Background: Pneumonia is a common disease with a high mortality rate, being the sixth leading cause of death among elderly people in the USA and the fifth among those in Brazil. Initial treatment of pneumonia is usually empirical since the ethiological agent is identified in only approximately 50% of cases. Therefore, several scientific societies have defined some guidelines for initial antimicrobial therapies. Objectives: This study evaluated adherence to the guidelines set forth by the Consenso Brasileiro sobre Pneumonias (Brazilian Consensus on Pneumonia) for treatment of community-acquired pneumonia in hospitalized elderly patients. Method: Fifty-four patients, aged 60 or over, hospitalized at Londrina University Hospital with community-acquired pneumonia between 2 August 1999 and 2 August 2000 were evaluated. Whether their treatment adhered or did not adhere to guidelines, the patients were compared in terms of 30-day mortality, average time for clinical stabilization, average length of hospital stay, cost of treatment and severity score. Results: The average age was 74.1, and 61.1% of the patients were treated in accordance with the Brazilian guidelines for treatment of community-acquired pneumonia. There were no differences in length of hospital stays, cost of treatment, time to clinical stability and severity score between the two groups (adherent and non-adherent). However, there was a difference in mortality. The rate of mortality was higher in patients with pneumonia severity index (PSI) scores of IV or V who were treated according to the guidelines than in those with the same score whose treatment was non-adherent (p = 0.04). In general, PSI score was related to mortality. The mortality rate among patients with scores of II and III was 9.5%, compared with 30.3% in patients with scores of IV and V. Conclusion: Adherence to the Brazilian guidelines for treatment of community-acquired pneumonia in elderly patients was satisfactory, and there was no difference in results between both groups, except for the higher mortality rate found for patients with higher PSI scores who were treated according to the guidelines. A positive correlation was found between PSI score and mortality.

Keywords: Pneumonia. Health Planning Guidelines. Community-Acquired Infections. Health Services for the Aged.

Objective: To evaluate the agreement between the criteria used for hospitalization of patients with community-acquired pneumonia (CAP) and those of the Brazilian Thoracic Association guidelines, and to evaluate the association of that agreement with 30-day mortality. Secondarily, to evaluate the agreement between the treatment given and that recommended in the guidelines with length of hospital stay, microbiological profile, 12-month mortality, complications, ICU admission, mechanical ventilation, and 30-day mortality. Methods: This was a retrospective study involving adult patients hospitalized between 2005 and 2007 at the Federal University of Minas Gerais Hospital das Clínicas, located in Belo Horizonte, Brazil. Medical charts and chest X-rays were reviewed. Results: Among the 112 patients included in the study, admission and treatment criteria were in accordance with the guidelines in 82 (73.2%) and 66 (58.9%), respectively. The 30-day and 12-month mortality rates were 12.3% and 19.4%, respectively. The 30-day mortality rate was lower for patients in whom the CRB-65 (mental Confusion, Respiratory rate, Blood pressure, and age ≥ 65 years) score was 1-2 and the antibiotic therapy was in accordance with the guidelines (p = 0.01). Cerebrovascular disease and appropriate antibiotic therapy showed independent associations with 30-day mortality. There was a trend toward an association between guideline-concordant antibiotic therapy and shorter hospital stay. Conclusions: In the population studied, admission and treatment criteria that were in accordance with the guidelines were associated with favorable outcomes in hospitalized patients with CAP. Cerebrovascular disease, as a risk factor, and guideline-concordant antibiotic therapy, as a protective factor, were associated with 30-day mortality.

Keywords: Pneumonia/therapy; Pneumonia/mortality; Hospitalization; Guideline adherence.

