COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages.

COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.

Use of fractional exhaled nitric oxide as a potential predictor of bronchodilator response.

Nitric oxide (NO) is an important product of eosinophilic metabolism, and its increase is associated with bronchial remodeling and airway hyperresponsiveness. Fractional exhaled NO (FENO) in the expired air of patients with suspected or diagnosed asthma has been used as a marker for eosinophilic inflammation. This cohort study included asthmatic patients classified under steps 3, 4, or 5 of the global strategy for asthma management and prevention. In the morning of the same day, all patients underwent blood collection for eosinophil counts, followed by FENO measurement and spirometry. We considered 2 groups based on the bronchodilation (BD) response on spirometry (>10% of FVC or FEV1): positive (BD+) and negative (BD-). Differences between the 2 groups were analyzed for demographic features, FENO values, and predictive correlations between FENO and BD. Both groups of patients showed an increase in the eosinophil count (BD+, P = .03; BD-, P = .04) and FENO values (P = .015 for both) with an increase in the asthma severity from step 3 to step 5 of the global strategy for asthma management and prevention. The correlations of FENO and eosinophils as well as FENO values and BD + were 0.127 (95% confidence interval,-0.269 to -0.486) and 0.696 (95% confidence interval, 0.246-0.899; P = .007), respectively. Measuring FENO levels may be useful for identifying patients with BD+.

Mortality and comorbidities in patients with bronchiectasis over a 3-year follow-up.

To identify the risk factors associated with all-cause mortality in patients with noncystic fibrosis bronchiectasis (NCFB). This prospective cohort study included 120 adult patients with NCFB, who were regularly treated at a specialized outpatient clinic of a university hospital between January 2017 and June 2020. All patients were diagnosed using high-resolution computed tomography. Demographic and clinical data, pulmonary function tests, and the Euro-quality-of-life 5-domain 3-level questionnaire were analyzed. The factors associated with death were determined using the Cox proportional hazards model. The all-cause mortality rate at 41 months was 10.8%. Adjusted multivariate analysis showed that the main contributing predictors for mortality were female sex, smoking, diabetes, chronic obstructive pulmonary disease, emergency visits, use of antibiotics due to exacerbation, secretion color change, exacerbation, predicted forced expiratory volume in 1 second, predicted forced vital capacity, lack of respiratory physiotherapy, absence of vaccination against pneumococci, and mobility domain. Multiple factors contribute to unfavorable outcomes in patients with NCFB, and early recognition of these factors may improve care management.

Acute Pulmonary Histoplasmosis Following COVID-19: Novel Laboratorial Methods Aiding Diagnosis.

The acute form of histoplasmosis usually occurs after the exposition of more than one individual to a common environmental source harboring Histoplasma capsulatum. Here, we present two cases of acute pulmonary histoplasmosis seen within two weeks at a reference center for infectious diseases at Rio de Janeiro, Brazil. The patients did not present a common epidemiologic history for histoplasmosis, however both presented COVID-19 before the onset of histoplasmosis symptoms. Due to the difficulties in the diagnosis of acute histoplasmosis, novel laboratory methods such as Western Blot and PCR were included in the investigation of these cases. Both patients presented negative cultures for H. capsulatum and negative urinary galactomannan. However, they presented H and M bands in the Western blot as well as a positive H. capsulatum DNA detection in sputum. These results were available approximately 36 h after sample collection, fastening the beginning of treatment of one patient. Both patients progressed well with itraconazole treatment. These cases suggest that COVID-19 may facilitate the development of acute pulmonary histoplasmosis and, therefore, clinicians must be aware of this differential diagnosis in patients from endemic areas with fever and coughing after recovery from COVID-19.

Evaluation Of HHIP Polymorphisms And Their Relationship With Chronic Obstructive Pulmonary Disease Phenotypes.

