Type V collagen-induced nasal tolerance prevents lung damage in an experimental model: new evidence of autoimmunity to collagen V in COPD.

Background: Chronic obstructive pulmonary disease (COPD) has been linked to immune responses to lung-associated self-antigens. Exposure to cigarette smoke (CS), the main cause of COPD, causes chronic lung inflammation, resulting in pulmonary matrix (ECM) damage. This tissue breakdown exposes collagen V (Col V), an antigen typically hidden from the immune system, which could trigger an autoimmune response. Col V autoimmunity has been linked to several lung diseases, and the induction of immune tolerance can mitigate some of these diseases. Evidence suggests that autoimmunity to Col V might also occur in COPD; thus, immunotolerance to Col V could be a novel therapeutic approach. Objective: The role of autoimmunity against collagen V in COPD development was investigated by analyzing the effects of Col V-induced tolerance on the inflammatory response and lung remodeling in a murine model of CS-induced COPD. Methods: Male C57BL/6 mice were divided into three groups: one exposed to CS for four weeks, one previously tolerated for Col V and exposed to CS for four weeks, and one kept in clean air for the same period. Then, we proceeded with lung functional and structural evaluation, assessing inflammatory cells in bronchoalveolar lavage fluid (BALF) and inflammatory markers in the lung parenchyma, inflammatory cytokines in lung and spleen homogenates, and T-cell phenotyping in the spleen. Results: CS exposure altered the structure of elastic and collagen fibers and increased the pro-inflammatory immune response, indicating the presence of COPD. Col V tolerance inhibited the onset of emphysema and prevented structural changes in lung ECM fibers by promoting an immunosuppressive microenvironment in the lung and inducing Treg cell differentiation. Conclusion: Induction of nasal tolerance to Col V can prevent inflammatory responses and lung remodeling in experimental COPD, suggesting that autoimmunity to Col V plays a role in COPD development.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50 µl, 0.667 IU) to induce emphysema. Treatment with PNU-282987 (2.0 mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1ß, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

Relación entre la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica: revisión bibliográfica / Relationship between periodontal disease and chronic obstructive pulmonary disease: a bibliographic review

Introducción: la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica son patologías de origen inflamatorio crónico y progresivo que afectan a pacientes de edad avanzada, fumadores con mal estado de salud oral, encontrándose una correlación por el grado de severidad en la enfermedad periodontal sobre aquellos individuos con presencia de enfermedad pulmonar obstructiva crónica (EPOC) y exacerbaciones. Objetivos: determinar la relación de la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica, explicando los factores de riesgo que intervienen en estas enfermedades. Material y métodos: se realizó una búsqueda en los principales buscadores de datos digitales: PubMed, SciELO, Science Direct, BMC, Journal of Periodontology, Web of Science y Scopus. Se escogieron artículos publicados en los últimos cinco años; se excluyeron artículos incompletos y que no se relacionan al tema. En el resultado de la búsqueda, 45 artículos cumplieron con el propósito de la revisión bibliográfica. Resultados: en esta revisión bibliográfica, se obtuvo que 18 artículos comprueban la relación de la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica. Conclusiones: se ha comprobado la relación entre la enfermedad periodontal y enfermedad pulmonar obstructiva crónica. Se requiere el análisis de más estudios para determinar una relación directa entre estas dos enfermedades e incluir variables como la edad y el tratamiento (AU)

Introduction: periodontal disease and chronic obstructive pulmonary disease are diseases of chronic and progressive inflammatory origin that affect elderly patients, smokers with poor oral health, finding a correlation by the degree of severity in periodontal disease on those individuals with the presence of chronic obstructive pulmonary disease (COPD) and exacerbations. Objectives: to determine the relationship between periodontal disease and chronic obstructive pulmonary disease explaining the risk factors involved in these diseases. Material and methods: a search was carried out in the main digital data search engines: PubMed, SciELO, Science Direct, BMC, Journal of Periodontology, Web of Science, and Scopus, articles published in the last 5 years were chosen, incomplete articles and those not related to the subject were excluded, in the result of the search 45 articles fulfilled the purpose of the bibliographic review. Results: in this literature review it was obtained that 18 articles, prove the relationship between periodontal disease and chronic obstructive pulmonary disease. Conclusions: the relationship between periodontal disease and chronic obstructive pulmonary disease has been proved. More studies are needed to determine a direct relationship between these two diseases and to include variables such as age and treatment (AU)

Prevalence of genetic mutations in alpha-1 antitrypsin deficiency (aatd) in patients with chronic obstructive pulmonary disease in Colombia.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.

