Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Inhaler Adherence in COPD: A Crucial Step Towards the Correct Treatment.

COPD is a typical example of chronic disease. As such, treatment adherence tends to be as low as between 30% and 50%, with specific issues in COPD due to the use of inhaled therapies. Decreased adherence in COPD is associated with worse outcomes, with increased risk for exacerbations and long-term mortality. Factors that impact adherence are multiple, some related to patient, some related to clinicians and finally some related to healthcare system. Among clinician factors, prescription of simplified treatment regimens delivered by an inhaler adapted to the patient's characteristics is crucial. Although it has been observed a huge improvement in the design and usability of inhaler devices for COPD in the last two centuries, there is still a clear gap in this field. Smart inhalers as well as simplified treatment regimens could improve adherence and therefore improve long-term outcomes in COPD.

ANTES: Un año después en la EPOC / ANTES Program: One Year on

No disponible

[Translated article] ANTES Program: One Year on / ANTES: Un año después en la EPOC

No disponible

Characterization of COPD Admissions During the First COVID-19 Outbreak.

Purpose: Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak. We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19. Patients and Methods: We conducted a case-control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020. Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated. Baseline and episode-related clinical characteristics were analyzed. Logistic regression analysis was performed to evaluate the risk for mortality. Results: During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19. A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19. COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p<0.001) and had higher mortality (44.9% vs 13.6% respectively, p<0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit. COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population. Inhaled corticosteroid use was not associated to mortality. Conclusion: Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis.

Microspirometers in the follow-up of COPD: advantages and disadvantages / El uso de los microespirómetros en el seguimiento de la EPOC: ventajas e inconvenientes

No disponible

Efficacy of FF/UMEC/VI compared with FF/VI and UMEC/VI in patients with COPD: subgroup analysis of the Spain cohort in IMPACT.

OBJECTIVES: The IMPACT trial has compared the benefit in the reduction of moderate/severe exacerbations of single inhaler triple therapy (SITT) with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus dual therapy with FF/VI (ICS/LABA) and UMEC/VI (LAMA/LABA) in the treatment of patients with chronic obstructive disease (COPD). This study performs a subgroup analysis of the cohort from Spain in the IMPACT study. MATERIALS AND METHODS: In IMPACT, a 52-week randomized, double-blind, parallel-group, multicenter study (N = 10,355), patients ⩾40 years of age with COPD and ⩾1 moderate/severe exacerbations in the previous year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg or UMEC/VI 62.5/25 µg administered via the Ellipta inhaler. Here, we present a subgroup analysis of the 499 patients from Spain, included in the intent-to-treat (ITT) population in the study. Endpoint assessed included exposure-adjusted rate of moderate and severe exacerbations. RESULTS: In the Spain cohort, the exposure-adjusted rate of on-treatment moderate/severe COPD exacerbations per year for FF/UMEC/VI was 1.31 versus 1.43 and 1.57 for FF/VI and UMEC/VI, respectively. No new adverse events were identified. The results are consistent with those observed in the overall ITT study population. CONCLUSION: In the Spain cohort of the IMPACT study, patients receiving triple therapy with FF/UMEC/VI had a lower exposure-adjusted rate of exacerbations compared with FF/VI and UMEC/VI, similar to the overall population.Study Title: A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary DiseaseURL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=CTT116855/ https://clinicaltrials.gov/ct2/show/NCT02164513Registration number: GSK (CTT116855/NCT02164513).The reviews of this paper are available via the supplemental material section.

The lung function profile of once-daily tiotropium and olodaterol via Respimat(®) is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler(®) (ENERGITO(®) study).

BACKGROUND: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting ß2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens. OBJECTIVE: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD. METHODS: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat(®) and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler(®) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks. RESULTS: Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24). CONCLUSION: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.

Comorbidity in chronic obstructive pulmonary disease. Related to disease severity?

BACKGROUND AND OBJECTIVE: Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. PATIENTS AND METHODS: In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. RESULTS: Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. CONCLUSION: COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity.