Community-acquired pneumonia continues to be the acute infectious disease that has the greatest medical and social impact regarding morbidity and treatment costs. Children and the elderly are more susceptible to severe complications, thereby justifying the fact that the prevention measures adopted have focused on these age brackets. Despite the advances in the knowledge of etiology and physiopathology, as well as the improvement in preliminary clinical and therapeutic methods, various questions merit further investigation. This is due to the clinical, social, demographical and structural diversity, which cannot be fully predicted. Consequently, guidelines are published in order to compile the most recent knowledge in a systematic way and to promote the rational use of that knowledge in medical practice. Therefore, guidelines are not a rigid set of rules that must be followed, but first and foremost a tool to be used in a critical way, bearing in mind the variability of biological and human responses within their individual and social contexts. This document represents the conclusion of a detailed discussion among the members of the Scientific Board and Respiratory Infection Committee of the Brazilian Thoracic Association. The objective of the work group was to present relevant topics in order to update the previous guidelines. We attempted to avoid the repetition of consensual concepts. The principal objective of creating this document was to present a compilation of the recent advances published in the literature and, consequently, to contribute to improving the quality of the medical care provided to immunocompetent adult patients with community-acquired pneumonia.

Keywords: Pneumonia; Diagnosis; Epidemiology; Practice guideline; Primary prevention.

Objectives: To evaluate the self-reported degree of adherence to treatment in patients with cystic fibrosis (CF), investigating associations with characteristics of the disease and with the degree of adherence perceived by health professionals. Methods: This was a prospective, cross-sectional study involving patients with CF monitored at a Program for Adults with CF. The degree of adherence was evaluated using a questionnaire. Patients were divided into two groups: greater degree of adherence and moderate/poor degree of adherence. Clinical data, Shwachman-Kulczycki clinical score, Brasfield radiographic score and spirometry data were obtained for all patients. Results: Out of 38 patients studied, 31 (81.6%) were classified as presenting a greater degree of adherence and 7 (18.4%) as presenting a moderate/poor degree of adherence. The self-reported patient adherence score correlated with the clinical score (r = −0.36, p = 0.028). The self-reported patient adherence score (median = 0.79) was higher than that perceived by health professionals (median = 0.71, p = 0.003). A greater degree of adherence was self-reported for respiratory therapy (by 84.2%), exercise (by 21.1%), prescribed diet (by 65.8%), pancreatic enzymes (by 96.3%), vitamins (by 79.4%), inhaled antibiotic therapy (by 76.7%) and inhaled DNase (by 79.4%). Conclusions: Self-reported adherence of patients attending a Program for Adults with CF was good. The self-reported patient adherence score correlated inversely with the clinical score. Self-reported patient adherence was greater than the adherence perceived by health professionals.

Keywords: Cystic fibrosis; Patient compliance; Therapeutics.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression) and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions.

Keywords: Cystic fibrosis/diagnosis; Cystic fibrosis/therapy; Cystic fibrosis/complications; Practice guideline.

Objective: To evaluate the association between adherence to treatment and mortality among Chronic Obstructive Pulmonary Disease (COPD) patients treated in the Brazilian public health system. Methods: This is cohort study of moderate-to-severe COPD patients monitored in a public pharmaceutical care-based Disease Management Program (DMP). All subjects who died one year after the beginning of the cohort were age-matched with those who remained alive at the end of the cohort period. Treatment adherence was measured through pharmacy records. Patients who received at least 90% of the prescribed doses were considered adherent to treatment. Results: Of the 333 patients (52.8% age = 65 years, 67.9% male), 67.3% were adherent to treatment (adherence rate, 87.2%). Mortality was associated with lack of adherence (p = 0.04), presence of symptoms (mMRC = 2) and COPD treatment use. The death was associated with non-adherence, presence of symptoms and previous hospitalization. After adjustment, non-adherent patients to treatment were almost twice times likely to die compared to those adherents (Hazard Ratio (HR) 1.86; CI 1.16-2.98, p = 0.01). Conclusion: Non-adherence to treatment was associated with higher mortality among moderate-to-severe COPD patients treated in the Brazilian public health system. Strategies to monitor and optimize adherence should be strengthened to reduce COPD-related mortality.

Keywords: COPD; Treatment adherence; Mortality; Pharmaceutical care.