Síndrome combinado de fibrosis pulmonar y enfisema: albores del tratamiento antifibrótico en el Paraguay

La concomitancia de fibrosis pulmonar en regiones inferiores del pulmón y enfisema en lóbulos superiores caracterizan a una entidad poco frecuente denominada síndrome combinado de fibrosis pulmonar y enfisema, que usualmente se asocia a alta carga de tabaquismo, aunque se describen otras asociaciones y que conlleva un pronóstico sombrío. La hipertensión pulmonar, el cáncer de pulmón y la exacerbación aguda son complicaciones posibles. En el contexto de un enfoque multidisciplinar de manejo de tres casos, relatamos el curso del tratamiento con pirfenidona.

The concomitance of pulmonary fibrosis in the lower regions of the lung and emphysema in the upper lobes characterize a rare entity called combined pulmonary fibrosis and emphysema syndrome, which is usually associated with a high burden of smoking, although other associations have been described and which carries a poor prognosis. Pulmonary hypertension, lung cancer, and acute exacerbation are possible complications. In the context of a multidisciplinary approach to the management of three cases, we report the course of treatment with pirfenidone.

Treatments used by chronic obstructive pulmonary disease patients in Brazil: National Survey of Health, 2013 / Tratamentos utilizados por portadores de DPOC no Brasil: Pesquisa Nacional de Saúde, 2013

ABSTRACT OBJECTIVE To estimate the prevalence of treatments used for the management of chronic obstructive pulmonary disease (COPD) in the Brazilian adult population. METHODS A population-based cross-sectional study with data from the 2013 Brazilian National Survey of Health, including individuals aged 40 years or older, with a self-reported medical diagnosis of COPD, chronic bronchitis and/or emphysema, who were asked about treatments used for disease management. RESULTS A total of 60,202 adults were interviewed, of which 636 were 40 years of age or older and had reported a medical diagnosis of COPD, emphysema, or chronic bronchitis. Less than half (49.4%) of the diagnosed population reported using some type of treatment, with differences regarding the macro-region of the country (South 53.8% - Northeast 41.2%, p = 0.007). Pharmacological treatment was the most reported, and emphysema patients had the highest proportion of those undergoing more than one type of treatment. Among the individuals who reported having only chronic bronchitis, 55.1% (95%CI: 48.7-61.4) used medication, 4.7% (95%CI: 2.6-8.3) underwent physical therapy, and 6.0% (95%CI: 3.6-9.9) oxygen therapy. On the other hand, among the emphysema patients, 44.1% (95%CI: 36.8-51.7) underwent drug treatment, 8.8% (95%CI: 5.4-14.2) physical therapy, and 10.0% (95%CI: 6.3-15.6) oxygen therapy. CONCLUSION The prevalence of treatments for COPD management was below ideal in 2013. The pharmacological treatment was the main type of treatment, followed by oxygen therapy and physical therapy.

RESUMO OBJETIVO Estimar a prevalência dos tratamentos utilizados para o manejo da doença pulmonar obstrutiva crônica (DPOC) na população adulta brasileira. MÉTODOS Estudo transversal de base populacional com dados oriundos da Pesquisa Nacional de Saúde de 2013, incluindo indivíduos com 40 anos ou mais, com diagnóstico médico autorreferido de DPOC, bronquite crônica e/ou enfisema, os quais foram questionados sobre tratamentos utilizados para o manejo da doença. RESULTADOS Foram entrevistados 60.202 adultos, dos quais 636 tinham 40 ou mais anos de idade e haviam referido diagnóstico médico de DPOC, enfisema ou bronquite crônica. Menos da metade (49,4%) da população diagnosticada relatou utilizar algum tipo de tratamento, havendo diferenças quanto à macrorregião do país (Sul 53,8% - Nordeste 41,2%, p = 0,007). O tratamento medicamentoso foi o mais referido e portadores de enfisema apresentaram a maior proporção de mais de um tipo de tratamento utilizado. Entre os indivíduos que declararam ter apenas bronquite crônica, 55,1% (IC95% 48,7-61,4) usavam medicamento, 4,7% (IC95% 2,6-8,3) realizavam fisioterapia e 6,0% (IC95% 3,6-9,9) oxigenoterapia. Por outro lado, entre os enfisematosos, 44,1% (IC95% 36,8-51,7) realizavam tratamento medicamentoso, 8,8% (IC95% 5,4-14,2) fisioterapia e 10,0% (IC95% 6,3-15,6) oxigenoterapia. CONCLUSÕES As prevalências de tratamentos para o manejo da DPOC estavam aquém do ideal em 2013. O medicamentoso foi o principal tipo de tratamento, seguido de oxigenoterapia e fisioterapia.