Purpose: We aimed to correlate three polymorphisms of the Hedgehog Interacting Protein (HHIP) gene with the three main phenotypes of the chronic obstructive pulmonary disease (frequent exacerbator (FE), asthma/COPD overlap (ACO), and emphysema with hyperinflation). Patients and methods: A cross-sectional study was carried out in the Department of Pulmonology at the Rio de Janeiro State University from February 2015 to July 2018. A total of 81 patients diagnosed with COPD according to the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were enrolled. The subjects were divided into three distinct groups according to their phenotypes (FE, ACO and emphysema-hyperinflation). Three polymorphisms of the HHIP gene that are often reported as allegedly involved in the pathogenesis of COPD were analysed: rs1828591, rs13118928, and rs6537296. Real-time PCR - TAQMAN SNP Genotyping Assay was performed. The statistical analysis was carried out with the SPSS program with a multivariate analysis with a 95% confidence interval. Results: An increase in the frequency of the A allele of the rs13118928 HHIP gene polymorphism was observed in the group of subjects with COPD and emphysema-hyperinflation phenotype when compared with those in the FE phenotype (p=0.019) and subjects with ACO (p=0.04). However, the subjects with emphysema-hyperinflation phenotype presented more often the A allele (p=0.04). The genotypic analysis confirmed the difference between the emphysema-hyperinflation and ACO phenotypes, with a higher prevalence of the AA genotype in the emphysema-hyperinflation group (p=0.04). The ACO and FE phenotype subjects showed no difference in these polymorphisms. No difference was found in the frequency of the polymorphisms rs1828591 (p= 0.552) and rs6537296 (p=0.296) in the three phenotypes evaluated. Conclusion: The presence of the A allele in the rs13118928 polymorphism of the HHIP gene may be related to the emphysema-hyperinflation phenotype.

Evaluation of von Willebrand factor in COPD patients.

OBJECTIVE: To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers. METHODS: The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9). During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic. RESULTS: Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01). Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05). In all three groups, there was a negative correlation between FEV1 (% of predicted) and relative serum vWF activity (r2 = -0.13; p = 0.009). CONCLUSIONS: Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.

Fenótipos da DPOC: há interesse prático nesta avaliação? / COPD phenotypes: Is it interesting in clinical practice?

A doença pulmonar obstrutiva crônica é causa importante de mortalidade no mundo e está presente em 90-95% dos indivíduos que se expõem ao tabagismo. Há muito tem se discutido a heterogeneidade da doença, inicialmente subdividindo a expressão clínica em dois grandes grupos: "Pink puffer" e "Blow blooter". Recentemente, tem sido descrito diferentes fenótipos da doença subdividindo os pacientes em diversos grupos. Destacam-se como mais prevalentes o exacerbador, a síndrome de sobreposição asma/DPOC e o enfisema com hiperinsuflação. Entretanto, será que devemos, em consulta clínica, estar preocupados em classificar o nosso paciente nestes subgrupos? Essa pergunta é foco de grande discussão, mas à luz dos conhecimentos atuais essa subdivisão parece ser interessante para fins de decisão e escalonamento terapêutico, individualizando o tratamento com o objetivo de maior efetividade terapêutica.

Chronic obstructive pulmonary disease is an important cause of and in 90-95% of cases is associated smoking habit. The heterogeneity of the disease has long been discussed dividing the clinical expression of the disease into two major groups: Pink puffer and Blow blooter. Recently, different phenotypes of the disease have been described, subdividing the patients into several groups. The following stand out: Exacerbator, overlap asthma / COPD syndrome, emphysema with hyperinflation and others. However, is important for us to classify our patients in these subgroups? This question is a focus of great discussion, but the light of current knowledge this subdivision seems to be interesting to decide about which drug we will choose to achieve individual effectiveness.

Hemophagocytic syndrome due to pulmonary sarcoidosis.

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.

[Usefulness of chest CT in the diagnosis of pulmonary sequestration]. / A utilidade da TC de tórax no diagnóstico do sequestro pulmonar.

Pulmonary sequestration is a rare congenital anomaly, characterized by nonfunctional embryonic pulmonary tissue. Pulmonary sequestration accounts for 0.15-6.40% of all congenital pulmonary malformations. This anomaly, which is classified as intralobar or extralobar, involves the lung parenchyma and its vascularization. We report the case of a 56-year-old male presenting with hemoptysis. A chest X-ray showed an area of opacity behind the cardiac silhouette in the base of the left hemithorax. Chest CT scans with intravenous contrast revealed pulmonary sequestration. The patient underwent surgery, in which the anomalous tissue was successful resected. The postoperative evolution was favorable, and the patient was discharged to outpatient treatment.

Evaluation of von Willebrand factor in COPD patients / Avaliação do fator de von Willebrand em pacientes com DPOC

OBJECTIVE: To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers. METHODS: The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9). During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic. RESULTS: Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01). Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05). In all three groups, there was a negative correlation between FEV1 (% of predicted) and relative serum vWF activity (r2 = −0.13; p = 0.009). CONCLUSIONS: Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients. .

