Eduardo Garcia-Pachon

C-Reactive Protein in Lymphocytic Pleural Effusions: A Diagnostic Aid in Tuberculous Pleuritis

Background:C-reactive protein (CRP) pleural fluid levels have been found to be higher in tuberculosis and parapneumonic effusions than in other causes of pleural effusion. Objective:The aim of this study was to analyze whether CRP (a simple and inexpensive test) may be a diagnostic aid for tuberculosis in lymphocytic pleural effusions. Methods:One hundred and forty-four patients with a lymphocytic pleural effusion (more than 50% lymphocytes in the differential white blood cell count) were included. The patients were 93 men (65%) and 51 women (35%), aged 64 ± 18 years (mean ± SD). The diagnoses were as follows: tuberculosis, 20; pleural effusion associated with malignancy, 69; transudates, 38; other benign exudates, 17. Results: The CRP pleural fluid level was higher in tuberculous pleuritis (54 ± 24 mg/l) than in lymphocytic effusions of other origin (21 ± 16 mg/l; p < 0.001). High CRP levels (≧50 mg/l) have a high specificity for tuberculosis (95%), and low levels (<30 mg/l) have a high sensitivity (95%) for excluding disease. Conclusions: CRP pleural fluid level determination is useful in the diagnostic workup of lymphocytic pleural effusions. High CRP levels are very suggestive of tuberculous pleuritis, and low CRP levels make this diagnosis unlikely.

Sputum microbiota in moderate versus severe patients with COPD

To the Editor: The emergence of new massive sequencing methods has proved revolutionary for the study of complex microbial populations such as the microbiota of the respiratory tract in patients with chronic obstructive pulmonary disease (COPD) [1]. Using this powerful methodology, our objective was to compare the microbiota in two groups of patients with COPD of different severity in order to detect potential microbiological markers that could help to provide a better understanding of the pathogenesis of this disease and the role played by the microbiota in its severity. The current study recruited nine patients with mild or moderate COPD and 10 patients with severe or very severe COPD in a stable condition (at least 3 months without exacerbation or use of antibiotics for any other reason). Diagnosis and classification of COPD was established according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations [2]. After DNA extraction from good quality expectorated sputum, quantitative (q)PCR (7500 real time PCR system thermocycler; Life Technologies, Grand Island, NY, USA) was used to quantify the copy number of the 16S rRNA gene in each sample (total bacterial load), yielding a 468 bp amplicon located between nucleotides 340–808 in reference to the 16S rRNA gene of Escherichia coli strain MG1655 (National Center for Biotechnology Information (NCBI) reference sequence: NR_102804.1). In order to compare the results obtained, they were normalised to the number of human cells in the sample, quantified by qPCR, using the human albumin gene [3]. A region measuring 525 bp, between position 8 and 533 of the 16S rRNA gene was amplified and pyrosequenced (Roche GS FLX Titanium with Lib-L type microspheres; 454 Life Sciences, Branford, CT, USA). This region comprises the regions of gene hypervariability from V1 to V3 of the 16S rRNA gene …

El factor de impacto y el índice h de las revistas biomédicas españolas

El ı́ndice de factor de impacto (FI) se utiliza desde hace décadas para valorar la calidad de las revistas cientı́ficas. Se elabora con las revistas de la base de datos de Web of Science (WoS) de Thomson Scientific, y se publica anualmente en el Journal Citation Reports. El IF se calcula con el número de citaciones que recibe en un año una determinada revista en los 2 años precedentes en las publicaciones indexadas en la WoS, y este número se divide por el de artı́culos citables publicados en la revista evaluada. Sin embargo, existen numerosas crı́ticas a este ı́ndice, por ejemplo, que se incluyen citaciones a artı́culos que no se usan en el denominador de la fórmula (editoriales, revisiones de libros), que el perı́odo de evaluación es muy breve o que no se tiene en cuenta la calidad de las fuentes citadoras. En 2005, Hirsch propuso un nuevo ı́ndice como criterio para cuantificar la producción cientı́fica de un investigador. Se define este ı́ndice h como el número (h) de artı́culos de un autor que han recibido al menos h citas. Ası́, por ejemplo, si un autor ha publicado 10 artı́culos, y de ellos, 4 han recibido 4 o más citas y los otros 6 menos de 4 citas, su ı́ndice h será 4. Este ı́ndice ha tenido una muy rápida aceptación porque, a pesar de su simplicidad, tiene numerosas ventajas con respecto a otras propuestas, ya que se basa tanto en la productividad como en la importancia de los artı́culos reconocida por sus citas por otros autores, es robusto y poco manipulable. El cálculo del ı́ndice h fue pronto incluido en la WoS, proveedor de otros ı́ndices, como el factor de impacto. El ı́ndice h no se ha utilizado solo para la medida de la producción de investigadores individuales, sino que también se emplea en la evaluación de grupos de investigadores, organismos cientı́ficos, paı́ses y revistas. Fue en 2006 cuando Braun et al. propusieron aplicar el ı́ndice h al análisis bibliométrico de las revistas cientı́ficas,