Enfisema pulmonar congênito: relato de caso / Congenital pulmonary enphysema: case report

Introdução: O enfisema pulmonar congênito (EPC) é uma doença rara, possuindo uma incidência de 1:20-30 mil nascimentos, é mais comum no sexo masculino do que no feminino, em uma razão de 3:1 e sua etiologia permanece desconhecida. Um terço dos casos são sintomáticos ao nascer e praticamente todos são diagnosticados nos primeiros seis meses de vida. Relato de Caso: Recém-nascido (RN) do sexo masculino, evoluiu com desconforto respiratório precoce, sendo encaminhado ao centro de terapia intensiva. Após uso de continuous positive airway pressure (CPAP) e cateter nasal de oxigênio de 12 horas, resultou em bom padrão respiratório e boa saturação. Após realização de tomografia computadorizada, foi diagnosticado o EPC. Conclusão: O EPC é uma patologia rara e deve ser suspeitado em RN com desconforto respiratório, atribuindo-se importância aos vários diagnósticos diferenciais possíveis. Apesar da etiologia incerta, é de fácil diagnóstico e possui opções de manejo clínico e cirúrgico.

Introduction: Congenital pulmonary emphysema (EPC) is a rare disease, with an incidence of 1:20-30 thousand births, it is more common in males than in females, in a ratio of 3:1 and its etiology remains unknown. One third of the cases are symptomatic at birth and practically all are diagnosed in the first six months of life. Case Report: Newborn (NB) male, developed early respiratory distress, being referred to the intensive care unit. After using continuous positive airway pressure (CPAP) and a 12-hour oxygen nasal catheter, it resulted in a good breathing pattern and good saturation. After performing computed tomography, EPC was diagnosed. Conclusion: EPC is a rare pathology and should be suspected in newborns with respiratory distress, with importance being given to the various possible differential diagnoses. Despite its uncertain etiology, it is easy to diagnose and has options for clinical and surgical management.

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema.

Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD.

Small airway evaluation in three subjects with alpha-1 antitrypsin deficiency without diagnosed lung disease.

We describe three cases of female subjects (aged 16, 44 and 41 years) with no respiratory symptoms, who have alpha-1 antitripsyn mutation (PiSZ, PiZZ and PiZZ) and who performed traditional pulmonary function tests and the single breath nitrogen washout test. They still did not have chronic obstructive pulmonary disease (COPD) or any identifiable change in traditional pulmonary function tests but already have change in nitrogen washout tests. Alpha-1 antitrypsin deficiency is a genetic disorder associated with early-onset COPD. There is evidence that although patients who have well-preserved FEV1 may already have signs of emphysema associated with symptoms. Therefore, the nitrogen washout test is considered to have more sensitive outcomes than other pulmonary function tests for early investigation of small airways disease and could allow the monitoring pulmonary function and evaluating of therapeutic decision.

Neumotórax espontáneo y enfisema bulloso bilateral / Spontaneous pneumothorax and bilateral bullous emphysema

Introducción. El objetivo de este artículo fue reportar el caso de un paciente con antecedente de enfisema bulloso bilateral que le ocasionó un neumotórax persistente de difícil tratamiento. Caso clínico. Se trata de un paciente de 50 años de edad con diagnóstico de neumotórax asociado con un enfisema bulloso bilateral, en quien estaba contraindicado el tratamiento quirúrgico. El cuadro clínico comenzó con dolor en el hemitórax derecho y disnea, que se fue intensificando hasta el punto de no tolerar el decúbito. En la radiografía de tórax se observó colapso del pulmón derecho con múltiples bulas en ambos pulmones, por lo que se practicó una pleurotomía mínima alta derecha. La evolución del paciente no fue favorable por persistir el neumotórax, lo cual llevó al uso de un tratamiento alternativo. Discusión. En los pacientes con neumotórax persistente por enfisema bulloso bilateral sin indicación quirúrgica, el talco es una alternativa menos invasiva para lograr una sínfisis pleural con buenos resultados, método cuya utilidad se demuestra

