Objective: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. Methods: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. Results: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = −0.90; p = 0.04). Conclusions: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Keywords: Sarcoidosis; Granulomatous disease, chronic; Extracellular matrix; Immunophenotyping; Respiratory function tests.

Coccidioidomycosis, a fungal illness acquired by the inhalation of arthroconidia of Coccidioides sp., was first described in 1894. Coccidioidomycosis is mainly restricted to areas with arid climate, alkaline soil and low rainfall. Consequently, most of the reported cases in Brazil have occurred in the northeastern region. We report three cases of pulmonary coccidioidomycosis occurring between 2005 and 2006 in an endemic area in the state of Ceará, Brazil. The three patients were immunocompetent adult males, hunters of armadillos (Dasypus novemcinctus), with complaints of cough, fever, dyspnea and pleuritic pain. All three patients presented pulmonary involvement, and one also presented cutaneous lesions. Chest X-rays and CT scans of the patients revealed characteristic coccidioidomycosis lesions. The diagnosis was confirmed by serological testing. All of the patients evolved to cure after antifungal treatment.

Keywords: Coccidioidomycosis; Lung diseases, fungal; Coccidioides.

Objective: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. Methods: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. Results: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). Conclusions: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis.

Keywords: Tuberculosis/diagnosis; Tuberculosis/microbiology; Mycobacterium tuberculosis; Polymerase chain reaction.

Background: Structural alterations to the pulmonary circulation characterize the vascular remodeling process and are likely correlated with local variations in flow and ischemia. Objective: To define the histological alterations to the pulmonary circulation seen after experimentally-induced ischemia of the pulmonary artery and to correlate those alterations with known patterns of blood redistribution and vascular remodeling. Method: Wistar rats (n = 48) were randomized into two groups with ligation of the pulmonary artery and without (controls) and were sacrificed on post-ischemia days 1, 7, 30 and 60. Lungs were removed and inspected for signs of parenchymal injury. External diameters, as well as wall thicknesses in the pulmonary, alveolar and bronchial end arterioles, were measured. Internal diameter and wall thickness percentage were calculated. Results: Infarction, necrosis and hemorrhage occurred only in ischemic lungs. In nonischemic lungs, there was a sustained increase in the internal and external arteriolar diameters, with an initial reduction in wall thickness on day 1, and day-60 values were similar to those seen in controls. In ischemic lungs, there was a transitory reduction in the internal and external diameters of the pulmonary and bronchial end arterioles, together with an initial, equally transitory, increase in their wall thickness. The alveolar arterioles presented sustained and progressive increases in external diameter and wall thickness, with concomitant reductions in internal diameter. Conclusion: This model mimics distal arterial disease in patients with chronic pulmonary thromboembolism. The vascular response in nonischemic lungs was consistent with a pattern of flow remodeling, whereas that seen in ischemic lungs was more consistent with flow and ischemia. In the pulmonary and bronchial end arterioles, the response was transitory, in contrast to the sustained and progressive response seen in the alveolar arterioles, which was probably caused by delayed local flow.

Keywords: Key-words: Pulmonary embolism. Pulmonary circulation. Vascular remodelling. Pulmonary artery.

Objective: To investigate the effects of maternal protein malnutrition during lactation on the elastic fibers in the tracheas of Wistar rat pups. Methods: At delivery, 12 male pups of two Wistar rat dams were equally divided into two groups: control, in which the dam received water and standard rat chow ad libitum during lactation; and protein-restricted (PR), in which the dam received water ad libitum and an isoenergetic PR diet (8% protein). At 21 days of age, the pups were killed and their tracheas were excised. The elastic fibers were stained with Weigert's resorcin-fuchsin (after oxidation) and evaluated under light microscopy. Morphometric determinations were performed by stereology, with the point-counting method, and expressed as volumetric densities. Results: Elastic fibers, most having a longitudinal distribution, were identified beneath the tracheal mucosa. In addition, well-defined circular layers of elastic fibers were found around the inner and outer surfaces of the cartilaginous ring. There were no differences between the groups regarding the organization and distribution of the elastic fibers. The volumetric density of the elastic fibers of the pups in the control and PR groups was 2.46 ± 0.99% and 3.25 ± 1.13%, respectively (p < 0.01). Conclusions: The volumetric density of elastic fibers appears to be greater in rat pups breastfed by dams receiving a PR diet than in those breastfed by dams receiving a normal diet.

Keywords: Trachea/growth and development; Trachea/anatomy and histology; Extracellular matrix; Airway remodeling; Malnutrition.

Objetivo: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. Métodos: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. Resultados: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vγ11/Jγ12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dβ1/Jβ2 e Vγ101/Jγ12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. Conclusões: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnósticObjetivo: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. Métodos: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. Resultados: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vγ11/Jγ12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dβ1/Jβ2 e Vγ101/Jγ12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. Conclusões: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnóstica.

Keywords: Linfoma; Doenças pulmonares intersticiais; Biologia molecular; Reação em cadeia da polimerase.

The relationship between structure and function in asthma has been extensively studied. All the compartments of the airway have been shown to have some structural alterations contributing to functional defects. The structural alterations are thought to be a consequence of the chronic inflammation present in asthmatic airways, leading ultimately to remodeling. The decline of the ventilatory function over time in some asthmatic patients may be a consequence of airway remodeling. In this review, the authors describe the phenomena leading to airway remodeling and discuss the role of inflammatory mediators involved in this process. The structural alterations of the asthmatic airways are presented and the possible correlated functional defects are discussed.

Keywords: bronchii; pathology; asthma.

