Objective: Wegener's granulomatosis (WG) can cause endothelial cell damage and thromboembolic events. Nevertheless, there have been few studies on the pulmonary microcirculation-small and medium-sized pulmonary arteries (SMSPA)-in patients with WG. The objective of this study was to quantify fibrin thrombi in the SMSPA of patients with WG. Methods: We analyzed 24 SMSPA samples collected from six patients with WG and 16 SMSPA samples collected from four patients without WG. In all samples, we used the endothelial cell marker CD34 and confocal laser scanning microscopy in order to detect intravascular fibrin thrombi. We calculated the total vessel area, the free lumen area, and the thrombotic area. Results: The mean total vessel area was similar in the WG and control groups (32,604 µm2 vs. 32,970 µm2, p = 0.8793). Thrombi were present in 22 (91.67%) of the 24 WG group samples and in none of the control group samples (p < 0.0001; OR = 297; 95% CI: 13.34-6,612). The mean thrombotic area was greater in the WG group samples than in the control group samples (10,068 µm2 vs. 0.000 µm2; p < 0.0001). In contrast, the mean free lumen area was smaller in the WG group samples than in the control group samples (6,116 µm2 vs. 24,707 µm2; p < 0.0001). Conclusions: Confocal laser scanning microscopy revealed a significant association between pulmonary microvascular thrombosis and WG. This suggests a possible role of microvascular thrombosis in the pathophysiology of pulmonary WG, evoking the potential benefits of anticoagulation therapy in pulmonary WG. However, further studies are needed in order to confirm our findings, and randomized clinical trials should be conducted in order to test the role of anticoagulation therapy in the treatment of patients with pulmonary WG.

Keywords: Vasculitis; Antibodies, antineutrophil cytoplasmic; Wegener granulomatosis; Thrombosis; Lung; Microscopy, confocal.

Objective: To determine the incidence of the reversed halo sign (RHS) in patients with pulmonary infarction (PI) due to acute pulmonary embolism (PE), detected by computed tomography angiography (CTA) of the pulmonary arteries, and to describe the main morphological features of the RHS. Methods: We evaluated 993 CTA scans, stratified by the risk of PE, performed between January of 2010 and December of 2014. Although PE was detected in 164 scans (16.5%), three of those scans were excluded because of respiratory motion artifacts. Of the remaining 161 scans, 75 (46.6%) showed lesions consistent with PI, totaling 86 lesions. Among those lesions, the RHS was seen in 33 (38.4%, in 29 patients). Results: Among the 29 patients with scans showing lesions characteristic of PI with the RHS, 25 (86.2%) had a single lesion and 4 (13.8%) had two, totaling 33 lesions. In all cases, the RHS was in a subpleural location. To standardize the analysis, all images were interpreted in the axial plane. Among those 33 lesions, the RHS was in the right lower lobe in 17 (51.5%), in the left lower lobe in 10 (30.3%), in the lingula in 5 (15.2%), and in the right upper lobe in 1 (3.0%). Among those same 33 lesions, areas of low attenuation were seen in 29 (87.9%). The RHS was oval in 24 (72.7%) of the cases and round in 9 (27.3%). Pleural effusion was seen in 21 (72.4%) of the 29 patients with PI and the RHS. Conclusions: A diagnosis of PE should be considered when there are findings such as those described here, even in patients with nonspecific clinical symptoms.

Keywords: Pulmonary embolism; Pulmonary infarction; Computed tomography angiography.

We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

Keywords: Lung; Granuloma, foreign-body; Cocaine-related disorders.

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Keywords: Bronchoscopy; Tuberculosis, pulmonary; Sputum; Bronchoalveolar lavage; Biopsy.

Bronchocentric granulomatosis is histopathologically defined as being characterized by necrotizing granulomatous inflammation centered in the bronchi or bronchioles, which can be idiopathic or associated with infectious, immunologic or neoplastic diseases. This paper reports the case of a 26 year old nonasthmatic young woman with a 1-month history of chest pain, fever and productive cough. Chest radiography and computerized tomography were performed, and an open-lung biopsy was submitted to histological analysis. Radiographs and tomographs revealed consolidation and cavitation in the lingula. Transbronchial needle aspiration showed nonspecific inflammatory lesions, and no etiologic agent was identified. Histological examination of the specimen obtained by open-lung biopsy was consistent with idiopathic bronchocentric granulomatosis. The patient responded positively to prednisone therapy, and no relapse was documented.

Keywords: Bronchocentric granulomatosis. Bronchi. Allergic bronchopulmonary aspergillosis. Prednisone/therapeutic use.

Objective: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. Methods: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. Results: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. Conclusions: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

Keywords: Neuroendocrine tumors/lung; Microscopy, electron; Cluster analysis; Survival analysis.

Wegener's granulomatosis is a multisystemic inflammatory illness of unknown etiology, characterized by vasculitis of small and medium caliber vessels. The most common clinical manifestations involve the upper respiratory tract, lungs and kidneys. Common alterations in imaging studies include pulmonary opacities and bilateral multiple nodules, cavitations occurring in 50% of the cases. Treatment includes corticosteroids and immunosuppressants. We describe an atypical case of a 61-year-old man initially investigated due to suspicion of a unilateral lung tumor, which proved to be, in fact, a case of Wegener's granulomatosis.