Introduction. The aim of this report was to present the case of a patient with a history of bilateral bullous emphysema that causes a persistent pneumothorax that was difficult to treat. Clinical case. This is a 50-year-old patient diagnosed with pneumothorax associated with bilateral bullous emphysema, in whom surgical treatment being contraindicated. The clinical picture began with pain in the right hemithorax and dyspnea, which intensified to the point of not tolerating decubitus. In the chest X-ray, collapse of the right lung was observed with multiple bullae in both lungs, therefore a right upper minimum pleurotomy was performed. The patient's evolution was not favorable due to persisting pneumothorax, which led to the use of an alternative treatment. Discussion. In patients with persistent pneumothorax due to bilateral bullous emphysema without surgical indication, talc is a less invasive alternative to achieve a pleural symphysis with good results, a method whose utility is demonstrated

Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice.

Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-ß, tumor necrosis factor-α, neutrophils, IL-1ß, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.

Comment on "Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study".

In the clinical study by Le Thi Bich et al., allogeneic expanded umbilical cord-derived mesenchymal stem cells (UC-MSCs) were intravenously infused to treat patients with chronic obstructive pulmonary disease (COPD). No severe or significant adverse effects were observed, while a significant improvement in COPD patients' quality of life was reported up to 6 months. In addition, the authors argue that bone marrow-derived cells are not suitable to treat COPD based on the "failure" of 3 clinical trials (NCT01110252, NCT01306513, and NCT00683722). In fact, Le Thi Bich et al. and the three above-mentioned studies reported similar clinical outcomes, id est., no significant improvement in the pulmonary function of COPD patients. Therefore, since no COPD treatment involving cells either from bone marrow or umbilical cord was detrimental or provided lung regeneration in human patients, in our view, it is too early to point failures of cellular sources. Instead, it is a valuable opportunity to reflect on the poorly understood therapeutic mechanism of MSCs and the pathophysiology of COPD. In respect of cellular sources, only controlled trials with a strict comparison between different tissues might determine the suitability and efficacy of specific cell types to treat COPD. Finally, further studies are still required to determine whether and via which mechanism MSCs are able to provide structural and functional restoration of gas exchange in COPD patients.

Risk factors associated with the detection of pulmonary emphysema in older asymptomatic respiratory subjects.

BACKGROUND: Several lung structural and functional abnormalities may occur associated with aging, including emphysema. In this study, we evaluated the frequency and risk factors associated with emphysema in respiratory asymptomatic individuals enrolled in our Lung Aging Program. From a cohort of 687 subjects, we found by high-resolution computed tomography (HRCT) 29 individuals (4%) with emphysematous changes that were compared with 87 controls (3:1) randomly selected from the same cohort. METHODS: This was a transversal, observational, case-control study where we examined demographics and functional characteristics, as well as telomere length and serum Klotho concentration, two conditions that have been associated with aging and some aging-associated diseases including emphysema. RESULTS: Individuals with subclinical pulmonary emphysema were older (72 ± 9 versus 67 ± 6 years), and primarily smoker males with low body mass index. Despite that they were asymptomatic, two of them exhibited a decrease of forced expiratory volume in 1 s (FEV1), with a lower FEV1/FVC suggesting airway obstruction. Cigarette smoking (OR = 5.43, CI95% 1.8-16.7), family history of lung disease (OR = 4.32, CI95% 1.0-19.0) and lower body mass index (OR 7.22, CI95% 1.2-3.5) were risk factors for the development of lung emphysematous changes. No association was found with telomere length and Klotho serum concentration. CONCLUSION: Our findings reveal that a small but important percentage of older people without respiratory symptoms, present pulmonary emphysema and indicate that smoking exposure and genetic background may contribute to etiological factors.

Thinking in paracoccidioidomycosis: a delayed diagnosis of a neglected tropical disease, case report and review of clinical reports and eco-epidemiologic data from Colombia since the 2000.

