Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results.

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate.

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.

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.

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.

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.

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.

Amylase levels in pleural effusions: a consecutive unselected series of 841 patients.

STUDY OBJECTIVES: To describe the causes and relative frequency of amylase-rich pleural effusion (ARPE), and to study the origin and histologic type of the tumors with ARPE, the strength of the association between ARPE and the result of pleural cytology, and whether pleural amylase (PA) is a prognostic factor in the survival of patients with a malignant pleural effusion. SETTING: Tertiary-care, university-affiliated hospital. PATIENTS: Eight hundred forty-one consecutive patients with pleural effusion prospectively assessed from 1991 to 1999. RESULTS: There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis, pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six percent of patients in our series and 61% of patients with ARPE had a neoplastic disease (odds ratio [OR], 3; p < 0.001); this association got much stronger for cases with PA levels > or = 600 IU/L (95th percentile); [OR, 10; p < 0.001]. The most frequent tumor origin was lung cancer (13 cases). Adenocarcinoma was the most frequent histologic type (18 cases). Two mesothelioma effusions were ARPEs. There was a positive association between ARPE and the finding of tumor cells in pleural fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels > or = 600 IU/L identified a group of patients with quite a short median survival (p = 0.016). CONCLUSIONS: The most common cause of ARPE was neoplasm. There was a positive association between ARPE and malignancy, stronger with the highest levels (95th percentile). Lung cancer and adenocarcinoma were the most common tumor and histologic type associated with ARPE. Mesothelioma may also produce ARPE. There was an association between ARPE and the finding of tumor cells in the pleural fluid. The highest PA levels identified a group of patients with a median shorter survival.

Endobronchial hamartoma.

OBJECTIVES: To describe clinical, endoscopic, radiographic, and follow-up characteristics of a series of patients in whom endobronchial hamartoma (EH) had been diagnosed. METHODS: Retrospective study of all cases of hamartoma diagnosed by bronchial biopsy between 1974 and 1997 in a tertiary referral hospital in Madrid, Spain. RESULTS: EH was diagnosed 47 patients during the study period. Four patients were excluded from the study because no clinical history was available. We analyzed the cases of 43 patients (37 men and 6 women), with a mean (+/- SD) age of 62 +/- 12 years. Seven patients had a concurrent lung neoplasm, and the EH was an incidental endoscopic finding. Among the other 36 patients, 31 had a new onset of respiratory symptoms, most commonly, recurrent respiratory infections in 16 patients (44%) and hemoptysis in a further 12 patients (33.4%). Chest radiograph findings were abnormal in 38 of 43 patients. At bronchoscopy, the lesions were equally distributed throughout the right and left lungs with no clear lobar predilection. Endobronchial obstruction was evident in 26 patients (72.2%) without concurrent neoplasm, 17 of whom underwent resection with a rigid bronchoscope and laser, with total resolution in 13 patients. Partial resolution was achieved in four patients, two of whom needed a second endoscopic procedure. Five patients were treated with open lung surgery. Clinical and endoscopic follow-up was performed in 23 patients at 1 to 73 months (mean, 17 months), and recurrence was found in 4 patients. CONCLUSION: EH frequently produces respiratory complaints and radiographic abnormalities. Patients with endobronchial obstructions had satisfactory responses to endoscopic therapy.

Diagnostic value of CA 549 in pleural fluid. Comparison with CEA, CA 15.3 and CA 72.4.

Several tumor markers have been evaluated in pleural fluid, but their clinical role has not been firmly established. The aim of this study is to determine the diagnostic value of carbohydrate antigen 549 (CA 549) levels in pleural fluid, and to compare it with another previously studied tumor markers: carcinoembryonic antigen (CEA), CA 15.3 and CA 72.4. We prospectively studied 252 patients with pleural effusion: 101 malignant (20 mesothelioma) and 151 of several benign diseases. The levels of the tumor markers were measured by immunoradiometric assays (RIA). CA 549 in pleural fluid has an acceptable sensitivity (0.49), with high specificity (0.99). The best combination of tumor markers for differentiating malignant from benign effusions was CA 549+CEA+CA 15.3, with a sensitivity of 0.65, specificity of 0.99 and accuracy of 0.85. The addition of any one tumor marker assay consistently improved the diagnostic value of cytology. In our study, none of the tumor markers was organ-specific. When mesothelioma and hematological malignancy were ruled-out, the combination of CA 549+CEA+CA 15.3, improved the results up to a sensitivity of 0.77, specificity of 1 and accuracy of 0.92. In conclusion, CA 549 assay has an acceptable sensitivity with high specificity. The best combination of tumor markers in this series with a high relative frequency of mesothelioma and low frequency of breast carcinoma was CA 549+CEA+CA 15.3. Individual tumor markers or their combination increased the sensitivity of pleural cytology.

Persistent cavitations in pulmonary mucormycosis after apparently successful amphotericin B.

A 67-year-old diabetic male developed bilateral pulmonary mucormycosis (PM). After long-term treatment with amphotericin B (cumulative dose of 30.6 g), clinical resolution was obtained, but small radiographic cavitations persisted. A late relapse occurred and bilateral lobectomy led to a definitive cure. Amphotericin B is not able to penetrate properly into PM cavitations. We suggest that persistence of cavitations should lead to consideration of surgery, even after a good response to amphotericin B.

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.

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.

[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.