Surgical resection is the primary treatment option for early-stage non-small cell lung cancer, lobectomy being considered the standard of care. In elderly patients, physiological characteristics can limit the suitability for surgery and the extent of resection. Sublobar resection (SLR) can be offered as an alternative. The aim of this real-world analysis was to compare lobectomy and SLR in terms of recurrence and survival rates in patients over 70 years of age.

Keywords: Carcinoma, non-small-cell lung/mortality; Carcinoma, non-small-cell lung/surgery; Recurrence; Aged; Aged, 80 and over.

Abstract Objective: To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma, to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response. Methods: Prospective cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia, Brazil. The study comprised 160 patients with severe asthma, monitored for 180 days in order to evaluate adherence (dependent variable) to the prescribed inhaled corticosteroid. Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a standardized questionnaire. Patients recorded the missed doses in a diary. Results: Of the 160 patients, 158 completed the study. Adherence rate was 83.8%. Of the 158 patients, 112 (70.9%) were considered adherent (cut-off point: 80% of prescribed doses administered). There was a significant association between asthma control and adherence to treatment. Predictors of poor adherence were adverse effects, living far from the referral center, limited resources to pay for transportation and dose schedule. Other factors, such as depressive symptoms, religion and economic status, were not associated with poor adherence. Conclusions: Adherence to asthma treatment was high and was associated with the clinical response to treatment, in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center.

Keywords: Asthma; Directly observed therapy; Treatment outcome; Patient compliance; Pharmacy.

Objective: To describe the demographic characteristics, everyday habits, socio-economic conditions, clinico-epidemiological profiles and access to health care services among the elderly patients with tuberculosis diagnosed and treated in the city of Recife, Brazil, comparing them to those observed in young adults with tuberculosis. Methods: A case-control type strategy was used to evaluate a cohort of patients with tuberculosis, all of whom were treated in public health care facilities in Recife between May of 2001 and July of 2003. Results: The final cohort consisted of 1127 patients: 136 elderly patients (cases) and 991 young adults (controls). In both groups, males predominated, and the most common form of tuberculosis was the pulmonary form. Alcoholism was more common in the control group, whereas illiteracy was more common in the case group. There were fewer complaints of cough, sweats and chest pain among the patients in the case group than among those in the control group. Serological testing for the human immunodeficiency virus was performed in only 29 patients (2.6%). The percentage of positive sputum smear microscopy results, as well as that of positive cultures, was higher in the controls. Prior to being diagnosed with the disease, patients in both groups had sought treatment at more than two health care facilities and had waited more than two months (after first seeking treatment). The elderly patients presented higher indices of cure and were more often compliant with the treatment regimen, yet presented higher mortality rates. Conclusion: In the population studied, the elderly presented less cough, fewer episodes of night sweats and less chest pain, as well as less often presenting positivity on complementary exams. Nevertheless, the mortality rate was higher among the elderly patients than among the young adult patients. Elderly patients with tuberculosis constitute a population that should be given special attention in public health care facilities.

Keywords: Tuberculosis; Elderly; Case-control; Brazil

Objective: To evaluate the management of asthma attacks in children up to five years of age treated in the pediatric emergency room of a hospital in the metropolitan area of the city of Recife, Brazil, as well as to determine whether the way in which asthma attacks are managed can influence the duration of emergency room visits for such children. Methods: A descriptive, exploratory study employing a quantitative, cross-sectional approach. The study sample comprised 246 children treated for asthma attacks in an emergency room. The approach used was evaluated in comparison with the approach recommended in the III Brazilian Consensus on Asthma Management, as was the length of time each child spent in the emergency room. Results: In 69 (28.1%) of the cases, the medications were used in accordance with the Consensus guidelines. In 34 (13.8%) of the cases, the doses used were those recommended in the Consensus guidelines, and the guidelines regarding nebulization procedures were followed in 33 cases (13.4%). No correlation was found between the approach taken and the length of the emergency room visit. In the logistic regression analysis, we observed that the adjusted risk of being released from the emergency room sooner than recommended in the Consensus guidelines (a length of time sufficient to allow the response to the treatment to be analyzed) was four times and fifteen times greater, respectively, for children with mild persistent asthma and for those with intermittent asthma. Conclusion: Although there are obstacles to using the asthma management approach recommended in the Consensus guidelines (such obstacles including the lack of familiarity with the guidelines on the part of the multidisciplinary team, as well as the lack of recommended material and therapeutic resources), the duration of emergency room visits was found to be related to the degree of asthma severity.

