Objective: This study aimed to determine the serum levels of NACHT, Leucine-rich repeat (LRR), and Pyrin (PYD) domains-containing Protein 3 (NLRP3) and cathelicidin LL-37, and investigate their prognostic significance in community-acquired pneumonia (CAP). Methods: The sample of this prospective study was composed of 76 consecutive patients with CAP. Demographic data and clinical characteristics were collected. Serum levels of NLRP3 and LL-37 were determined by ELISA. Spearman's analysis was used to evaluate the correlation between NLRP3 and LL-37. Association of NLRP3 and LL 37 with 30-day survival and mortality rates was assessed using the Kaplan-Meier curve and logistic regression analysis. Results: Serum NLRP3 significantly increased whereas serum LL-37 significantly decreased in patients with severe CAP. Significant correlation was observed between serum NLRP3 and LL-37 in CAP patients. Patients with higher levels of NLRP3 and lower levels of LL-37 showed lower 30-day survival rate and higher mortality compared with those with lower NLRP3 and higher LL-37 levels. Conclusion: Severe CAP patients tend to present higher serum NLRP3 and lower serum LL-37, which might serve as potential biomarkers for CAP prognosis.

Keywords: Community-acquired pneumonia; Prognosis; Biomarkers; Prospective study.

A significant percentage of pleural effusions remains without a diagnostic explanation. In such circumstances, the anatomical-pathological result of nonspecific chronic pleuritis should be revised. This is an important issue, not only for the pathologist, but mainly for the pneumologist, who usually makes the clinical-pathological correlation during the routine practice. Although the existence of established criteria is accepted, they are certainly subjective and make the communication by means of a common language difficult, mainly among pathologists. The authors recently studied 311 pleural biopsies with histo-pathological diagnoses of chronic nonspecific pleuritis. All specimens were reviewed and the histo-pathological parameters quantified by stereology. The patients were stratified according to the final diagnosis of their disease, including cases of chronic renal failure, vasculitis, pancreatitis, tuberculosis, cancer, and congestive cardiac failure, in this case considering the pleura as normal. This procedure allowed us to obtain a discriminating model, whose morphological subcriteria classified almost 90% of the nonspecific chronic pleuritis biopsies, according to their final clinical diagnoses, which included true nonspecific chronic pleuritis or tuberculosis pleuritis, paraneoplastic pleuritis, or even normal pleura. By adding to this model the biochemistry or differential cytology of the pleural liquid, its classificatory power reaches 99% of correctness. This study represents the result of the experience acquired over several years in the histo-pathological interpretation of pleural biopsies, based on the correlation between morphology and biochemistry and cytology of the pleural fluid.

Keywords: Biopsy, needle. Pleura/pathology. Pleura/cytology. Pleural effusion.

Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

Keywords: Phosphopyruvate hydratase/analysis; Enzyme-linked immunosorbent assay; Immunohistochemistry; Lung neoplasms.

Objective: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. Methods: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). Results: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. Conclusions: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination.

Keywords: Pulmonary disease, chronic obstructive/epidemiology; Acute disease; Acute-phase proteins; Hospitalization; Patient readmission; Inflammation.

Objective: To correlate the postbronchodilator (post-BD) inspiratory capacity (IC), % of predicted, with other markers of severity and prognostic factors in chronic obstructive pulmonary disease (COPD). Methods: Eighty stable patients with COPD performed forced vital capacity and slow vital capacity maneuvers, as well as the 6-min walk test, prior to and after receiving albuterol spray (400 μg). Patients were divided into four groups, based on post-BD forced expiratory volume in one second. Several variables were tested to establish correlations with the post-BD distance walked, using univariate and multivariate analysis. Post-BD IC was found to correlated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and with the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index. Results: Multivariate regression analysis revealed that the distance walked, % predicted, correlated significantly with the IC post-BD, % predicted (p = 0.001), long-term oxygen use (p = 0.014), and number of medications used in the treatment (p = 0.044). IC ≤ 70% was observed in 56% patients in GOLD stages 3 or 4 vs. 20% in GOLD 1 or 2 (p < 0.001). IC ≤ 70% was observed in (60%) patients with BODE score 3 or 4 vs. (33%) BODE score 1 or 2 (p = 0.02). Conclusion: Post-BD IC% predicted is the best functional predictor of distance walked and is significantly associated with GOLD staging and BODE index. Therefore, We propose that the inspiratory capacity should be added to the routine evaluation of the COPD patients.

