Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Platelet-to-Lymphocyte Ratio and Survival in Malignant Pleural Effusion.

BACKGROUND: Efforts have been made to search for parameters that facilitate the prediction of the 3-month survival for clinical decisions in patients with malignant pleural effusion (MPE). We sought to evaluate whether the platelet-to-lymphocyte ratio (PLR) may be a useful marker of 3-month survival in a series of consecutive patients with MPE. METHODS: A total of 81 patients with MPE were included, 46 (57%) of whom were female. Twenty-six patients (32%) died during the first 3 months according to thoracentesis data. RESULTS: The area under the receiver operating characteristics curve was 0.73 for PLR. Using a cutoff point of 158, patients with higher PLR values experienced higher mortality at 3 months (p = 0.001). CONCLUSIONS: PLR was able to successfully differentiate patients with different survival at 3 months. Outcomes of the PLR (a fast and inexpensive test) could be included among the prognostic factors able to guide the personalized management of MPE.

Prognostic Value of Hematological Inflammatory Markers in Patients with Pleural Effusion Due to Heart Failure.

BACKGROUND: Pleural effusions due to heart failure are associated with a high 1-year mortality. Several hematological parameters have been shown to provide prognostic information in patients with cardiovascular diseases. The objective was to assess whether hematological markers can also provide prognostic information in patients with pleural effusion caused by heart failure. METHODS: This was a retrospective study of patients with pleural effusion due to heart failure who underwent a diagnostic thoracentesis. The hematological parameters evaluated were as follows: neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, platelet count, platelet-to-lymphocyte ratio, mean platelet volume (MPV), and MPV-to-platelet ratio. Patients were divided into two groups: those who died within 1 year and survivors of more than 1 year. Differences and possible correlations were analyzed with non-parametric tests. Diagnostic values were estimated. Survival analysis was performed using the Kaplan-Meier method. Cox regression analysis was performed to identify independent variables. RESULTS: Twenty five of 55 (45%) patients died within 1-year from thoracentesis. Patients who died in this period were older, aged 83 years (73 - 87, median and interquartile range, IQR) vs. 74 (65 - 82); with lower platelet count: 181 x 103 (140 - 258 x 103) vs. 241 x 103 (198 - 324 x 103); and higher MPV/platelet: 48.1 (34.9 - 75.6) vs. 35.6 (27.1 - 42.9). In the regression analysis only the MPV/platelet had statistical significance (p = 0.002). MPV/platelet > 50 had a specificity of 87% for 1-year mortality, and a ratio > 30 had a sensitivity of 84%. CONCLUSIONS: Simple hematological parameters such as platelet count and MPV/platelet, may provide useful prognostic information for predicting 1-year mortality in patients with pleural effusion due to heart failure.

[Hyperlactatemia in hospitalized patients with asthma. Frequency and clinical implications]. / Hiperlactatemia en pacientes hospitalizados por asma. Frecuencia e implicaciones clínicas.

Increased levels of lactic acid have been described in patients treated for asthma exacerbation. However, the frequency and clinical significance of hyperlactatemia in real-world practice is unknown. The objective of the study was to evaluate the characteristics associated with hyperlactatemia in blood gas analysis of patients with asthma exacerbation hospitalized in a pulmonary department. This is a retrospective 3-year study (2015 to 2017) of patients discharged from the pulmonary department. The level of lactic acid in the blood gas test and the possible relationship with clinical, laboratory, therapy, spirometric values, hospitalization length and use of critical care resources were analyzed. A total of 112 patients with 182 admissions were included in the study. Thirty-two (29%) patients had hyperlactatemia in at least one blood gas analysis. Elevated lactic acid was observed in 42 of 182 admissions (23%), which had larger length hospital stay (median, 6 vs. 5 days, p = 0.013). Hyperlactatemia was present in 8 of 10 admissions in the critical care units, mainly after receiving bronchodilator therapy. There was a significant correlation between lactate level and bicarbonate level (r = -0.417, p = 0.003) and between lactate level and base excess (r = -0.484, p < 0.001) in cases with hiperlactatemia. Hyperlactatemia is a relatively frequent finding in blood gas analysis of patients hospitalized because of asthma (23% of admissions). These admissions with hiperlactatemia are associated with larger hospital length of stay.

