera during training in comparison to the period of rest. However, there was no difference in FEV1 (113 vs 116%), VC (119 vs 118%), FeNo (median 34 vs 38â¯ppb), eosinophils (2.7 vs 2.9% in sputum; 180 vs 165â¯cells/µl in blood), neutrophils, different cytokines or VEGF in induced sputum or sera. The only exception was TNF-α, which was moderately increased in sera (median 23 vs 40â¯pg/ml; Pâ¯=â¯0.02) during the peak training period. Almost half (18 of 41) of swimmers showed bronchial hyperresponsiveness during the peak training period (PC20 cutoff was 4â¯mg/ml). There was no correlation between hyperresponsiveness and the markers of oxidative stress or inflammation. CONCLUSIONS: High intensity training in healthy, non-asthmatic competitive swimmers results in marked oxidative stress at the airway and systemic levels, but does not lead to airway inflammation. However, we could not confirm that oxidative stress is associated with bronchial hyperresponsiveness (AHR), which is often observed during the peak exercise training period.
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Pruebas de Provocación Bronquial/métodos , Cloro/efectos adversos , Inflamación/inmunología , Estrés Oxidativo/fisiología , Natación/fisiología , Adolescente , Hiperreactividad Bronquial/fisiopatología , Niño , Dinoprost/análogos & derivados , Dinoprost/sangre , Exposición a Riesgos Ambientales/efectos adversos , Eosinófilos/inmunología , Femenino , Humanos , Inflamación/sangre , Masculino , Neutrófilos/inmunología , Estudios Prospectivos , Pruebas de Función Respiratoria/métodos , Esputo/metabolismo , Piscinas , Enseñanza , Adulto JovenRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. METHODS: This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). RESULTS: Overall, 41 patients (mean age 61 ± 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). CONCLUSIONS: In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.
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BACKGROUND: We aimed to assess the relationship between echocardiographic characteristics and mortality in patients with chronic obstructive pulmonary disease (COPD). METHODS: We prospectively studied 154 patients (mean age 71 ± 10 years, 71% male) with COPD. All patients underwent transthoracic Doppler echocardiography within 48 hours of hospital admission. Primary endpoint was all-cause mortality during a median period of 22 months. RESULTS: Mildly elevated tricuspid regurgitation pressure and mitral E/e' ratio were the most commonly encountered echocardiographic abnormalities, observed in 60% and 56% of patients, respectively. In Kaplan-Meier analysis of survival, left atrial enlargement, E/e' ratio > 8, right atrial enlargement, right ventricular dilation, decreased tricuspid annular plane systolic excursion, decreased tricuspid annular systolic velocity, and elevated tricuspid regurgitation velocity were associated with all-cause mortality (p < 0.05 for all). In the Cox proportional hazards analysis, the mitral E/e' ratio (hazard ratio 1.048; 95% confidence interval 1.001-1.096) remained an independent echocardiographic predictor of survival after adjustment for age, COPD severity, and other baseline echocardiographic parameters. CONCLUSIONS: Among patients with COPD, an abnormal mitral E/e' ratio was an independent echocardiographic predictor of all-cause mortality. Echocardiographic evaluation of structural and functional cardiac abnormalities provides important prognostic information and should be used routinely in the assessment of patients with COPD. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:211-221, 2017.
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Ecocardiografía Doppler/métodos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/fisiopatología , Disfunción Ventricular/diagnóstico por imagen , Disfunción Ventricular/fisiopatología , Anciano , Femenino , Estudios de Seguimiento , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Estimación de Kaplan-Meier , Masculino , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Eslovenia , Volumen Sistólico/fisiología , Insuficiencia de la Válvula Tricúspide/complicaciones , Disfunción Ventricular/complicacionesRESUMEN
Diagnosing heart failure with preserved ejection fraction (HFpEF) in patients with chronic obstructive pulmonary disease (COPD) is difficult due to overlapping pathophysiological pathways, risk factors and clinical presentations. We investigated the prevalence and prognostic implications of coexisting HFpEF in patients hospitalized for acute exacerbation of COPD. A total of 116 consecutive patients with an acute exacerbation of COPD were evaluated for HFpEF and followed for an average period of 22 ± 9 months for the occurrence of death from any cause. HFpEF was diagnosed in 22 (19 %) patients with COPD, who were older, and also had higher LV mass, left atrial size, and mitral E/Ea ratio than those without HFpEF (p < 0.05 for all comparisons). HFpEF was not independently associated with all-cause mortality [hazard ratio (HR) 1.07, 95 % confidence interval (CI) 0.44-2.62]. Global initiative for chronic Obstructive Lung Disease (GOLD) stage (IV vs. I-III, HR 2.37, CI 1.23-4.59) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (HR 2.79, CI 1.12-6.98) were independent predictors of long-term survival. HFpEF is present in one-fifth of patients with exacerbated COPD. Non-invasively diagnosed HFpEF may not be an independent predictor of all-cause mortality. Elevated NT-proBNP levels and very severe COPD were independently associated with unfavorable overall survival.