Keywords: Emergency medicine; Pediatrics; Asthma; Status asthmaticus

Objective: To implement community-acquired pneumonia (CAP) guidelines at a public hospital in Brazil and to evaluate the impact of these guidelines on health care quality. Methods: A quasi-experimental study, with a before-and-after design, involving adult patients diagnosed with CAP and hospitalized between July of 2007 and October of 2008 in the general ward of the Marília School of Medicine Hospital das Clínicas, located in the city of Marília, Brazil. Results: During the study period, 68 patients were diagnosed with CAP: 48 before the implementation of the guidelines and 20 after their implementation. After the implementation of the guidelines, 85% of the cases were treated in accordance with the guidelines, and there was a significant increase in the use of antibiotic therapy for atypical bacteria in patients with severe CAP (6.3% vs. 75.0%; p < 0.001). Comparing the pre-implementation and post-implementation periods, we observed a trend toward a decrease in the mortality (35.4% vs. 15.0%; p = 0.09) and toward an increase in the recording of SpO2 in the medical charts of the patients (18% vs. 30%; p = 0.42). During the study period, the degree of severity was not recorded on the medical charts of most patients. In addition, the initiation of antibiotic therapy followed a pre-established schedule, regardless of the severity of the infection. Conclusions: This study showed that, although the development and implementation of CAP guidelines promoted the optimization of the treatment, there were no significant differences regarding the assessment of severity, SpO2 recording, or the initiation of antibiotic therapy. Therefore, strategies that are more effective are needed in order to modify variables related to the work of physicians and nurses.

Keywords: Guideline adherence; Pneumonia; Health care quality, access, and evaluation; Community-acquired infections.

Com o objetivo de determinar a necessidade de confirmação microscópica do diagnóstico de pneumonia por Pneumocystis carinii (PPC), comparando grupos de pacientes tratados empiricamente com aqueles com confirmação diagnóstica, foram revisados os dados clínicos e laboratoriais de 82 pacientes internados em nossa instituição com infecção respiratória durante o ano de 1994. Estes pacientes formaram um grupo PPC (n = 37), dos quais 17 tiveram diagnóstico confirmado e 20 foram tratados empiricamente; e um grupo não-PPC (n = 45), com infecção respiratória que não PPC. O grupo PPC diferiu significativamente dos pacientes não-PPC por apresentarem maior duração dos sintomas, dispnéia mais freqüente, predomínio de lesões radiológicas bilaterais, menor contagem de células CD4 e menor uso de profilaxia anti-PPC. Quando comparamos os pacientes tratados empiricamente para PPC com os que tiveram confirmação diagnóstica de PPC, não observamos diferença estatisticamente significativa em qualquer das variáveis estudadas, exceto por um maior nível sérico de DHL nos pacientes com diagnóstico confirmado. Portanto, concluímos que confirmação microscópica pode não ser essencial em pacientes infectados pelo HIV com achados típicos de PPC e que tratamento empírico baseado no diagnóstico clínico pode ser uma alternativa razoável neste grupo de pacientes.

Keywords: PCP management. Empiric treatment.