Keywords: Wegener's Granulomatosis; Vasculitis; Diagnosis, differential; Lung neoplasms.

Abstract Objective: To compare four laboratory methods in the diagnosis of pulmonary tuberculosis. Methods: Respiratory secretion specimens were collected from 160 patients suspected of having pulmonary tuberculosis. Direct testing for Mycobacterium tuberculosis was carried out using Ziehl-Neelsen staining, auramine staining, culture on Löwenstein-Jensen (LJ) medium and polymerase chain reaction (PCR). The strains isolated were identified by means of a radiometric method using p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) and classical methods. The sensitivity of the methods was compared to the gold standard for the diagnosis of pulmonary tuberculosis, based on clinical, radiological and microbiological criteria. Results: Of the 160 patients, 142 were diagnosed with pulmonary tuberculosis according to the gold standard. The sensitivity of Ziehl-Neelsen staining, auramine staining, culture on LJ medium and PCR was 54.2%, 58.4%, 67.6% and 77.5%, respectively, when compared with the diagnostic criterion adopted. All four methods presented 100% specificity. In the identification of mycobacteria, there was high (96.8%) concordance between PCR and the radiometric method using NAP. The sensitivity of PCR was 50.8% in samples with negative sputum smear microscopy results and 98.8% in those with positive results. The sensitivity of PCR was lower in specimens with negative results in sputum smear microscopy and culture than in those with positive results (25.6% and 99.0%, respectively). Conclusions: We found PCR to be a promising method for the diagnosis of pulmonary tuberculosis, even in paucibacillary specimens. Simultaneous identification and faster results are additional advantages of this method.

Keywords: Tuberculosis, pulmonary/diagnosis; Culture media; Polymerase chain reaction; Sputum/microbiology.

Objective: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. Methods: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). Results: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). Conclusions: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

Keywords: Kidney transplantation; Immunosuppression therapy; Pneumonia.

Objective: To outline the prevalence of smoking in the city of Parazinho, Brazil, with the objective of generating data on which to base a plan of action for smoking control programs in the city. Methods: A questionnaire was applied to 150 people (25.6% of whom were smokers) by community health agents during home visits. The questionnaire comprised 30 objective and subjective questions to collect social and biological information on smokers in urban and rural areas. Results: The data were analyzed using descriptive statistics, and the principal findings were as follows: the prevalence of smoking was higher among males (57.8%); most of the interviewees started smoking at an early age (45% before the age of 12); economic conditions constituted a contributing factor (66% of the smokers interviewed earned less than the minimum wage); most of the interviewees reported difficulty in kicking the habit (44.6% reported living with a smoker, and 80% had a friend who smoked); there was a high prevalence of tobacco-related diseases (56.6% had respiratory problems); and there was concomitant alcohol use in 52% of the smokers. Conclusion: This outline can be used in the generation of a local program of smoking prevention and control. Such a program is, in fact, under development. A team of professionals has received training in a 'minimal, intensive approach to the smoker', and a municipal outpatient clinic for the treatment of nicotine dependence has been inaugurated.

Keywords: Smoking/prevention & control; Questionnaires; Smoking/epidemiology.

Objective: EBUS-TBNA cytological sampling is routinely performed for pathological diagnosis, mediastinal staging, and molecular testing in lung cancer patients. EBUS-TBNA samples are not formally accepted for testing programmed death-ligand 1 (PD-L1) expression. The objective of the study was to compare the feasibility, reproducibility, and accuracy of PD-L1 expression assessment in cytological specimens and histological samples. Methods: We prospectively collected histological (transbronchial forceps biopsy) and cytological (EBUS-TBNA) samples from peribronchial neoplastic lesions during an endoscopic procedure at the same target lesion for the pathological diagnosis and molecular assessment of stage IV non-small cell lung cancer (NSCLC). Results: Fifteen patients underwent the procedure. Adequate cytological samples (at least 100 neoplastic cells) were obtained in 12 cases (92.3%). Assessment of PD-L1 expression was similar between histological and cytological samples (agreement rate = 92%). Sensitivity and diagnostic accuracy of EBUS-TBNA cytological specimens were 88.9% and 100%, respectively. Conclusions: The evaluation of PD-L1 expression in EBUS-TBNA cytological specimens is feasible and presents good reproducibility when compared with routine histological samples. EBUS-TBNA cytological samples could be used for the assessment of PD-L1 expression in patients with NSCLC as a minimally invasive approach in stage IV NSCLC cancer patients.

Keywords: Ultrasonography; Biopsy, needle; Lung neoplasms; Molecular targeted therapy.