Prevalencia de anemia asociada a la enfermedad pulmonar obstructiva crónica. Estudio de las variables asociadas / Prevalence of Anaemia Associated With Chronic Obstructive Pulmonary Disease. Study of Associated Variables

Introducción: La anemia es una de las manifestaciones extrapulmonares de la enfermedad pulmonar obstructiva crónica (EPOC). Su prevalencia, su fisiopatología y su repercusión clínica son desconocidas. Los objetivos de nuestro estudio son determinar la prevalencia de la anemia en pacientes con EPOC en fase estable no atribuible a otras causas y establecer la relación de la anemia con variables clínicas, pronósticas y marcadores inflamatorios con un papel relevante en la EPOC. Métodos: Se incluyeron pacientes con EPOC en fase estable sin otras causas conocidas de anemia. Se realizaron pruebas de función respiratoria, determinación de eritropoyetina y marcadores inflamatorios séricos: PCR ultrasensible (PCR), fibrinógeno, interleucina 6 (IL-6), interleucina 8 (IL-8) y factor de necrosis tumoral alfa (TNF-α). Se registró el índice de masa corporal (IMC), el índice de Charlson y el BODE, el número de exacerbaciones en el año previo, la escala de disnea y la calidad de vida. Resultados: Se incluyeron 130 pacientes. La prevalencia de anemia fue del 6,2%. El valor de hemoglobina en los pacientes con anemia fue de 11,9 ± 0,95 g/dl. Los pacientes con anemia tenían un IMC más bajo (p = 0,03), un índice de Charlson mayor (p = 0,002), niveles de eritropoyetina más elevados (p = 0,016), una tendencia a presentar niveles más bajos de FEV1% (p = 0,08) y valores significativamente más bajos de IL-6 (p = 0,003) cuando se comparan con los pacientes no anémicos. Conclusiones: En nuestra serie, la anemia asociada a la EPOC es menos prevalente de lo publicado hasta la actualidad y guarda relación con determinados factores clínicos y marcadores inflamatorios (AU)

Background: Anaemia is one of the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). Its real prevalence, physiopathology and clinical repercussion are unknown. The objectives of our study were: to determine the prevalence of anaemia in patients with stable COPD not attributable to other causes and to establish the relationship of anaemia with clinical, prognostic and inflammatory markers with an important role in COPD. Methods: The study included stable COPD patients with no other known causes of anaemia. The following tests were carried out: respiratory function tests; serum determination of erythropoietin and inflammatory markers: high sensitivity C -reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor α (TNF-α). Body mass index (BMI), Charlson and BODE indices, the number of exacerbations in the previous year, dyspnoea and quality of life were also calculated. Results: One hundred and thirty patients were included. Anaemia prevalence was 6.2%. Mean haemoglobin value in anaemic patients was 11.9 ± 0.95 g/dL. Patients with anaemia had a lower BMI (P=0.03), higher Charlson index (P=0.002), more elevated erythropoietin levels (P=.016), a tendency to present a lower FEV1% value (P=.08) and significantly lower IL-6 values when compared to non-anaemic patients (P=0.003). Conclusions: In our series, the anaemia associated with COPD was less prevalent than that published in the literature to date, and was related to certain clinical and inflammatory markers (AU)

Prevalence of anaemia associated with chronic obstructive pulmonary disease. Study of associated variables.

BACKGROUND: Anaemia is one of the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). Its real prevalence, physiopathology and clinical repercussion are unknown. The objectives of our study were: to determine the prevalence of anaemia in patients with stable COPD not attributable to other causes and to establish the relationship of anaemia with clinical, prognostic and inflammatory markers with an important role in COPD. METHODS: The study included stable COPD patients with no other known causes of anaemia. The following tests were carried out: respiratory function tests; serum determination of erythropoietin and inflammatory markers: high sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor α (TNF-α). Body mass index (BMI), Charlson and BODE indices, the number of exacerbations in the previous year, dyspnoea and quality of life were also calculated. RESULTS: One hundred and thirty patients were included. Anaemia prevalence was 6.2%. Mean haemoglobin value in anaemic patients was 11.9±0.95g/dL. Patients with anaemia had a lower BMI (P=.03), higher Charlson index (P=.002), more elevated erythropoietin levels (P=.016), a tendency to present a lower FEV1% value (P=.08) and significantly lower IL-6 values when compared to non-anaemic patients (P=.003). CONCLUSIONS: In our series, the anaemia associated with COPD was less prevalent than that published in the literature to date, and was related to certain clinical and inflammatory markers.