Objective: To describe the clinical and therapeutic aspects of pulmonary tuberculosis and compare the adverse effects of the treatment and its outcome in elderly and nonelderly patients. Methods: This was a case-control study of 117 elderly individuals (over the age of 60 years) and 464 nonelderly individuals (aged 15-49 years). All subjects presented pulmonary tuberculosis that had been diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 1980 and 1996. Results: In the elderly group, pulmonary tuberculosis was found to be correlated with diabetes (OR = 3.98; 95% CI = 2.07-7.65; p = 0.001), lung disease (OR = 7.24; 95% CI = 3.64‑14.46; p = 0.001) and heart disease (OR = 5.86; 95% CI = 2.88-11.95; p = 0.001). Smoking (OR = 2.07; 95% CI = 1.26‑3.42; p = 0.002) and alcohol abuse (OR = 1.63; 95% CI = 1.01-2.68; p = 0.041) were also more common in the elderly group. In the elderly group, the treatment more frequently resulted in adverse reactions (OR = 1.62; 95% CI = 1.04-2.54; p = 0.024), especially gastrointestinal reactions (OR = 1.64; 95% CI = 1.01-2.77; p = 0.047), and treatment efficacy was lower: cure rate, 51%; mortality rate, 24%. Treatment adherence was low (approximately 77%) in both groups. Conclusions: In the elderly group, adverse reactions were more common, treatment outcomes were less favorable, there was a greater frequency of clinical complications and deaths related to drug toxicity, and the prevalence of concomitant diseases was higher.

Keywords: Tuberculosis, pulmonary; Aged; Drug therapy; Treatment outcome.

Lipoid pneumonia is a rare disease resulting from the micro-aspiration of lipid formulations. Making a diagnosis of lipoid pneumonia requires a high degree of clinical suspicion. Herein, we report the case of a female patient with a history of breast cancer, presenting progressive dyspnea and cough, together with radiological findings of bilateral pulmonary infiltrate. The working diagnosis of lymphangitic carcinomatosis, for which chemotherapy would be indicated, was called into question based on the high-resolution computed tomography findings and on the fact that the patient had a history of chronic ingestion of laxatives containing mineral oil. A lung biopsy confirmed a diagnosis of lipoid pneumonia, which should always be considered in patients with diffuse lung disease having been exposed to potential causative agents.

Keywords: Pneumonia, lipid; Tomography, X-Ray Computed; Mineral oil; Case Reports [Publication type]

Objective: To assess the incidence of necrotizing pneumonia (NP) in children submitted to thoracoscopy, comparing patients with and without NP in terms of the presentation and clinical evolution. Methods: A retrospective study of children with pleural empyema submitted to thoracoscopy. Thoracoscopy was performed in patients not previously submitted to thoracic drainage and in whom there was evidence of loculated effusion or pneumothorax, as well as in those previously submitted to thoracic drainage and in whom there was persistent pneumothorax or fever with purulent discharge. On the basis of the thoracoscopy findings, patients were distributed into two groups: those with NP (NP group) and those without (no-NP group). Results: The study sample comprised 52 patients. Of the 24 patients with NP, 19 (79%) had undergone thoracic drainage prior to thoracoscopy, 11 (46%) presented with pneumothorax, and 16 (67%) developed bronchopleural fistula. In the NP group, the median drainage time and the median length of hospital stay were 18 and 19 days, respectively. Of the 28 patients without NP, 10 (36%) had undergone thoracic drainage prior to thoracoscopy, 9 (32%) presented pneumothorax, and 5 (18%) developed bronchopleural fistula. In the no-NP group, the median drainage time and the median length of hospital stay were 6 and 10 days, respectively. Conclusions: Pneumothorax should raise the suspicion of NP. Early thoracoscopy can be a valuable treatment option for NP in children because it hastens recovery in comparison with the medical treatment alone and avoids extensive late thoracotomy lung resections.

Keywords: Keywords: Empyema, pleural; Thoracoscopy; Pneumonia; Child.

Objective: To determine, based on international guidelines for asthma management, the appropriateness of the treatment that the Unified Health Care System provides to patients with asthma. Methods: This was a cross-sectional study involving patients suspected of having asthma and referred to the Pulmonology Clinic of the Federal University of Minas Gerais Hospital das Clínicas, Brazil, between November of 2006 and October of 2007. Results: A total of 102 patients were included, and 70 were diagnosed with asthma. The previous treatment was consistent with the guidelines in 18.6% of the patients; 50.0% of the patients had previously been submitted to spirometry, and 34.3% had previously been submitted to PEF. The most frequently prescribed medication was short-acting β2 agonists (90.3%). Conclusions: The results show that the majority of non-specialized physicians working within the public health care system do not manage the treatment of patients with asthma in accordance with the guidelines. This situation calls for continuing medical education programs that prioritize primary care.