Objective: To evaluate small airway disease in COVID-19 patients using the prevalence of air trapping (AT) and correlating it with clinical outcomes. The relationship between CT-based opacities in small blood vessels and ventilation in patients with SARS-CoV-2 pneumonia was also assessed. Methods: We retrospectively included 53 patients with positive RT-PCR results for SARS-CoV-2 between March and April of 2020. All subjects underwent HRCT scanning, including inspiratory and expiratory acquisitions. Subjects were divided into two groups based on visual identification of AT. Small blood vessel volumes were estimated by means of cross-sectional areas < 5 mm2 (BV5) derived from automated segmentation algorithms. Mixed-effect models were obtained to represent the BV5 as a function of CT-based lobar opacities and lobar ventilation. Results: Of the 53 participants, AT was identified in 23 (43.4%). The presence of AT was associated with increased SpO2 at admission (OR = 1.25; 95% CI, 1.07-1.45; p = 0.004) and reduced D-dimer levels (OR = 0.99; 95% CI, 0.99-0.99; p = 0.039). Patients with AT were less likely to be hospitalized (OR = 0.27; 95% CI, 0.08-0.89; p = 0.032). There was a significant but weak inverse correlation between BV5 and CT-based lobar opacities (R2 = 0.19; p = 0.03), as well as a nonsignificant and weak direct correlation between BV5 and lobar ventilation (R2 = 0.08; p = 0.54). Conclusions: AT is a common finding in patients with COVID-19 that undergo expiratory CT scanning. The presence of AT may correlate with higher SpO2 at admission, lower D-dimer levels, and fewer hospitalizations when compared with absence of AT. Also, the volume of small pulmonary vessels may negatively correlate with CT opacities but not with lobar ventilation.

Keywords: SARS-CoV-2; COVID-19; Tomography, X-ray.

Background: Pulmonary thromboembolism (PTE) is still an enigmatic disorder in many epidemiological and clinical features, remaining one of the most commonly misdiagnosed disorders. Objective: To describe the prevalence and pathological findings of PTE in a series of autopsies, to correlate these findings with underlying diseases, and to verify the frequency of PTE clinically suspected before death. Method: The reports on 5261 consecutive autopsies performed from 1979 to 2002 in a Brazilian tertiary referral medical school were reviewed for a retrospective study. From the medical records and autopsy reports of the patients found with macroscopically and/or microscopically documented PTE, were gathered data on demographics, underlying diseases, antemortem suspicion of PTE, and probable PTE site of origin. Results: The autopsy rate was 42.0% and PTE was found in 544 patients. In 225 cases, PTE was the main cause of death (fatal PTE). Infections (p=0.0003) were associated with nonfatal PTE and trauma (p=0.007) with fatal PTE. The rate of antemortem unsuspected PTE was 84.6% and 40.0% of these patients presented fatal PTE. Diseases of the circulatory system (p=0.0001), infections (p<0.0001), diseases of the digestive system (p=0.0001), neoplasia (p=0.024) and trauma (p=0.005) were associated with unsuspected PTE. The most frequent PTE site of origin was the lower limbs (48.9%). Probable PTE sites of origin such as right-sided cardiac chambers (p=0.012) and pelvic veins (p=0.015) were associated with fatal PTE. Conclusion: A large number of cases do not have antemortem suspicion of PTE. Special attention should be paid to the possibility of PTE in patients with diseases of the circulatory system, infections, diseases of the digestive system, neoplasia, and trauma.

Keywords: Autopsy. Epidemiology. Pulmonary Thromboembolism.

Objective: To compare clinical, radiological, and laboratory characteristics of individuals with pulmonary tuberculosis co-infected or not with HIV. Methods: A cross-sectional study, in which signs and symptoms were assessed by anamnesis and physical examination in patients hospitalized with pulmonary tuberculosis. The results of sputum smear microscopy and culture for Mycobacterium tuberculosis, as well as hemoglobin levels and CD4+ T-cell counts, were obtained from medical records, and chest X-ray reports were consulted. Results: We included 50 pulmonary tuberculosis patients, who were divided into two groups (HIV-positive and HIV-negative; n = 25 per group). The mean age of the participants was 38.4 ± 10.5 years; 46 (92%) were males; and 27 (54%) were White. Expectoration was presented by 21 (84%) and 13 (52%) of the patients in the HIV-negative and HIV-positive groups, respectively (p = 0.016). Radiological findings of cavitation were present in 10 (43%) and 2 (10%) of the patients in the HIV-negative and HIV-positive groups, respectively (p = 0.016), whereas an interstitial pattern was observed in 18 (78%) and 8 (40%), respectively (p = 0.012). The mean hemoglobin level was 11.1 ± 2.9 g/dL and 9.3 ± 2.2 g/dL in the HIV-negative and HIV-positive groups, respectively (p = 0.015). Conclusions: In our sample of tuberculosis patients, expectoration was less prevalent, hemoglobin levels were lower, and cavitation was less common, as was an interstitial pattern, among those co-infected with HIV than among those without HIV co-infection.

Keywords: HIV; Tuberculosis; Acquired immunodeficiency syndrome.

Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 [95% CI: 1.3-9.86]; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 [95% CI: 1.57-25.21]; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

Keywords: Tuberculosis; Treatment outcome; Smoking.