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BACKGROUND AND OBJECTIVE: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH. METHODS: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline-pyrrole (MCT-P) in wild-type (WT) and periostin-/- mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)-2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH-induced WT and periostin-/- mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated. RESULTS: In PH induced by SuHx and MCT-P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin-/- mice. PA remodelling post-SuHx treatment was also mild in periostin-/- mice compared to WT mice. Expression of macrophage-associated chemokines and FGF-2 in lung tissue, and accumulation of CD68-positive cells in the RV were less in SuHx periostin-/- than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor-ß. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls. CONCLUSION: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH.
Assuntos
Moléculas de Adesão Celular , Fator 2 de Crescimento de Fibroblastos , Hipertensão Pulmonar , Macrófagos , Animais , Moléculas de Adesão Celular/genética , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Artéria Pulmonar/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: Recent imaging studies demonstrated the usefulness of quantitative computed tomographic (CT) analysis assessing pulmonary hypertension (PH) in patients with chronic obstructive lung disease (COPD-PH). The aim of this study was to investigate whether it would be also valuable for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH. METHODS: We analyzed a correlation between the extent of cystic destruction (LAA%) and total cross-sectional areas of small pulmonary vessels less than 5 mm(2) (%CSA <5) in many CT slices from each of four COPD-PH patients before and after the initiation of pulmonary vasodilator. To evaluate those generalized data from patients with COPD, we evaluated multiple slices from 42 patients whose PH was not clinically suspicious. We also selected five PH patients with idiopathic interstitial pneumonia (IIP-PH) and analyzed serial changes of pulmonary artery enlargement (PA:A ratio). RESULTS: In 42 COPD patients without PH, LAA% had a statistically significant negative correlation with %CSA <5. However, three of four COPD-PH patients manifested no such correlation. In two patients, clinical findings were dramatically improved after the initiation of pulmonary vasodilator. Notably, LAA% and %CSA <5 in those patients correlated significantly after its treatment. In COPD-PH, the PA:A ratio was significantly decreased after the initiation of pulmonary vasodilator therapy (1.25 ± 0.13 vs. 1.13 ± 0.11, p = 0.019), but not in IIP-PH. CONCLUSIONS: Our study demonstrates that the use of quantitative CT analysis is a plausible and beneficial tool for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH.
Assuntos
Hipertensão Pulmonar/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Bosentana , Antagonistas dos Receptores de Endotelina/uso terapêutico , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Citrato de Sildenafila/uso terapêutico , Sulfonamidas/uso terapêutico , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios X , Vasodilatadores/uso terapêutico , Capacidade VitalRESUMO
BACKGROUND: The prognosis of pulmonary hypertension (PH) associated with connective tissue diseases related to interstitial pneumonia (CTD-IP PH) is relatively good among patients with PH and lung disease. However, the impact of pulmonary vasodilator treatment on the prognosis of CTD-IP PH compared with that of PH-induced chronic lung disease (group-3 PH) remains unclear. METHODS: From 2012 to 2022, 50 patients with lung parenchymal lesions diagnosed with PH (mean pulmonary arterial pressure >20 mmHg) at Juntendo University Hospital were divided into two groups: CTD-IP PH (30 patients) and group 3-PH (20 patients). The impact of pulmonary vasodilator treatment and the use of long-term oxygen therapy (LTOT) on the prognosis of each group was examined retrospectively. RESULTS: The prognosis of CTD-IP PH was significantly better compared to group-3 PH. While the treatment with pulmonary vasodilators did not affect the prognosis in group 3-PH, the prognosis of the patients treated with vasodilators in the CTD-IP PH group was significantly better than that of the non-treated patients. Treatment with multi-pulmonary vasodilators did not affect the prognosis in CTD-IP PH. Although the prognosis for the patients with LTOT was poor in all registered patients in the present study, treatment with pulmonary vasodilators improved the prognosis even under the use of LTOT in CTD-IP PH (P = 0.002). In a multivariate analysis of the CTD-IP PH group, pulmonary vasodilator treatment was an independent factor for better prognosis. CONCLUSION: Treatment with a pulmonary vasodilator for CTD-IP PH may improve the prognosis, even in patients requiring LTOT.