BACKGROUND: Paracoccidioidomycosis is a neglected tropical disease, endemic in several countries of South America including Colombia. We report a case of a patient with Chronic Multifocal Paracoccidioidomycosis with long-standing symptoms and a delayed diagnosis caused by several barriers to achieve it. We did a review of the papers published in Colombia about this disease, focusing in clinical data and eco-epidemiology with the finding of a lack of new information on this topic since the 2000 in our region. CASE PRESENTATION: We present a 54-year-old man, farmer in his youth, with a chronic ulcerated lesion in the lower lip similar to a lip carcinoma, a deforming lesion in the nose, and respiratory symptoms with emphysematous lung. Lip biopsy with silver methenamine stain revealed small and large budding yeasts that resembles a "mariner's wheel" confirming Chronic Multifocal Paracoccidioidomycosis. He was treated successfully but subsequently lost to follow up. CONCLUSIONS: It is very important to focus attention, reinforce the search and create networks for the study of neglected tropical diseases. The presented case illustrates a usual clinical presentation, but with a delayed diagnosis due to the difficulties that still occur in some regions like ours for the early recognition of a case of chronic multifocal paracoccidioidomycosis.

Phytochemical study, molecular docking, genotoxicity and therapeutic efficacy of the aqueous extract of the stem bark of Ximenia americana L. in the treatment of experimental COPD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ximenia americana L. is popularly known as yellow plum, brave plum or tallow wood. All the parts of this plant are used in popular medicine. Its reddish and smooth bark are used to treat skin infections, inflammation of the mucous membranes and in the wound healing process. OBJECTIVE: Verification of phytochemical profile, the molecular interaction between flavonoid, (-) epi-catechin and 5-LOX enzyme, by means of in silico study, the genotoxic effect and to investigate the pharmacological action of the aqueous extract of the stem bark of X. americana in pulmonary alterations caused by experimental COPD in Rattus norvegicus. MATERIALS AND METHODS: The identification of secondary metabolites was carried out by TLC and HPLC chromatographic methods, molecular anchoring tests were applied to analyze the interaction of flavonoid present in the extract with the enzyme involved in pulmonary inflammation process and the genotoxic effect was assessed by comet assay and micronucleus test. For induction of COPD, male rats were distributed in seven groups. The control group was exposed only to ambient air and six were subjected to passive smoke inhalations for 20 min/day for 60 days. One of the groups exposed to cigarette smoke did not receive treatment. The others were treated by inhalation with beclomethasone dipropionate (400 mcg/kg) and aqueous and lyophilized extracts of X. americana (500 mg/kg) separately or in combination for a period of 15 days. The structural and inflammatory pulmonary alterations were evaluated by histological examination. Additional morphometric analyses were performed, including the alveolar diameter and the thickness of the right ventricle wall. RESULTS: The results showed that the aqueous extract of the bark of X. americana possesses (-) epi -catechin, in silico studies with 5-LOX indicate that the EpiC ligand showed better affinity parameters than the AracA ligand, which is in accordance with the results obtained in vivo studies. Genotoxity was not observed at the dose tested and the extract was able to stagnate the alveolar enlargement caused by the destruction of the interalveolar septa, attenuation of mucus production and decrease the presence of collagen fibers in the bronchi of animals submitted to cigarette smoke. CONCLUSION: Altogether, the results proved that the aqueous extract of X. americana presents itself as a new option of therapeutic approach in the treatment of COPD.

Pulmonary Hypertension in General Cardiology Practice / Hipertensão Pulmonar na Prática do Cardiologista

Abstract The finding of pulmonary hypertension (PH) by echocardiography is common and of concern. However, echocardiography is just a suggestive and non-diagnostic assessment of PH. When direct involvement of pulmonary circulation is suspected, invasive hemodynamic monitoring is recommended to establish the diagnosis. This assessent provides, in addition to the diagnostic confirmation, the correct identification of the vascular territory predominantly involved (arterial pulmonary or postcapillary). Treatment with specific medication for PH (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues) has been proven effective in patients with pulmonary arterial hypertension, but its use in patients with PH due to left heart disease can even be damaging. In this review, we discuss the diagnosis criteria, how etiological investigation should be carried out, the clinical classification and, finally, the therapeutic recommendations for PH.