Indices of upper airway obstruction in patients with simultaneous chronic airflow limitation

In patients with chronic airflow limitation (CAL), the detection of upper airway obstruction (UAO) by analysis of forced flows can be difficult due to the masking of conventional UAO indices. We analyzed five indices: maximum inspiratory flow at 50% of forced vital capacity (FIF50), the ratio of maximum expiratory to inspiratory flow at 50% of forced vital capacity (FEF50/FIF50), the ratio FEV1/PEFR, the ratio FEV1 to forced expiratory volume in 0.5 s (FEV1/FEV0.5), and the ratio maximum voluntary ventilation (MVV)/FEV1, to determine their usefulness in evaluating patients with simultaneous UAO and CAL. One hundred and thirty-seven patients participated: 54 had UAO alone, 23 presented simultaneous UAO and CAL and 60 suffered from CAL with no evidence of UAO. The patients with UAO and CAL on the average presented fewer abnormal indices and these were less severely altered. Twenty-seven of the 60 with CAL alone presented at least one abnormal index, but in no case were more than two present. FEF50/FIF50 and FEV1/PEFR were significantly less sensitive in patients with both UAO and CAL than in those with UAO alone (35 vs. 85% and 52 vs. 72%, respectively). In all patients the most specific indices (100%) were FEF50/FIF50 and MVV/FEV1. The index MVV/FEV1 was the most accurate in patients with UAO and CAL. We conclude that when patients with CAL present 3 or more abnormal UAO indices, or have FEF50/FIF50 > or = 1 or MVV/FEV1 < or = 25, the possibility of simultaneous UAO must be strongly considered.

Analysis of microbiota in stable patients with chronic obstructive pulmonary disease

To identify the bacterial diversity (microbiota) in expectorated sputum, a pyrosequencing method that investigates complex microbial communities of expectorated sputum was done in 19 stable chronic obstructive pulmonary disease patients (mean (SD) FEV1: 47 (18%) of predicted value). Using conventional culture, 3 phyla and 20 bacterial genera were identified, whereas the pyrosequencing approach detected 9 phyla and 43 genera (p < 0.001). In sputum the prevalent genera with pyrosequencing approach were Streptococcus, Actinomyces, Neisseria, Haemophilus, Rothia, Fusobacterium, Gemella, Granulicatella, Porphyromonas, Prevotella and Veillonella. Enterobacteriaceae, detected frequently in conventional culture, were not significantly detected with pyrosequencing methods. In addition, we found that important pathogens such as Haemophilus and Moraxella were detected more frequently with the new genetic procedures. The presence of Enterobacteriaceae is probably overestimated with conventional culture, whereas other difficult cultivable pathogens are underestimated. These studies open a new perspective for evaluating the role of bacterial colonization in chronic obstructive pulmonary disease pathogenesis and progression.

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.

Interaction between linezolid and Mycobacterium tuberculosis in an experimental in vitro model

Cremades R, Rodríguez JC, Garcia‐Pachón E, Galiana A, Ruiz‐García M, López P, Royo G. Interaction between linezolid and Mycobacterium tuberculosis in an experimental in vitro model. APMIS 2011; 119: 304–8.