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Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Humanos , Prognóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Estudos Retrospectivos , Pulmão , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Vasodilatadores/uso terapêuticoRESUMO
Objective Based on the increasing incidence of smell and taste dysfunction among coronavirus disease 2019 (COVID-19) patients, such issues have been considered an early symptom of infection. However, few studies have investigated the type of taste components that are most frequently affected in COVID-19 patients. This study investigated the difference in frequencies of the types of taste component disorders among hospitalized COVID-19 patients. Methods In this retrospective, single-center, observational study, patients' background characteristics, clinical course, laboratory and radiological findings, and details on taste and/or smell disorders were collected and analyzed from medical records. Patients A total of 227 COVID-19 patients were enrolled, among whom 92 (40.5%) complained of taste disorders. Results Multiple types of taste disorders (hypogeusia/ageusia and hypersensitivity, or hypersensitivity and changing tastes) were reported in 10 patients. In particular, 23 patients reported hypersensitivity to at least 1 type of taste, and 2 patients complained of a bitter taste on consuming sweet foods. Impairment of all taste components was found in 48 patients (52.2%). The most frequent taste disorder was salty taste disorder (81 patients, 89.0%). Hypersensitivity to salty taste was most frequently observed (19 patients, 20.9%). Conclusion Patients with COVID-19 develop multiple types of taste disorders, among which salty taste disorder was the most frequent, with many patients developing hypersensitivity to salty taste. As smell and taste are subjective senses, further studies with the combined use of objective examinations will be required to confirm the findings.
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Ageusia , COVID-19 , Ageusia/epidemiologia , Ageusia/etiologia , COVID-19/complicações , Disgeusia/complicações , Disgeusia/etiologia , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Paladar , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologiaRESUMO
Neointimal lesion and medial wall thickness of pulmonary arteries (PAs) are common pathological findings in pulmonary arterial hypertension (PAH). Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling contribute to intimal and medial vascular remodeling in PAH. Nintedanib is a tyrosine kinase inhibitor whose targets include PDGF and FGF receptors. Although the beneficial effects of nintedanib were demonstrated for human idiopathic pulmonary fibrosis, its efficacy for PAH is still unclear. Thus, we hypothesized that nintedanib is a novel treatment for PAH to inhibit the progression of vascular remodeling in PAs. We evaluated the inhibitory effects of nintedanib both in endothelial mesenchymal transition (EndMT)-induced human pulmonary microvascular endothelial cells (HPMVECs) and human pulmonary arterial smooth muscle cells (HPASMCs) stimulated by growth factors. We also tested the effect of chronic nintedanib administration on a PAH rat model induced by Sugen5416 (a VEGF receptor inhibitor) combined with chronic hypoxia. Nintedanib was administered from weeks 3 to 5 after Sugen5416 injection, and we evaluated pulmonary hemodynamics and PAs pathology. Nintedanib attenuated the expression of mesenchymal markers in EndMT-induced HPMVECs and HPASMCs proliferation. Phosphorylation of PDGF and FGF receptors was augmented in both intimal and medial lesions of PAs. Nintedanib blocked these phosphorylation, improved hemodynamics and reduced vascular remodeling involving neointimal lesions and medial wall thickening in PAs. Additionally, expressions Twist1, transcription factors associated with EndMT, in lung tissue was significantly reduced by nintedanib. These results suggest that nintedanib may be a novel treatment for PAH with anti-vascular remodeling effects.
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Proliferação de Células/efeitos dos fármacos , Células Endoteliais , Hipertensão Pulmonar , Indóis/farmacologia , Músculo Liso Vascular , Músculo Liso , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células HEK293 , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Ratos , Remodelação Vascular/efeitos dos fármacosRESUMO
BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the current major modality for the diagnosis of sarcoidosis with hilar and mediastinal lymphadenopathy because of its higher diagnostic yield and safety; however, predictors for the pathological diagnosis of sarcoidosis by EBUS-TBNA remain uncertain. The objective of this study was to determine a novel predictor for the pathological diagnosis of sarcoidosis by EBUS-TBNA. METHODS: Patients with pathological and/or clinical diagnosis of sarcoidosis were identified from patients who underwent EBUS-TBNA between February 2010 and December 2017, retrospectively. We extracted data on age, sex, stage of disease, number of punctured lymph nodes, number of punctures per procedure and target lymph node, and size of punctured lymph node. Next, we divided patients into groups of pathological positive and negative by EBUS-TBNA, and multivariate logistic regression analysis was performed following univariate analyses to evaluate the efficacy of these parameters as a predictive factor of the pathological diagnosis of sarcoidosis by EBUS-TBNA. RESULTS: We selected 89 patients involving 115 mediastinal and hilar lymph nodes. The diagnostic yield of sarcoidosis by EBUS-TBNA was 74/89 (83.1%). There were no significant differences in the size of lymph node and number of punctures between the groups, there was a significant difference in age by univariate analyses. In addition, multivariate logistic regression revealed that age was significantly associated with pathological diagnosis of sarcoidosis by EBUS-TBNA [5 years = 1 unit, odds ratio (OR), 0.79; 95% CI, 0.64-0.97; P=0.03]. CONCLUSIONS: The diagnostic yield of sarcoidosis by EBUS-TBNA was higher in younger than older patients. Therefore, age may be a novel independent predictor for the pathological diagnosis of sarcoidosis by EBUS-TBNA.