Resumo O achado de hipertensão pulmonar (HP) em avaliação ecocardiográfica é frequente e preocupante. No entanto, o ecocardiograma é apenas um exame sugestivo e não diagnóstico de HP. Quando se suspeita de acometimento direto da circulação pulmonar, está indicada medida hemodinâmica invasiva para estabelecer o diagnóstico. Essa avaliação permite, além da confirmação diagnóstica, a correta identificação do território vascular predominantemente acometido (arterial pulmonar ou pós-capilar). O tratamento com as medicações específicas de HP (inibidores da fosfodiestarese 5, antagonistas do receptor de endotelina, análogos da prostaciclina e estimulador da guanilil ciclase solúvel) é comprovadamente eficaz para pacientes com hipertensão arterial pulmonar, mas seu uso em pacientes com HP decorrente de doença cardíaca de câmaras esquerdas pode até mesmo ser prejudicial. Discutiremos nesta revisão o critério diagnóstico, a maneira de proceder a investigação etiológica, a classificação clínica e, finalmente, as recomendações terapêuticas na HP.

Microenvironmental stimuli induce different macrophage polarizations in experimental models of emphysema.

Macrophages play a pivotal role in the development of emphysema and depending on the microenvironment stimuli can be polarized into M1- or M2-like macrophage phenotypes. We compared macrophage polarizations in cigarette smoke (CS)- and porcine pancreatic elastase (PPE)-induced emphysema models. C57BL/6 mice were subdivided into four experimental groups. In the PPE group, animals received an intranasal instillation of PPE (0.677 IU); in the saline group, animals received an intranasal instillation of saline (0.9%). Animals from both groups were euthanized on day 28. In the CS group, animals were exposed to CS for 30 min, twice a day, 5 days per week for 12 weeks. In the control group, animals received filtered air. We observed an increase in total macrophages for both experimental models. For M1-like macrophage markers, we observed an increase in TNF-α+ and IFN-γ+ cells, Cxcl-9 and Cxcl-10 expressions in PPE and CS groups. Only in the CS group, we detected an increased expression of IL-12b For M2-like macrophages markers we observed a down regulation in IL-10, IL-4, IL-13, Arg1 and Fizz1 and an increase of TGF-ß+ cells in the PPE group, while for the CS group there was an increase in TGF-ß+ cells and IL-10 expression. All exposure groups were compared to their respective controls. In summary, we demonstrated that CS- and PPE-induced models resulted in different microenvironmental stimuli. CS exposure induced an environmental stimulus related to M1- and M2-like macrophage phenotypes similar to previous results described in COPD patients, whereas the elastase-induced model provided an environmental stimulus related only to the M1 phenotype.

Resultados del tratamiento con pleurostomía en pacientes con neumotórax espontáneo / Outcomes of Pleurostomy Treatment in Patients with Spontaneous Pneumothorax

RESUMEN Introducción: La presencia de aire dentro de la cavidad pleural es definida como neumotórax. El tratamiento quirúrgico inicial es la pleurostomía, que puede acarrear complicaciones, relacionadas con varios factores, entre los cuales se encuentra el diámetro de la sonda intratorácica utilizada. Objetivo: Evaluar los resultados del tratamiento con pleurostomía en pacientes con neumotórax espontáneo en el Hospital Universitario Manuel Ascunce Domenech. Método: Se realizó un estudio descriptivo longitudinal retrospectivo desde septiembre de 2012 hasta septiembre de 2017. Se estudiaron 63 pacientes afectos de neumotórax espontáneos que recibieron pleurostomía como tratamiento inicial. Resultados: Los neumotórax espontáneos primarios representaron 56 por ciento de los casos. Del total de pacientes, 82 por ciento eran fumadores. En todos los pacientes el síntoma predominante fue el dolor. Las complicaciones fueron más frecuentes con el uso de sondas pleurales de menor diámetro (86 por ciento). Conclusiones: El neumotórax espontáneo primario fue el de mayor frecuencia. Las causas predominantes en el neumotórax secundario fueron las bulas de enfisema y la enfermedad pulmonar obstructiva crónica. En la totalidad de los casos, estuvo presente algunos de los síntomas del síndrome pleural con predominancia absoluta del dolor. El mayor número de complicaciones se presentó en pacientes fumadores(AU)