[Cross-cultural adaptation to Spanish of the Perceived Sensitivity to Medicines scale]. / Adaptación transcultural al español de la Escala de Sensibilidad Percibida a los Medicamentos.

BACKGROUND AND OBJECTIVE: Patients' views regarding the actions and side effects of medicines can be measured with the Perceived Sensitivity to Medicines (PSM) scale. The aim of this study was to translate and adapt the PSM scale for use in the Spanish population. MATERIALS AND METHODS: The translation and cultural adaptation of the PSM scale and a pretest of the Spanish version were carried out with 50 patients receiving outpatient care in various specialties. RESULTS: There were no difficulties in the stages of the translation and adaptation process. In the cognitive interview, participants found the five items easy to understand (mean score of 3.86±0.24 out of 4). CONCLUSION: Given its brevity, the Spanish version of the PSM scale represents an easily applicable tool for both research and clinical purposes.

First evidence of microplastics isolated in European citizens' lower airway.

Microplastics (MPs) have been detected in all environmental locations, including the atmosphere. However, few studies have investigated the presence of airborne MPs in the human respiratory system. Our research purpose was to investigate these pollutants in the lower human airways of 44 adult European citizens, using bronchoalveolar lavage fluid (BALF) collection as a minimally invasive method, that enables the detection of these pollutants in living patients. We studied the relationship between the patients' life habits and physiological parameters, based on background information and medical and occupational history, and the concentration of MPs isolated from their respiratory systems. Our results indicate that most MPs were in the form of microfibers (MFs) (97.06%), with an average concentration of 9.18 ± 2.45 items/100 mL BALF, and only 5.88% (0.57 ± 0.27 items/100 mL BALF) were particulate MPs, without a significant relationship with environmental, physiological, or clinical factors. The average size was 1.73 ± 0.15 mm, with the longest dimension (9.96 mm) corresponding to a polyacrylic fiber. Taken together, the results demonstrated the occurrence of MPs in the lower human airway, although more studies are necessary to elucidate the negative effects these pollutants could induce in the human respiratory system and its associated diseases.

Comparison of the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in an in vitro experimental model.

OBJECTIVES: To compare the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in the latent and exponential growth phases. METHODS: Ciprofloxacin, levofloxacin and moxifloxacin were tested against 16 M. tuberculosis clinical isolates (4 resistant and 12 susceptible to fluoroquinolones) from Elche, Spain, isolated between 1992 and 2009. To study bactericidal activity, an inoculum of approximately 10(5) cfu of each isolate was cultured in Middlebrook 7H9 broth. The broth was previously acidified to pH 4.6 to obtain the microorganism in the stationary phase. Cultures with different concentrations (0.1 to 50 mg/L) of antibiotic and antibiotic-free controls were incubated for 48 h then plated onto Middlebrook 7H11 to detect bacterial killing. In all stages of the process the M. tuberculosis strain ATCC 41323 was included as a quality control to ensure reproducible results. RESULTS: Moxifloxacin and levofloxacin were found to exhibit bactericidal activity at lower concentrations and against more strains in both the latent and the exponential growth phases compared with ciprofloxacin. The bactericidal activity of moxifloxacin was greater than that of levofloxacin against microorganisms in the exponential growth phase, but the opposite was true in the latent phase. CONCLUSIONS: Our data confirm the usefulness of moxifloxacin in the treatment of tuberculosis and suggest that levofloxacin may be used as an alternative drug in the treatment of latent tuberculosis when it is not possible to use isoniazid. Based on the results presented, ciprofloxacin appears to be a poor choice.

Identification of bacterial DNA in noninfectious pleural fluid with a highly sensitive PCR method.