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A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings. The patient was diagnosed as having IVLBCL with pulmonary involvement based on a pathological analysis of a random skin biopsy and a transbronchial lung biopsy. IVLBCL should be considered in patients with symptoms of asthma that are refractory to corticosteroid treatment.
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Asma/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Humanos , Lactato Desidrogenases/sangue , Pulmão/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Receptores de Interleucina-2/sangue , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIM OF THE WORK: Decrease in renal function was investigated in relation to altered metabolism of calcium in patients with sarcoidosis. METHODS: Fifty consecutive patients with pulmonary sarcoidosis (23 men and 27 women, 47 +/- 15 years as mean +/- SD) were studied on a daily diet consisting of 500 mg of calcium and 1000 mg of phosphorus. Renal functions were evaluated with Z scores of creatinine clearance (Ccr). RESULTS: Decreased renal function (Ccr Z score < -1) was detected in 13 out of 50 sarcoidosis patients (26.0%). In seven patients (14.0%) Ccr Z scores were less than -2; relative risk (RR) and 95% confidence interval (95% CI) were 13.9 and 2.97 to 64.7, respectively. Ccr Z score correlated most significantly with serum concentration of ionized calcium (sCa2+) (r = -0.574, 95% CI, -0.735 to -0.352, p < 0.0001). A stepwise regression analysis adjusting for observation time, serum concentration of calcium and 1,25-Dihydroxyvitamin D, urinary excretion of calcium, and urinary calcium crystals showed that sCa2+, together with angiotensin-converting enzyme activity in serum, was the most contributory variable to decrease in renal function in sarcoidosis patients (R2 = 0.391, p < 0.0001). A cutoff value of sCa2, 1.30 mmol/L obtained with a discriminant analysis showed 69.2% of sensitivity and 89.2% of specificity for decreased renal function. CONCLUSIONS: We reported increased prevalence of decreased renal function among sarcoidosis patients. sCa2+ was a significant index that reflected the alteration of renal function.
Assuntos
Cálcio/sangue , Rim/fisiopatologia , Sarcoidose Pulmonar/fisiopatologia , Calcitriol/sangue , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Sarcoidose Pulmonar/sangue , Sensibilidade e EspecificidadeRESUMO
A 56-year-old woman was admitted to our hospital because a chest X-ray and thoracic computed tomography (CT) scan revealed a heterogeneous tumor in the middle mediastinum during a visit to a nearby clinic for a consultation regarding a persistent cough and body weight loss. However, the tumor spontaneously decreased on thoracic CT performed on admission. Subsequently, a biopsy of the tumor using video-assisted thoracoscopy was performed. The pathological findings disclosed the tumor to be small-cell lung cancer with infiltration of CD8-positive T-cells exhibiting spontaneous regression. Cell-mediated immunity, including CD8-positive T-cells, may have relevance to the spontaneous regression of malignant tumors.
Assuntos
Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Remissão Espontânea , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
BACKGROUND: The role of bronchoalveolar lavage fluid (BALF) cell profiles in predicting the clinical outcome of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is still under discussion. OBJECTIVE: To determine whether BALF cell profiles affect the survival of patients with UIP diagnosed by surgical lung biopsy/autopsy at the early stage of IPF. METHODS: This hospital-based retrospective cohort study used 81 Japanese patients with histologically proven IPF/UIP who underwent BAL examination. The BALF samples were obtained from non-current smokers: NCS (n = 41) and current smokers: CS (n = 40). The Kaplan-Meier and Cox's proportional hazard methods were used to estimate the survival and evaluate the risk ratio for death in the two groups. To detect the multicollinearity, a stepwise regression was employed. RESULTS: A slight increase in the absolute numbers of BALF neutrophils tended to relate to a decrease in the relative risk for death in NCS patients and CS patients in the univariate analysis. In stepwise regression, the increase in percent vital capacity and the increase in the BALF CD4/CD8 ratio in NCS was detected as a favorable predictor, while increased BALF cells affected the results due to chronic smoking in CS. CONCLUSIONS: Based on the study bias of the biopsy-proven IPF/UIP patients at stable stages, an independent variable indicating a favorable outcome was an increased BALF CD4/CD8 ratio in NCS patients, while it was difficult to identify definite prognosticators in CS patients.