Pronóstico tras una agudización grave de la EPOC tratada con ventilación mecánica no invasiva / Prognosis Following Acute Exacerbation of COPD Treated With Non-invasive Mechanical Ventilation

IntroducciónLos pacientes con EPOC que sobreviven a una exacerbación grave que necesita ventilación mecánica no invasiva son un grupo de mal pronóstico.ObjetivoConocer las tasas de reingreso y mortalidad durante el año siguiente a su alta y analizar los factores asociados a ambos desenlaces.MétodosUna cohorte de 93 pacientes con EPOC, que sobrevivieron a una exacerbación de la EPOC que precisó ventilación mecánica no invasiva, fue seguida tras el alta. Se midieron la necesidad de hospitalización por motivos respiratorios y la supervivencia, y se analizaron frente a posibles factores asociados a esos eventos mediante una regresión multivariante de riesgos proporcionales de Cox.ResultadosDurante el año siguiente al alta, 61 pacientes (66%) precisaron una nueva hospitalización. En el análisis multivariante, un valor bajo de FEV1 y una elevada estancia media durante la hospitalización se asociaron de forma independiente con un elevado riesgo de reingreso hospitalario. La probabilidad de supervivencia al año fue de 0,695 (IC95%: 0,589–0,778). En el análisis multivariante la edad, la PaCO2 antes de iniciar la ventilación mecánica no invasiva y los días de hospitalización en el año previo se asociaron de forma independiente con un elevado riesgo de mortalidad.ConclusionesEste grupo de pacientes con EPOC presenta una alta mortalidad y necesidad de rehospitalización en el año siguiente al alta. Las variables estudiadas relacionadas con la gravedad de la enfermedad de base y de la propia agudización demostraron estar asociadas a esos eventos y podrían utilizarse para la aplicación en este subgrupo de pacientes de programas específicos de seguimiento(AU)

IntroductionPatients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis.ObjectiveTo identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV.MethodsA cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis.ResultsOver the year following discharge, 61 patients (66%) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV1 value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO2 prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk.ConclusionsThis group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs(AU)

[Prognosis following acute exacerbation of COPD treated with non-invasive mechanical ventilation]. / Pronóstico tras una agudización grave de la EPOC tratada con ventilación mecánica no invasiva.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis. OBJECTIVE: To identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV. METHODS: A cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis. RESULTS: Over the year following discharge, 61 patients (66%) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV(1) value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO(2) prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk. CONCLUSIONS: This group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs.

Analysis of the molecular expression profile of non small cell lung carcinoma associated to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor to develop lung cancer but there are no different functional clusters of biomarkers between patients with non-small cell lung cancer (NSCLC) with or without COPD. To analyse protein expression, in order to find out whether samples of resected NSCLC from patients with COPD present a different molecular expression. Observational, cohort, concurrent study with sampling since treatment of disease in patients with NSCLC in initial stages (pIA-pIIB) treated surgically in our hospital between October 1993 and September 1997. The study consisted of the elaboration of tissue arrays with samples from resected tumor, using immunohistochemistry as a study method. Univariate analysis and logistic regression analysis were performed in order to determine molecular markers that showed a differential expression in NSCLC of the patients with COPD. We studied thirty-two proteins in 146 patients. 30% of the patients had COPD. Univariate analysis in patients with COPD showed one molecular marker to be overexpressed and five molecular markers to be underexpressed. Multivariate analysis in patients with COPD identified membranous beta-Catenin as a differential biomarker, which displayed an underexpression, with an Odds Ratio (95% Confidence Interval) of 0.26 (0.07-1.01). A significant lowest expression of membranous beta-catenin was detected in NSCLC of the patients with COPD.

[Failure of levofloxacin therapy in two cases of community-acquired pneumonia caused by fluoroquinolone-resistant Streptococcus pneumoniae and complicated with empyema]. / Fracaso terapéutico de levofloxacino en dos casos de neumonía adquirida en la comunidad complicada con empiema causados por Streptococcus pneumoniae resistente a fluoroquinolonas.