ABSTRACT Introduction: The presence of air within the pleural cavity is defined as pneumothorax. The initial surgical treatment is pleurostomy, which can lead to complications associated with several factors, among which is the diameter of the intrathoracic probe that is used. Objective: To evaluate the outcomes of the treatment with pleurostomy in patients with spontaneous pneumothorax at Manuel Ascunce Domenech University Hospital. Method: A retrospective, longitudinal, descriptive study was conducted from September 2012 to September 2017. We studied 63 patients affected by spontaneous pneumothorax who received pleurostomy as initial treatment. Results: Primary spontaneous pneumothorax accounted for 56 percent of the cases. From the total amount of patients, 82 percent were smokers. In all patients, the predominant symptom was pain. Complications were more frequent with the use of pleural probes of smaller diameter (86 percent). The primary spontaneous pneumothorax was the most frequent. The predominant causes of secondary pneumothorax were bullous emphysema and chronic obstructive pulmonary disease. In all the cases, some of the symptoms of pleural syndrome with absolute predominance of pain were present. The greatest number of complications occurred in smoking patients. Conclusions: Pleurostomy, with the use of the drainage catheter, is the initial treatment for all patients with spontaneous pneumothorax in our hospital, regardless of the diameter of the probe to be used according to the type of pneumothorax (primary or secondary)(AU)

Pneumostomia: uma proposta operatória para o tratamento do enfisema pulmonar difuso grave / Pneumostomy: an operative proposal for the treatment of severe diffuse pulmonary emphysema

RESUMO Objetivo: avaliar uma nova técnica operatória para o tratamento do enfisema pulmonar avançado. Métodos: análise prospectiva de nove pacientes portadores de enfisema pulmonar grave, submetidos à pneumostomia. O procedimento foi realizado sob anestesia local, na parede torácica anterior, linha hemiclavicular, no segundo espaço intercostal, através de toracotomia anterior de 5cm para acesso ao lobo superior, cujo segmento anterior foi pinçado e fixado à pleura parietal. Realizada pneumotomia com eletrocautério e inserção romba de dispositivo (dreno) intrapulmonar. Para avaliação do procedimento, foram realizados os seguintes exames: testes de função pulmonar, exames de imagens, teste da caminhada de seis minutos e questionários de qualidade de vida, medidos todos no pré-operatório e 30 dias após o procedimento. Resultados: não houve mortes relacionadas ao procedimento. Exames de imagens mostraram diminuição do volume pulmonar. A função pulmonar mostrou significante redução do volume residual. O teste de caminhada de seis minutos mostrou um aumento na distância percorrida no pós-operatório. Houve melhora significante da qualidade de vida, demonstrada por meio dos seguintes questionários: Medical Outcomes Study 36 Item Short - Form Health Survey (SF-36), Saint-George Respiratory Questionnaire (SGRQ), Medical Research Council scale (MRC) e Eastern Cooperative Oncology Group Performance status (ECOG). Conclusão: a técnica proposta é viável, segura, de fácil realização e manutenção.

ABSTRACT Objective: to evaluate a new operative technique for the treatment of advanced pulmonary emphysema. Methods: we conducted a prospective analysis of nine patients with severe pulmonary emphysema submitted to pneumostomy. The procedure was performed under local anesthesia, in the anterior thoracic wall, hemiclavicular line, in the second intercostal space, through an anterior thoracotomy of 5cm for access to the upper lobe, whose anterior segment was pinched and fixed to the parietal pleura. We carried out the pneumostomy with electrocautery and blunt insertion of an intrapulmonary drain. To assess the procedure, we performed pulmonary function tests, imaging tests, six-minute walk test, and applied quality of life questionnaires, all measured preoperatively and 30 days after the procedure. Results: no deaths occurred related to the procedure. Imaging studies showed a decrease in lung volume. The pulmonary function showed a significant reduction in the residual volume. The six-minute walk test showed an increase in the distance covered in the postoperative period. There was significant improvement of the quality of life as demonstrated through questionnaires Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36), Saint-George Respiratory Questionnaire (SGRQ), Medical Research Council scale (MRC), and Eastern Cooperative Oncology Group Performance status (ECOG). Conclusion: the proposed technique is feasible, safe, easy to perform and to maintain.