Keywords: Pulmonary disease, chronic obstructive; Walking; Respiratory function tests; Inspiratory capacity.

Objective: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. Methods: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. Results: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre‑and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. Conclusions: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br])

Keywords: Lymphangioleiomyomatosis; Doxycycline; Matrix metalloproteinases; Respiratory function tests.

Objective: To evaluate the diagnostic performance of the rapid shallow breathing index (RSBI) in predicting extubation failure among adult patients in the intensive care unit and to determine the appropriateness of the classical RSBI cut-off value. Methods: This was a prospective study conducted in the adult intensive care unit of the Botucatu School of Medicine Hospital das Clínicas. The RSBI was evaluated in 73 consecutive patients considered clinically ready for extubation. Results: The classical RSBI cut-off value (105 breaths/min/L) presented a sensitivity of 20% and a specificity of 95% (sum = 115%). Analysis of the receiver operator characteristic (ROC) curve revealed a better cut-off value (76.5 breaths/min/L), which presented a sensitivity of 66% and a specificity of 74% (sum = 140%). The area under the ROC curve for the RSBI was 0.78. Conclusions: The classical RSBI cut-off value proved inappropriate, predicting only 20% of the cases of extubation failure in our sample. The new cut-off value provided substantial improvement in sensitivity, with an acceptable loss of specificity. The area under the ROC curve indicated that the discriminative power of the RSBI is satisfactory, which justifies the validation of this index for use.

Keywords: Adult; Intensive care; ROC curve; Ventilator weaning; Diagnosis; Respiration, artificial.

Objective: Ventilator-associated pneumonia (VAP) is the leading type of hospital-acquired infection in ICU patients. The diagnosis of VAP is challenging, mostly due to limitations of the diagnostic methods available. The aim of this study was to determine whether antibody-coated bacteria (ACB) evaluation can improve the specificity of endotracheal aspirate (EA) culture in VAP diagnosis. Methods: We conducted a diagnostic case-control study, enrolling 45 patients undergoing mechanical ventilation. Samples of EA were obtained from patients with and without VAP (cases and controls, respectively), and we assessed the number of bacteria coated with FITC-conjugated monoclonal antibodies (IgA, IgM, or IgG) or an FITC-conjugated polyvalent antibody. Using immunofluorescence microscopy, we determined the proportion of ACB among a fixed number of 80 bacteria. Results: The median proportions of ACB were significantly higher among the cases (n = 22) than among the controls (n = 23)-IgA (60.6% vs. 22.5%), IgM (42.5% vs. 12.5%), IgG (50.6% vs. 17.5%), and polyvalent (75.6% vs. 33.8%)-p < 0.001 for all. The accuracy of the best cut-off points for VAP diagnosis regarding monoclonal and polyvalent ACBs was greater than 95.0% and 93.3%, respectively. Conclusions: The numbers of ACB in EA samples were higher among cases than among controls. Our findings indicate that evaluating ACB in EA is a promising tool to improve the specificity of VAP diagnosis. The technique could be cost-effective and therefore useful in low-resource settings, with the advantages of minimizing false-positive results and avoiding overtreatment.

Keywords: Pneumonia, ventilator-associated/diagnosis; Immunohistochemistry; Fluorescent antibody technique; Antibodies, bacterial/analysis; Trachea/microbiology; Intensive care units.

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Keywords: Molecular targeted therapy; Receptor, epidermal growth factor; Lung neoplasms/drug therapy; Mutation; Oncogenes.

Despite the improvements seen in the treatment of lung cancer, little has improved in the survival of these patients, and a great importance is attributed to the factors that have a role to play in such survival. Purpose: To check for possible prognostic factor differences in two populations of lung cancer patients, one of them with short survival (less than six months), and the other with longer survival (more than 24 months). Methods: From 1997 to 1999, 52 patients with histopathologic diagnosis of homogenous carcinoma were studied, and demographics, clinical parameters, smoking pattern, Karnofsky's index, disease staging, and laboratory dosing of lactic dehydrogenase, alkaline phosphatase, carcinoembryonic antigen, and calcium data were surveyed. Results: 29 patients had less than six month survival, and 23 had more than 24 month survival. The three most important factors for short survival were the low initial Karnofsky's index, loss of appetite, and high serum LDH levels. Conclusion: The three prognosis components are: current physical status, prior physical status, and current status of the disease.

Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

Keywords: Smoking; Lung neoplasms; Genetic markers; Prognosis

Objective: To determine the absolute number of serum T lymphocytes and cytokine levels and the characteristics of patients with active pulmonary tuberculosis and to assess their effect on the immune status of these patients and their diagnostic and predictive value for tuberculosis. Methods: We included 1,069 patients with active tuberculosis, 51 patients with latent tuberculosis infection, and 600 health individuals. Absolute serum T-lymphocyte counts and cytokine levels were quantified. Results: T lymphocytes were significantly reduced in patients with active tuberculosis when compared with healthy individuals. The immune function of patients gradually decreased with age and was stronger in female patients than in males. Th1 cells expressed higher levels of cytokines than did Th2 cells. Logistic regression analysis showed that reduced CD3+ T, CD8+ T, and NK cell counts, as well as reduced IL-4 and IFN-? expression, were independent influencing factors for active tuberculosis. ROC analysis showed that the sensitivity and specificity of absolute CD3+ T and CD8+ T lymphocyte counts and combined factors were significantly higher than were those of IL-4 and IFN-? for diagnosing active tuberculosis. Conclusions: Serum T-lymphocyte counts and cytokine levels can assess the immune status of tuberculosis patients; they are also useful biomarkers for predicting and diagnosing tuberculosis.

Keywords: Lymphocytes; Cytokines; Tuberculosis; Immunity.

The World Health Organization (WHO) has recently recommended new technologies for the diagnosis of tuberculosis. The WHO recommendations include the development of a strategic plan for bringing the network up to grade; investment in supervision and quality control; and implementation of a system of laboratory environmental management. Without those measures having been taken, no new technology can be effectively incorporated. We surveyed the tuberculosis laboratory network in Brazil in order to identify possible bottlenecks for the incorporation of new technologies. We identified a lack of resources allocated to supervision and quality control; a low number of requests for cultures; a lack of effective laboratory information systems; and a lack of awareness regarding the future infrastructure needs of the laboratory network at the municipal level.

Keywords: Quality control; Tuberculosis; Laboratories; Clinical laboratory information systems; Technology

Objective: To estimate the prevalence of current commercial cigarette smoking, as well as those of e-cigarette and hookah experimentation and current use among adults (= 18 years of age) in Brazil. Methods: This study was based on a countrywide cross-sectional telephone-based survey conducted in 2022. The sample was designed to be representative of the five macroregions in Brazil and included 1,800 individuals from each of the regions. Telephone numbers, using a random digit dialing procedure, were proportionally selected for each direct distance dialing code in each region and then electronically validated (i.e., 900 cell and 900 landline phone numbers per region). Information on current commercial cigarette smoking (regardless of frequency/amount), as well as lifetime history of or current e-cigarette and hookah use (regardless of amount), were collected. Results: The prevalence of lifetime history of e-cigarette and hookah use was identical (7.3%; 95% CI: 6.0-8.9), whereas the prevalence of current commercial cigarette smoking was 12.2% (95% CI: 10.4-14.1). Young adults (18-24 years) had the highest prevalence of e-cigarette experimentation (19.7%; 95% CI: 15.1-17.0) and hookah experimentation (17%; 95% CI: 12.2-23.2). E-cigarette and hookah use was more common in the Central-West region and among those with a high level of education, whereas current commercial cigarette smoking was more common among those with a lower level of education. Individuals who used the three forms of nicotine delivery corresponded to 1.5% of the sample (nearly 2 million individuals based on the estimated size of the Brazilian adult population). Conclusions: Surveillance is essential for the monitoring and prevention of these new forms of nicotine consumption.

Keywords: Electronic nicotine delivery systems; Smoking water pipes; Nicotine; Tobacco products; Adults.

Objective: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. Methods: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. Results: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (= 1 point) and C scores (= 4 points) were 12.5% and 81.8%, respectively. Conclusions: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

Keywords: Sarcoidosis; Prognosis; Chronic disease; Tuberculosis.