OBJETIVO: Comparar os níveis séricos absolutos e a atividade sérica em percentual do fator de von Willebrand (FvW) em pacientes com DPOC clinicamente estáveis, tabagistas sem obstrução das vias aéreas e em indivíduos saudáveis que nunca fumaram. MÉTODOS: Foram incluídos no estudo 57 indivíduos, em três grupos: DPOC (n = 36), tabagista (n = 12) e controle (n = 9). Todos os participantes realizaram radiografia do tórax, espirometria e exame de sangue durante a fase de seleção. Os níveis séricos absolutos e a atividade sérica em percentual do FvW foram obtidos por turbidimetria e ELISA, respectivamente. A escala Medical Research Council modificada foi utilizada para classificar pacientes como sintomáticos ou assintomáticos/pouco sintomáticos no grupo DPOC (ponto de corte = 2). RESULTADOS: Os níveis absolutos do FvW no grupo controle foram significativamente menores que os nos grupos tabagista e DPOC: 989 ± 436 pg/mL vs. 2.220 ± 746 pg/mL (p < 0,001) e 1.865 ± 592 pg/mL (p < 0,01). Os valores em percentual de atividade do FvW no grupo DPOC foram significativamente maiores que no grupo tabagista (136,7 ± 46,0% vs. 92,8 ± 34,0%; p < 0,05), assim como foram significativamente maiores no subgrupo DPOC sintomático que no subgrupo DPOC assintomático/pouco sintomático (154 ± 48% vs. 119 ± 8%; p < 0,05). Houve uma correlação negativa entre o VEF1 (% do previsto) e os níveis em percentual de atividade do FvW nos três grupos (r2 = −0,13; p = 0,009). CONCLUSÕES: Nossos resultados sugerem que aumentos nos níveis de FvW e de sua atividade contribuem para a manutenção da inflamação sistêmica e o aumento do risco cardiovascular em pacientes com DPOC. .

Characteristic aspects of alveolar proteinosis diagnosis / Aspectos característicos do diagnóstico da proteinose alveolar

Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90 percent of the cases. In this case report we present a young male patient that was diagnosed with alveolar proteinosis. Computed tomography of the thorax, bronchoscopy and transbronchial biopsy were performed. The histopathologic aspect was characteristic. The patient was discharged in good health conditions and remains asymptomatic to date.

Proteinose alveolar é uma doença pulmonar incomum caracterizada pelo acúmulo de surfactante nas vias aéreas terminais e nos alvéolos, alterando a troca gasosa e, em alguns casos, promovendo insuficiência respiratória. Três formas clínicas e etiologicamente distintas de proteinose alveolar são reconhecidas: congênitas, secundárias e idiopáticas (mais de 90 por cento dos casos são de etiologia idiopática). Neste relato, apresentamos um homem jovem que foi diagnosticado com proteinose pulmonar. Tomografia computadorizada de tórax, broncoscopia e biópsia transbrônquica foram realizadas. O aspecto histopatológico foi característico. O paciente teve alta, com boas condições de saúde, e encontra-se assintomático nos dias de hoje.

Síndrome hemofagocítica devido a sarcoidose pulmonar / Hemophagocytic syndrome due to pulmonary sarcoidosis

Embora seja uma condição clínica rara, a síndrome hemofagocítica é associada com alta mortalidade e o número de casos descritos na literatura vem aumentando progressivamente. O diagnóstico de síndrome hemofagocítica depende da presença de hemofagocitose. A sarcoidose é uma doença de alta prevalência cujo curso e prognóstico podem correlacionar-se com a apresentação clínica inicial e a extensão da doença. Relatamos o caso de um paciente com sarcoidose de longa duração que apresentava febre intermitente e fadiga. O diagnóstico de síndrome hemofagocítica foi realizado por aspirado de medula óssea, e o tratamento específico foi ineficaz. Trata-se do terceiro caso de síndrome hemofagocítica relacionada a sarcoidose na literatura mundial e o primeiro na literatura latino-americana. Os três casos tiveram desfecho desfavorável.

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.

A utilidade da TC de tórax no diagnóstico do sequestro pulmonar / Usefulness of chest CT in the diagnosis of pulmonary sequestration

O sequestro pulmonar é uma rara anomalia congênita, caracterizada por tecido pulmonar embrionário não funcionante, perfazendo 0,15-6,40 por cento de todas as malformações pulmonares congênitas. Essa anomalia envolve o parênquima e a vascularização pulmonar, sendo classificado como intralobar ou extralobar. Neste relato, descrevemos o caso de um paciente de 56 anos com hemoptise e imagem hipotransparente retrocardíaca em base de hemitórax esquerdo na radiografia de tórax. Após a realização de TC com contraste endovenoso, foi evidenciada a presença de sequestro pulmonar. O paciente foi submetido à cirurgia para a retirada do tecido anômalo, que foi realizada com sucesso. Apresentou boa evolução pós-operatória e recebeu alta com acompanhamento ambulatorial.