Eficacia de la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar de personas mayores con Enfermedad Pulmonar Obstructiva Crónica: revisión sistemática de literatura / Effectiveness of budesonide/formoterol compared to fluticasone / salmeterol in improving the lung capacity of older people with Chronic Obstructive Pulmonary Disease: systematic literature review / Eficiência da budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar de idosos com Doença Pulmonar Obstrutiva Crônica: revisão sistemática da literatura

Introducción. La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una patología no transmisible, caracterizada por una limitación de flujo de aire en las vías respiratorias debido a una respuesta inmunológica anormal frente a partículas. Objetivo. Conocer la eficacia que tiene la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar en personas mayores de 40 años con Enfermedad Pulmonar Obstructiva Crónica. Materiales y métodos. Se realizó una revisión sistemática de documentos producidos entre el año 2000 y 2018 en distintas bases de datos, donde se incluyeron ensayos clínicos. Se identificaron cuatro artículos para el análisis final. Resultados. Durante la evaluación comparativa de budesonida con formoterol, los artículos muestran un total de 709 personas evaluadas, con un promedio de edad de 53,5 años. El 65,4 % eran varones, el 21 % manifestaba no haber consumido tabaco, todos con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica moderada-severa, según la escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Los estudios determinaron que al administrar budesonida/formoterol de 400/12 mcg y 320/9 mcg, los pacientes tuvieron una leve mejoría en el Volumen Espiratorio Forzado del primer segundo (VEF1). Solo dos pacientes presentaron efectos adversos. No obstante, para los resultados mencionados anteriormente no se encontró diferencias significativas. Conclusiones. El uso de budesonida/formoterol es eficaz al mejorar la capacidad ventilatoria pulmonar, disminuye el número de exacerbaciones anuales y genera un adecuado control de los síntomas, sin embargo, es igual de efectivo a la fluticasona/salmeterol.

Introduction. Chronic Obstructive Pulmonary Disease (COPD) is a not transmissible disease, characterized by a limitation of airflow in the respiratory tract, due to an abnormal immune response to particles. Objective. This article aims to show that the application of budesonide / formoterol improves lung capacity in people over 40 years with Chronic Obstructive Pulmonary Disease. Materials and methods. A systematic review was conducted in the period between 2000 and 2018 in different databases where clinical trials were included. Four articles were identified for the final analysis. Results. During the comparative evaluation of budesonide with formoterol, a total of 709 people were evaluated, with an average age of 53.5 years, 65.4% were male, 21% reported not having used tobacco, all with a diagnosis of moderate-severe Chronic Obstructive Pulmonary Disease according to the GOLD scale (Global Initiative For Chronic Obstrutive Lung Disease). The studies determined that when budesonide / formoterol of 400/12 mcg and 320/9 mcg was administered, the patients had a slight improvement in the Forced Expiratory Volume of the first second (FEV1). Only two patients presented adverse effects. However, for the results mentioned above no significant differences were found. Conclusions. The use of budesonide / formoterol is effective in improving pulmonary ventilatory capacity, decreases the number of annual exacerbations and generates adequate control of symptoms, however, it is equally effective in fluticasone / salmeterol.

Introdução. A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma patologia não transmissível, caraterizada por uma limitação do fluxo de ar nas vias aéreas devido a uma resposta imune anormal contra partículas. Objetivo. Conhecer a eficiência que apresenta a budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar em pessoas com mais de 40 anos com Doença Pulmonar Obstrutiva Crônica. Materiais e métodos. Foi realizada uma revisão sistemática dos documentos produzidos entre 2000 e 2018 em diferentes bancos de dados, onde foram incluídos ensaios clínicos. Quatro artigos foram identificados para a análise final. Resultados. Durante a avaliação comparativa de budesonida com formoterol, os artículos mostram um total de 709 pessoas avaliadas, com uma idade média de 53,5 anos. O 65,4 % eram do sexo masculino, o 21 % disseram que não usavam tabaco, todos diagnosticados com Doença Pulmonar Obstrutiva Crônica moderada a grave, de acordo com a escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Os estudos determinaram que administrar budesonida/formoterol de 400/12 mcg e 320/9 mcg, os pacientes apresentaram uma leve melhora no Volume Expiratório Forçado no primeiro segundo (VEF1). Apenas dois pacientes tiveram efeitos adversos. No entanto, não foram encontradas diferenças significativas para os resultados mencionados acima. Conclusões. O uso de budesonida/formoterol é eficaz na melhora da capacidade ventilatória pulmonar, diminui o numero de exacerbações anuais e gera controle adequado dos sintomas, no entanto, é igualmente eficaz para a fluticasona/salmeterol.