Urinothorax: an unexpected cause of severe dyspnea

Dear Editor: Recently, Tortora et al. [1] reported on a case of urinothorax with severe dyspnea. This description is of interest because urinothorax is rarely recognized. To date, less than 60 cases have been reported [2, 3]. However, to diagnose urinothorax is very important; in a patient with obstructive uropathy and pleural effusion, if the effusion is a urinothorax, no further diagnostic tests are necessary because it disappears after the resolution of the obstruction. To consider this possible diagnosis is of interest especially in patients whose obstruction is caused by a malignant disease. Due to this importance, we consider it to be of interest to present some clinical, radiological, and biochemical data that could help in its diagnosis. Reviewing the literature, we have found two groups of urinothorax: those associated with bilateral obstruction (prostate disease or bladder cancer, for instance) and those associated with a traumatic cause (including surgical injury or blunt trauma) [3]. In most cases, urinothorax do not produce respiratory symptoms, but cases with severe dyspnea have been described [1, 2]. In cases of unilateral lesion, the effusion tends to be ipsilateral to this side. Urinothorax resolves without treatment after the resolution of a urinary problem. Therefore, establishing the diagnosis is necessary to perform a thoracocentesis. The fluid looks and smells like urine and it is a transudate with a creatinine concentration higher in pleural fluid than in serum, as in the case reported by Tortora et al. [1]. Probably, urinothorax is more frequent than is recognized, but the scarcity of reported cases might be due to the low index of suspicion (it would not always be suspected) and because it occurs in a clinical scenario where urological problem predominates and rapidly resolves. The publication by Tortora et al. [1] demonstrates the contribution of emergency radiologists in the suspicion and the detection of this rare entity.

A simple C-reactive protein measurement for the differentiation between tuberculous and malignant pleural effusion: comment.

Chierakul and colleagues recently described that C-reactive protein (CRP) is a useful test in discriminating between tuberculous pleuritis (TBP) and malignant pleural effusion (MPE). Pleural fluid CRP values of ≥ 30 mg/L had a sensitivity of 72% with 93% specificity for diagnosing tuberculosis. They studied 115 patients with lymphocytic exudative pleural effusion due to tuberculosis or malignancy, but the authors excluded 33 patients with lymphocytic ‘nonspecific’ pleuritis. However, in our opinion, excluding this group of patients makes the cut-off values of the test difficult to apply in clinical practice. Chierakul et al. probably did not know our published experience in the measurement of CRP levels in pleural fluid. We consider that it could be of interest to comment here that our results, in some way, complete those reported by Chierakul et al. In a series of 123 consecutive patients with exudative pleural effusion (60 associated with malignancy and 63 benign effusions), we found that a pleural fluid CRP level below 20 mg/L suggested a malignant origin, and a level above 45 mg/L virtually ruled out this possibility. In another study that included 118 patients with lymphocytic pleural effusion (16 with TBP, 61 MPE, and 41 of other origin), we found that with values of pleural fluid CRP ≥ 30 mg/L for diagnosing TBP, sensitivity was 100% and specificity 71%, and for CRP ≥ 50 mg/L, sensitivity was 44% and specificity 96%. The differences in sensitivity, specificity and cut-off values are obviously due to the different composition of the patient groups in each study, however, the findings consistently indicate the usefulness of the CRP measurement in pleural fluid. In conclusion, we agree with Chierakul et al. that CRP measurement may be useful for the differentiation between TBP and MPE. The measurement of the CRP level is an inexpensive test and is easy to perform. A low pleural fluid level of CRP in exudative pleural effusions is highly indicative of malignancy, and in contrast, high levels of CRP in lymphocytic effusions are highly suggestive of TBP. Nevertheless, before interpreting cut-off values of CRP it is necessary to clearly know the groups in whom the test has been studied.

Flexible bronchoscopy in very old patients with lung cancer

Recently, Okachi et al. [1] published in the European Geriatric Medicine the results of flexible bronchoscopy in very old patients with lung cancer, and concluded that this technique leads to appropriate treatment decision in this group of patients. Our experience accords with that reported by Okachi et al. [1] in terms of safety and utility of bronchoscopy in octogenarians [2]; and we consider that we can contribute to this conclusion with additional information. In our series of octogenarian patients who underwent flexible bronchoscopy, lung cancer was eventually diagnosed in 35% of them [2]. 44% of these patients were treated with curative intent. Very interestingly, the one-year survival of these patients was of 33%, almost identical to the 1-year survival of lung cancer patients as a whole in our country (36%) [3]. In view of our findings and those reported by Okachi et al. [1], we can state that the age of the patients could not be considered a criterion for exclusion of further clinical tests in lung cancer suspicion. In view of the safety, diagnostic utility, and prognostic implications, very old patients deserve the adequate clinical evaluation, including bronchoscopy. Compliance with ethical standards