Objective: Evaluation of enlarged mediastinal lymph nodes is crucial for patient management. Malignant lymphoma and sarcoidosis are often difficult to differentiate. Our objective was to determine the diagnostic accuracy of MRI for differentiating between sarcoidosis and malignant lymphoma. Methods: This was a retrospective study involving 47 patients who underwent chest MRI and were diagnosed with one of the diseases between 2017 and 2019. T1, T2, and diffusion-weighted signal intensity were measured. Apparent diffusion coefficients (ADCs) and T2 ratios were calculated. The diagnostic performance of MRI was determined by ROC analysis. Results: Mean T2 ratio was significantly lower in the sarcoidosis group than in the lymphoma group (p = 0.009). The T2-ratio cutoff value that best differentiated between lymphoma-related and sarcoidosis-related enlarged lymph nodes was 7.1, with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 58.3%, 95.6%, 76.5%, 93.3%, and 68.7%, respectively. The mean ADC was significantly lower in the lymphoma group than in the sarcoidosis group (p = 0.002). The ADC cutoff value that best differentiated between lymphoma-related and sarcoidosis-related enlarged lymph nodes was 1.205, with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 87.5%, 82.6%, 85.1%, 84.0% and 86.3%, respectively. No significant differences were found between the two groups regarding T1 signal intensity, T2 signal intensity, and lymph node diameter. Conclusions: MRI parameters such as ADC, diffusion, and T2 ratio can be useful in the differentiation between sarcoidosis and lymphoma in the evaluation of enlarged lymph nodes.

Keywords: Diffusion magnetic resonance imaging; Lymphoma; Lymph nodes; Sarcoidosis.

Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management.

Keywords: Sarcoidosis; Joints; Muscles; Bone and Bones.

Acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibroproliferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient's prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

Keywords: Respiratory distress syndrome. Pulmonary alveoli/lesions. Extracellular matrix. Cytokines/ultrastructure.

Pulmonary cavitation is rather uncommon in patients with sarcoidosis, and aspergilloma is even more uncommon in such cases. Here, we present the case of a 63-year-old female patient with cavitary lung disease who had been under treatment for TB for 9 months. A diagnosis of pulmonary sarcoidosis was established based on the fiberoptic bronchoscopy finding of noncaseating granuloma. Treatment with corticosteroids led to a dramatic improvement in symptoms. While under treatment for sarcoidosis, the patient developed an aspergilloma. She presented immediate skin test reactivity to Aspergillus fumigatus, as well as positivity for A. fumigatus serum precipitins. This is the first reported case of aspergilloma formation in a patient with cavitary sarcoidosis in India.

Keywords: Sarcoidosis, pulmonary; Aspergillosis; Medical records.

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.

Keywords: Sarcoidosis; Health status; Validation studies; Questionnaires; Self report; Serbia.

Although hemophagocytic syndrome is a rare clinical condition, it is associated with high mortality and the number of cases described in the literature has progressively increased. The diagnosis of hemophagocytic syndrome is made on the basis of a finding of hemophagocytosis. Sarcoidosis is a highly prevalent disease whose course and prognosis might correlate with the initial clinical presentation and the extent of the disease. We report the case of a patient with long-standing sarcoidosis who presented with intermittent fever and fatigue. The diagnosis of hemophagocytic syndrome was made by bone marrow aspiration, and specific treatment was ineffective. This is the third case of sarcoidosis-related hemophagocytic syndrome reported in the literature and the first reported in Latin America. All three cases had unfavorable outcomes.

Keywords: Lymphohistiocytosis, hemophagocytic; Ferritins; Sarcoidosis, pulmonary; Macrophage activation syndrome.

Sarcoidosis is a systemic disease of unknown etiology, characterized by noncaseating granulomas. Although it may affect any organ, morbidity and mortality are most commonly related to pulmonary involvement, which is found in 80-90% of patients. This study illustrates the principal manifestations of sarcoidosis seen in high-resolution computed tomography scans, including typical as well as atypical forms.

Keywords: Sarcoidosis. Lung. High-resolution computed tomography.

Objective: To describe the clinical and functional findings recently reported in the medical literature for patients diagnosed with emphysema involving the upper lobes and idiopathic pulmonary fibrosis (IPF) involving the lower lobes. Methods: Eleven patients with emphysema and IPF were identified retrospectively. All of the patients underwent high-resolution computed tomography of the lung and pulmonary function tests. Results: Of the 11 patients, 8 were male and 3 were female. The mean age was 70.7 ± 7.2 years (range, 61-86 years). All of the patients were smokers (mean smoking history, 61.5 ± 43.5 pack-years). The mean values of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC were 72.1 ± 12.7%, 68.2 ± 11.9% and 74.4 ± 10.8, respectively. Lung volumes were normal in 7 patients. A restrictive pattern was observed in 3 patients, and hyperinflation was present in one. The diffusing capacity was moderatelyto- severely reduced in all of the patients (mean, 27.7% ± 12.9% of predicted). Ten of the 11 patients performed the six-minute walk test. The mean distance covered was 358.4 ± 143.1 m, and 9 of the 10 patients presented desaturation ≥ 4%. Echocardiographic findings suggestive of pulmonary hypertension were present in 4 patients (mean systolic pulmonary artery pressure, 61.8 mmHg; range, 36-84 mmHg). Conclusions: The concomitant presence of emphysema and IPF causes characteristic changes on pulmonary function tests. The most significant finding is a discrepancy between diffusing capacity and spirometry results.

Keywords: Pulmonary emphysema; Pulmonary fibrosis; Lung Diseases, interstitial; Anoxia; Hypertension, pulmonary.

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Keywords: Neoplasms; Lymphangioleiomyomatosis/therapy; TOR serine-threonine kinases; Sirolimus.