BACKGROUND: Community acquired pneumonia (CAP) due to Streptococcus pneumoniae is a frequent cause of morbidity and mortality. We communicate two cases of CAP with complications. In both cases levofloxacin-resistant S. pneumoniae was isolated in pleural effusion. Patient 1: A 51-year-old man who had not received previous treatment with quinolones was admitted to the hospital for CAP and initially treated with levofloxacin (500 mg/24h iv). Four days later pleural effusion developed and fluid culture isolated levofloxacin-resistant S. pneumoniae (MIC > 32 .g/ml). The outcome was favorable following chest tube placement and treatment with beta-lactam antibiotics. Patient 2: A 73-year-old man with a history of chronic obstructive pulmonary disease was admitted due to CAP and was initially treated with levofloxacin (500 mg/24 h iv). He was transferred to our hospital after 10 days of treatment with this antibiotic, following the development of pleural effusion with isolation of levofloxacin-resistant S. pneumoniae (MIC = 12 .g/ml). The patient was treated with chest tube placement and beta-lactam antibiotics with a favorable outcome. CONCLUSIONS: Patients with CAP treated empirically must be closely followed, both clinically and radiologically, to facilitate early detection of complications due to bacterial resistance to the prescribed antibiotic. Patients with CAP who have received quinolones in the weeks before the development of pneumonia should not been treated empirically with these antibiotics because of the risk of resistance development.

Fracaso terapéutico de levofloxacino en dos casos de neumonía adquirida en la comunidad complicada con empiema causados por Streptococcus pneumoniae resistente a fluoroquinolonas / Failure of levofloxacin therapy in two cases of community-acquired pneumonia caused by fluoroquinolone-resistant Streptococcus pneumoniae and complicated with empyema

Antecedentes. La neumonía adquirida en la comunidad (NAC) por Streptococcus pneumoniae es una causa frecuente de mortalidad y morbilidad. Se describen 2 casos de NAC tratadas con levofloxacino que se complicaron. En ambos casos se aisló en líquido pleural S. pneumoniae resistente al antibiótico empleado. El primer caso correspondía a un varón de 51 años, no tratado previamente con quinolonas. Ingresó en el hospital por NAC tratada inicialmente con levofloxacino (500 mg/24 h i.v.). A los 4 días aparece un derrame pleural en el que se aísla S. pneumoniae resistente a levofloxacino (concentración inhibitoria mínima [CIM] > 32 µg/ml). El paciente evolucionó favorablemente mediante drenaje del derrame y tratamiento con antibiótico betalactámico. El segundo caso era un varón de 73 años con antecedentes de enfermedad pulmonar obstructiva crónica. Ingresa por NAC tratada inicialmente con levofloxacino (500 mg/24 h i.v.). Fue remitido a nuestro hospital por presencia de derrame pleural en el que creció S. pneumoniae resistente a levofloxacino (CIM = 12 µg/ml) tras 10 días de tratamiento antibiótico. El paciente evolucionó de manera favorable mediante drenaje del derrame y tratamiento con antibiótico betalactámico. Conclusiones. Los pacientes con NAC en los que se inicia tratamiento antibiótico empírico deben vigilarse estrechamente desde el punto de vista clínico y radiológico, para la detección precoz de complicaciones por resistencia bacteriana al antibiótico empleado. En los pacientes con NAC que hayan recibido quinolonas en las semanas previas al desarrollo de la neumonía no es recomendable iniciar tratamiento empírico con estos antibióticos dado el riesgo de desarrollo de resistencias (AU)