BACKGROUND: Bacterial DNA due to bacterial translocation has been identified in noninfectious ascitic fluid samples. OBJECTIVE: This study investigated the possible presence of bacterial DNA in the pleural fluid of patients with pleural effusions of noninfectious origin, using a highly sensitive PCR-based method. METHODS: Pleural fluid samples from 175 patients (average age ± SD: 69 ± 14 years) with noninfectious pleural effusion (62 transudates, 113 exudates) were analyzed. Bacterial DNA was detected using nested PCR with amplification of a fragment of the gene r16S, with 2 amplification protocols, i.e. low sensitivity (10 and 40 cycles) and high sensitivity (40 and 40 cycles). RESULTS: With the less sensitive amplification process, only 1 sample was positive (Haemophilus parainfluenzae in a patient with hepatic hydrothorax). With the highly sensitive nested PCR method, bacterial DNA was identified in the pleural fluid, of both transudative and exudative origin, of 75 of the 175 patients (43%). In cases of isolation of a single bacterium, the more frequent were Escherichia coli, Salmonella enterica and Streptococcus pneumoniae. CONCLUSIONS: Regardless of its origin, bacterial DNA can be identified in almost half of noninfectious pleural effusions by using a highly sensitive PCR-based method. The possible clinical significance or prognostic value of these findings deserves to be evaluated.

Prediction of three-month readmission based on haematological parameters in patients with severe COPD exacerbation.

INTRODUCTION: Approximately one-third of patients hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD) are readmitted to the hospital within 90 days. It is of interest to identify biomarkers that predict relapse in order to prevent readmission in these patients. In our prospective study of patients admitted for COPD exacerbation, we aimed to analyse whether routine haematological parameters can help predict the three-month readmission risk. MATERIAL AND METHODS: 106 patients were included, of whom 23 were female (22%). The age (mean ± SD) was 73 ± 10 years, and the forced expiratory volume in 1 second (FEV1) was 44 ± 15%. The haematological parameters were obtained from the first blood test result during admission. The variables were as follows: red cell distribution width, mean platelet volume (MPV), platelet (PLT) count, neutrophil to lymphocyte ratio, PLT to lymphocyte ratio, MPV to PLT ratio, and eosinophil count. Patients were differentiated into two groups for each haematological parameter according to median value, and the percentage of readmissions in each of the groups was recorded. RESULTS: Twenty-five patients (24%) were readmitted to hospital within three months of discharge. Only the difference in low-MPV and high-MPV patients was significant (37% vs 10%, p = 0.001). The predictive capacity for three-month readmission measured by the area under the curve (AUC) did not show clinically applicable values; the best result was for MPV (AUC 0.64). In the remaining values, the AUC was between 0.52 and 0.55. CONCLUSION: Routine haematological parameters proposed as prognostic biomarkers in COPD obtained at the moment of hospital admission were not useful for predicting three-month readmission.

[Sarcopenia index in hospitalized patients with chronic obstructive pulmonary disease exacerbation]. / Índice de sarcopenia en pacientes hospitalizados por agudización de la enfermedad pulmonar obstructiva crónica.

Sarcopenia (loss of muscle mass and function) implies a worse prognosis. However, its diagnosis is complex and is not made in routine clinical care. A biomarker has been proposed as a surrogate estimator of skeletal muscle mass, the so-called sarcopenia index ([serum creatinine/cystatine C] x100) which is associated with prognostic features in various diseases including patients with stable chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate the potential clinical and prognostic information of this biomarker in COPD exacerbation. This is a one-year prospective study of consecutive patients admitted for COPD exacerbation. A total of 89 patients, 70 men (79%) and 19 women (21%) were included. Those with lower values of the sarcopenia index had a higher level of dyspnoea and a longer hospitalization. In the correlation analysis, the index had statistically significant values with FEV1 (r = 0.23), PaCO2 (r = -0.30), bicarbonate (r = -0.31), dyspnoea (r = -0.25) and length of admission (r = -0.30). In patients admitted for COPD exacerbation, the sarcopenia index was related to prognostic characteristics, so that lower values were associated with longer duration of hospital admission, more dyspnoea and greater functional impairment. As this is an index associated with muscle mass, its determination may identify patients who could be the subject of a differentiated therapeutic plan.