Pulmonary sequestration is a rare congenital anomaly, characterized by nonfunctional embryonic pulmonary tissue. Pulmonary sequestration accounts for 0.15-6.40 percent of all congenital pulmonary malformations. This anomaly, which is classified as intralobar or extralobar, involves the lung parenchyma and its vascularization. We report the case of a 56-year-old male presenting with hemoptysis. A chest X-ray showed an area of opacity behind the cardiac silhouette in the base of the left hemithorax. Chest CT scans with intravenous contrast revealed pulmonary sequestration. The patient underwent surgery, in which the anomalous tissue was successful resected. The postoperative evolution was favorable, and the patient was discharged to outpatient treatment.

Recidiva de doença de Hodgkin em paciente HIV positivo / Relapse of Hodgkin´s disease HIV patient

A doença de Hodgkin em paciente HIV positivo é cinco a dez vezes mais comum e tem maior probabilidade de recidiva, se comparada à população com sorologia negativa. Os autores descrevem o caso de um paciente de 33 anos, HIV positivo, com derrame pleural volumoso, que teve de ser submetido à toracotomia com biópsia pleural para diagnóstico de recidiva de doença de Hodgkin. A recidiva ocorreu quatro anos após o início da doença, tendo se apresentado com um subtipo histológico diferente, por provável efeito da quimioterapia prévia.

Tuberculose em paciente HIV positivo: sempre um desafio / Tuberculosis in HIV positive patient: always a challenge

A tuberculose tem incidência mundial estimada em torno de seis a oito milhões de casos novos por ano, sendo 50% destes na sua forma pulmonar. A infecção pelo vírus da imunodeficiência humana (HIV) foi um dos responsáveis pelo ressurgimento da epidemia de tuberculose no mundo.1 A coinfecção tuberculose e HIV aumentam o risco do indivíduo desenvolver apresentações atípicas e formas mais graves da doença,2 principalmente em pacientes com contagem de linfócitos CD4 abaixo de duzentas células/mm3.3 Os autores relatam o caso de um paciente soropositivo para HIV que abandonouo acompanhamento ambulatorial, há um ano, interrompendo o uso dos medicamentos antirretrovirais, sendo internado para investigação de febre e diarréia. Houve remissão do quadro diarréico após uso de nitazoxanida para tratamento de giardíase, mas a febre persistiu e a evolução clínico-radiológica levou ao diagnóstico de tuberculose pulmonar. O paciente apresentou disfunção miocárdica, com rápida melhora do quadro com dobutamina. Após um mês e meio de esquema terapêutico com rifampicina, isoniazida, pirazinamida e etambutol (RIPE), o paciente recebeu alta hospitalar com remissão da febre e em bom estado geral.

The incidence of tuberculosis in the world is estimated in six to eight millions cases per year, 50% of which have pulmonary tuberculosis. The HIV infection has contributed for resurgence of epidemic tuberculosis. When there is coinfection of HIV and tuberculosis atypical and severe forms of pulmonary tuberculosis are diagnosed mainly if CD4 lymphocytes count is below200cells/mm3. In this article, the authors report a patient that abandoned both clinical follow up and antiretroviral therapy by one year. He complained of fever and diarrhea. During the admission the diarrhea remitted after treatment for giardiasis withnitazoxanide, but the fever persisted daily. Pulmonary tuberculosis was diagnosed by clinical and radiographic evolution. Treatment with isoniazid, rifampin, pyrazinamide and ethambutol was initiated but there was myocardial disfunction that disappeared in few days with the use of dobutamine. After one month and half of treatment the fever disappeared and the patient was discharged.

CIV Pós-IM de parede inferior com ótima evolução pós-operatória: apresentação incomum de uma complicação cada vez menos frequênte / Ventricular septal rupture after inferior wall myocardial infarction with an excellent outcome after cardiac surgery: an uncommon presentation of a less and less frequent complication

Apesar de comumente citada como complicação mecânica do infarto agudo do miocárdio, a comunicação interventricular (CIV) ocorre com frequência cada vez menor após o advento da terapia trombolítica. Neste relato, os autores descrevem o caso de um homem de 54 anos com CIV após 8 dias de infarto de parede inferior, com características clínicas, eletrocardiográficas e ecocardiográficas peculiares e uma ótima evolução após cirúrgia cardíaca.

Despite being commonly referred to as a mechanical complication of acute myocardial infarction, ventricular septal rupture (VSR) has occurred less andless frequently since the breakthrough ofthrombolytic therapy. In this case report, the authors describe a 65-year-old man with a VSR 8 days after an inferior wall infarction, with particular clinical, electrocardiographic, and echocardiographic features and an excellent outcome after cardiac surgery.