Background. Community acquired pneumonia (CAP) due to Streptococcus pneumoniae is a frequent cause of morbidity and mortality. We communicate two cases of CAP with complications. In both cases levofloxacin-resistant S. pneumoniae was isolated in pleural effusion. Patient 1: A 51-year-old man who had not received previous treatment with quinolones was admitted to the hospital for CAP and initially treated with levofloxacin (500 mg/24h iv). Four days later pleural effusion developed and fluid culture isolated levofloxacin-resistant S. pneumoniae (MIC > 32 µg/ml). The outcome was favorable following chest tube placement and treatment with beta-lactam antibiotics. Patient 2: A 73-year-old man with a history of chronic obstructive pulmonary disease was admitted due to CAP and was initially treated with levofloxacin (500 mg/24 h iv). He was transferred to our hospital after 10 days of treatment with this antibiotic, following the development of pleural effusion with isolation of levofloxacin-resistant S. pneumoniae (MIC = 12 µg/ml). The patient was treated with chest tube placement and beta-lactam antibiotics with a favorable outcome. Conclusions. Patients with CAP treated empirically must be closely followed, both clinically and radiologically, to facilitate early detection of complications due to bacterial resistance to the prescribed antibiotic. Patients with CAP who have received quinolones in the weeks before the development of pneumonia should not been treated empirically with these antibiotics because of the risk of resistance development (AU)

Clinical implications of appearance of pleural fluid at thoracentesis.

STUDY OBJECTIVES: The aims of this study were to describe the different appearances of pleural fluid during thoracentesis and their frequency in relation to diagnosis, and to evaluate the causes and clinical implications of bloody pleural effusions. SETTING: Tertiary care, university-affiliated hospital. SUBJECTS AND METHODS: Seven hundred fifteen patients with pleural effusion were prospectively assessed from December 1991 to December 1997. INTERVENTIONS: The appearance of the fluid was assessed in a glass assay tube containing 10 mL of pleural fluid. RESULTS: The most common presentations were serous and blood tinged, with 80% of the fluids fitting into one of these categories. The most frequent cause of watery fluid was transudate, although most transudates were classified as serous effusions. There were 59 bloody and 656 nonbloody pleural fluids. The most common cause of bloody pleural effusion (BPE) was malignancy (47%). Fluid with a bloody appearance slightly increased the probability of malignancy in our series (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01 to 2.94; p = 0.04). Nevertheless, only 11% of the neoplastic effusions were BPE. Other common causes of BPE were posttraumatic (12%) or parapneumonic (10%) pleural effusions. Tuberculosis and transudates were uncommon causes of BPE. Fluid that was bloody in appearance decreased the probability for both diseases (OR, 0.15; 95% CI, 0.04 to 0.57; p = 0.003 and OR, 0.25; 95% CI, 0.06 to 0.95; p = 0.04, respectively). CONCLUSIONS: Serous and blood tinged were the most common presentations of pleural fluid at thoracentesis. Almost half of BPEs were secondary to neoplasms, but only 11% of the neoplastic effusions were BPEs. Other common causes of BPE were parapneumonic and posttraumatic.

Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis.

PURPOSE: To assess the utility of interferon gamma levels, including identification of the best cutoff for the diagnosis of tuberculosis. METHODS: We prospectively studied consecutive patients in a tertiary care, university-affiliated hospital who had pleural effusions. Interferon gamma levels were measured blindly by radioimmunoassay. The diagnosis of tuberculosis was established using prespecified standard criteria. RESULTS: Of the 595 patients with pleural effusions, 82 patients (14%) had tuberculosis. The area under the receiver operating characteristic (ROC) curve for elevated interferon gamma levels in the diagnosis of tuberculosis was 0.99 (95% confidence interval [CI]: 0.97 to 1.00). A cutoff of 3.7 IU/mL yielded a sensitivity of 0.98 (95% CI: 0.91 to 1.00) and a specificity of 0.98 (95% CI: 0.96 to 0.99). The areas under the ROC curves, and the test's sensitivity and specificity, were similar among patients of different ages and by percentage of lymphocytes in the pleural fluid. In 5 of the 28 patients with hematologic malignancies, interferon gamma levels were slightly above the cutoff; no patient with vasculitis or granulomatous diseases had levels higher than 3.7 IU/mL. The 14 immunocompromised patients and the 3 transplantation patients with tuberculosis had interferon gamma levels greater than the cutoff. CONCLUSION: Elevated pleural interferon gamma levels (>3.7 IU/mL) are very valuable in diagnosing pleural tuberculosis. Patients with pleural effusion due to hematologic neoplasms occasionally have levels slightly above the cutoff.