Keywords: Asthma; Guideline adherence; Therapeutics; Public health.

Objective: To determine the prevalence of ventilator-associated pneumonia in an intensive care unit, as well as to identify related factors and characterize patient evolution. Methods: This study evaluated 278 patients on mechanical ventilation for more than 24 hours in a university hospital. Results: Ventilator-associated pneumonia developed in 38.1% of the patients, translating to 35.7 cases/1000 ventilator-days: 45.3% were caused by gram-negative agents (Pseudomonas aeruginosa accounting for 22%); and multidrug resistant organisms were identified in 43.4%. In the ventilator-associated pneumonia group, time on mechanical ventilation, time to mechanical ventilation weaning, hospital stays and intensive care unit stays were all longer (p < 0.001). In addition, atelectasis, acute respiratory distress syndrome, pneumothorax, sinusitis, tracheobronchitis and infection with multidrug resistant organisms were more common in the ventilator-associated pneumonia group (p < 0.05). Mortality rates in the intensive care unit were comparable to those observed in the hospital infirmary. Associations between ventilator-associated pneumonia and various factors are expressed as odds ratios and 95% confidence intervals: acute sinusitis (38.8; 3.4-441); > 10 days on mechanical ventilation (7.7; 4.1-14.2); immunosuppression (4.3; 1.3-14.3); acute respiratory distress syndrome (3.5; 1.4-9.0); atelectasis (3.0; 1.2-7.3); cardiac arrest (0.18; 0.05-0.66); and upper gastrointestinal tract bleeding (0.07; 0.009-0.62). The variables found to be associated with in-hospital death were as follows: chronic renal failure (26.1; 1.9-350.7); previous intensive care unit admission (15.6; 1.6-152.0); simplified acute physiologic score II > 50 (11.9; 3.4-42.0); and age > 55 years (4.4; 1.6-12.3). Conclusion: Ventilator-associated pneumonia increased the time on mechanical ventilation and the number of complications, as well as the length of intensive care unit and hospital stays, but did not affect mortality rates.

Keywords: Bacterial pneumonia; Hospital infection; Intensive care units; Prognosis; Prospective studies; Intensive care medicine

Objective: To describe the results of the surgical treatment of children with necrotizing pneumonia. Methods: A retrospective analysis of the medical charts of 20 children diagnosed with necrotizing pneumonia and submitted to surgical treatment between March of 1997 and September of 2008 in the thoracic surgery departments of two hospitals in the city of Manaus, Brazil. We compiled data regarding age, gender, etiologic agent, indications for surgery, type of surgical resection performed, and postoperative complications. Results: The mean age of the patients was 30 months. Of the 20 patients studied, 12 (60%) were female. The most common etiologic agents were Staphylococcus aureus, in 5 patients (25%), and Klebsiella sp., in 2 (10%). The indications for surgery were sepsis, in 16 patients (80%), and bronchopleural fistula, in 4 (20%). The types of surgical procedures performed were lobectomy, in 12 patients (60%), segmentectomy, in 7 (35%), and bilobectomy, in 1 (5%). There were 8 patients (40%) who also underwent decortication. The postoperative complications were as follows: bronchopleural fistula, in 4 patients (20%); empyema, in 1 (5%); pneumatocele, in 1 (5%); and phlebitis of the left arm, in 1 (5%). Four (20%) of the patients died. Conclusions: Surgical resection should be considered in patients with evidence of pulmonary necrosis. Resection is indicated in cases of severe sepsis, high output bronchopleural fistula, or acute respiratory failure that are refractory to clinical treatment.

Keywords: Pneumonia; Necrosis; Lung abscess; Empyema, pleural.