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Insuficiencia Cardíaca/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Biomarcadores/sangre , Ecocardiografía , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Masculino , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Pruebas de Función Respiratoria , Factores de Riesgo , Volumen Sistólico/fisiología , Tasa de SupervivenciaRESUMEN
OBJECTIVES: To test whether coordination of discharge from hospital reduces hospitalizations in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Randomized controlled clinical trial. SETTING: Specialized pulmonary hospital. PARTICIPANTS: Patients hospitalized for an acute exacerbation of COPD. INTERVENTION: Care as usual included routine patient education, supervised inhaler use, respiratory physiotherapy, and disease-related communication. The discharge coordinator intervention added assessment of patient situation and homecare needs. Patients and caregivers were actively involved and empowered in the discharge planning process, which was communicated with community medical professionals to provide continuity of care at home. MEASUREMENTS: The primary end-point of the study was the number of patients hospitalized because of worsening COPD. Key secondary end-points were time-to-COPD hospitalization, all-cause mortality, all-cause hospitalization, days alive and out of hospital, and health-related quality of life. RESULTS: Of 253 eligible patients (71 ± 9 years, 72% men, 87% GOLD III/IV), 118 were assigned to intervention and 135 to usual care. During a follow-up of 180 days, fewer patients receiving intervention were hospitalized for COPD (14% versus 31%, P = .002) or for any cause (31% versus 44%, P = .033). In time-to-event analysis, intervention was associated with lower rates of COPD hospitalizations (P = .001). A Cox model of proportional hazards, adjusted for sex, age, GOLD stage, heart failure, malignant disease, and long-term oxygen treatment, demonstrated that intervention reduced the risk of COPD hospitalization (hazard ratio 0.43, 95% confidence interval 0.24-0.77, P = .002). CONCLUSION: Among patients hospitalized for acute COPD exacerbation, discharge coordinator intervention reduced both COPD hospitalizations and all-cause hospitalizations.
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Manejo de Caso , Hospitalización/estadística & datos numéricos , Alta del Paciente , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Femenino , Servicios de Atención a Domicilio Provisto por Hospital , Hospitales Especializados , Humanos , Masculino , Evaluación de Necesidades , Educación del Paciente como Asunto , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/mortalidadRESUMEN
PURPOSE: In chronic obstructive pulmonary disease (COPD), cardiovascular system is involved but less is known about role of specific cardiac biomarkers. We aimed to investigate associations between N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T during hospitalisation with 6-month outcome. METHODS: This was a prospective study conducted in consecutive patients hospitalized for an acute exacerbation of COPD. On admission, and at discharge, NT-proBNP and troponin T were measured, and echocardiography was performed. Hospitalisations and mortality were recorded for 6 months after discharge. RESULTS: We included 127 patients (70 ± 10 years, 70% men, GOLD III/IV 87%). Left ventricular dysfunction was detected in 70 (55%) patients and diastolic dysfunction was the most common type (53 patients-42%). NT-proBNP and troponin T were elevated on admission in 60% and 36%, and at discharge in 28% and 19% of patients. During follow-up, 53 (42%) patients were hospitalized and 17 (13%) patients died. In Kaplan Meier analysis of survival curves, NT-proBNP on admission distinguished between deceased and surviving patients (p=0.011) whilst troponin T at discharge separated hospitalized and non-hospitalized patients (p=0.017). The adjusted Cox proportional hazard model confirmed these findings: discharge troponin T predicted hospitalisations (hazard ratio 2.89, 95% confidence interval 1.13-7.36) and admission NT-proBNP predicted mortality (hazard ratio 4.20, 95% confidence interval 1.07-14.01). CONCLUSIONS: Elevated NT-proBNP at discharge and troponin T on admission predict outcome in patients hospitalized for an acute exacerbation of COPD.
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Cardiopatías/sangre , Cardiopatías/diagnóstico , Hospitalización/tendencias , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Cardiopatías/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Thoracic ultrasound may be helpful in differentiating between malignant and tuberculosis-associated pleural exudate. This study aimed to evaluate its utility in patients with unexplained pleural exudate. METHODS: Consecutive patients were screened and pleural effusion was found in 278 patients. Pleural exudate was present in 106 patients and remained undiagnosed after biochemical and cytological evaluation in 40 patients (median age 58 years, 67% men) who then underwent detailed thoracic ultrasound for the presence of complex (septated or fibrous) or anechoic patterns. Pleural needle biopsy or thoracoscopy with histological evaluation were used for definitive diagnosis. RESULTS: History, clinical characteristics and routine procedures including cytology were not helpful in differential diagnosis. Pleural specimens for histological evaluation were obtained from all 40 patients and confirmed tuberculosis in 12 patients, cancer in nine and nonspecific pleuritis in 19. Sonographic finding of a complex septal pattern was present only in patients with tuberculosis (positive predictive value 100%); anechoic appearance was suggestive of nonspecific pleuritis (positive predictive value 65%). CONCLUSIONS: Thoracic ultrasound is a useful bedside method for differentiation of the etiology of pleural exudate. When a complex septal pattern is found, pleural needle biopsy should be the next diagnostic procedure, whereas with less complex pleural sonography findings other methods should be pursued.
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Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pleurales/diagnóstico por imagen , Derrame Pleural/diagnóstico por imagen , Adulto , Anciano , Biomarcadores/sangre , Biopsia con Aguja , Diagnóstico Diferencial , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Recuento de Leucocitos , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pleura/diagnóstico por imagen , Pleura/patología , Enfermedades Pleurales/patología , Derrame Pleural/etiología , Derrame Pleural/patología , Derrame Pleural Maligno/diagnóstico por imagen , Neoplasias Pleurales/diagnóstico por imagen , Neoplasias Pleurales/patología , Pleuresia/diagnóstico por imagen , Pleuresia/patología , Sistemas de Atención de Punto , Estudios Prospectivos , Eslovenia , Toracoscopía , Tuberculosis Pleural/diagnóstico por imagen , Tuberculosis Pleural/patología , UltrasonografíaRESUMEN
This report describes congenital coronary artery fistula of the right coronary artery draining into the left atrium in a young woman. The initial diagnosis of this rare anomaly was made noninvasively by echocardiography. Transesophageal echocardiography was vastly superior to transthoracic echocardiography in presenting the entire course of the fistula. The diagnosis was confirmed by coronary angiography. The fistula was successfully closed surgically.