La presencia de sarcopenia (pérdida de masa y función muscular) implica peor pronóstico. Sin embargo, su diagnóstico es complejo y no se realiza en la atención clínica habitual. Se ha propuesto un biomarcador como estimador subrogado de la masa muscular esquelética, el denominado índice de sarcopenia ([creatinina sérica/cistatina C] x100) que se asocia a características pronósticas en diversas enfermedades incluyendo pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable. El objetivo de nuestro estudio ha sido evaluar de forma prospectiva la potencial información clínica y pronóstica de este biomarcador en agudización de la EPOC. Se trata de un estudio prospectivo, durante un año, de los pacientes consecutivos que ingresan por agudización de su EPOC. Se incluyeron 89 pacientes, 70 varones (79%) y 19 mujeres (21%). Aquellos con valores disminuidos del índice de sarcopenia tenían más disnea y requerían una internación más prolongada. En el análisis de correlación se obtuvo valores con significación estadística del índice con FEV1 (r = 0.23), PaCO2 (r = -0.30) y bicarbonato (r = -0.31), y con la disnea (r = -0.25) y la duración del ingreso (r =- 0.30). En los ingresados por agudización de la EPOC el índice de sarcopenia se relacionó con características pronósticas, de modo que los valores inferiores se asociaron a mayor duración de la internación, más disnea y mayor afectación funcional. Al tratarse de un índice asociado a la masa muscular, su determinación podría identificar a pacientes a incluir en un plan terapéutico diferenciado.

Symptoms in patients with asthma infected by SARS-CoV-2.

INTRODUCTION: Organ tropism of SARS-CoV-2 to the respiratory tract could potentially aggravate asthma. The susceptibility of patients with asthma to develop an exacerbation when they are infected with SARS-CoV-2 is unknown. We aimed to investigate the symptoms presented in patients with asthma who became infected with SARS-CoV-2. METHODS AND RESULTS: All patients over 14 years of age who tested positive for SARS-CoV-2 (by RT-PCR) were included (n = 2995). In patients with asthma (n = 77, 2.6%; 44 females), symptoms, therapy and phenotype were recorded. Seventeen (22%) patients had mild asthma, 55 (71%) moderate and five severe (6%). Twenty-six patients with asthma (34%) were asymptomatic, 34 (44%) developed symptoms but did not require hospital admission, and 17 (22%) were hospitalised. One patient was admitted because of asthma exacerbation without pneumonia or other symptoms. Ten patients (13%) had wheezes (six with pneumonia). Comparison of wheezing between patients with non-T2 asthma and the rest of the patients was statistically significant, (p < 0.001). CONCLUSIONS: SARS-CoV-2 infection is not a significant cause of asthma exacerbation, although some patients may present wheezing, especially in cases of pneumonia. The severity of asthma does not seem to be associated with symptoms of the disease.

Asthma prevalence in patients with SARS-CoV-2 infection detected by RT-PCR not requiring hospitalization.

INTRODUCTION: The prevalence of asthma in patients hospitalized with SARS-CoV-2 has been studied and varies widely in the different series. However, the prevalence in SARS-infected patients not requiring hospitalization is not known. The objective of this study was to analyze the presence of asthma in a consecutive series of patients who tested positive in the RT-PCR assay for SARS-CoV-2 and did not require hospital admission. METHODS AND RESULTS: A total of 218 patients (58% of those who tested positive) did not require hospitalization; they had a median age of 45 years (IQR 34-57) and 57% were female. Six patients (2.8%) had a previous diagnosis of asthma. Only one patient developed a mild aggravation of asthma symptoms associated with SARS-CoV-2 infection. CONCLUSIONS: Few patients with asthma were infected by SARS-CoV-2, and this infection was not a significant cause of asthma exacerbation.

Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19.

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.