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1.
Cell Immunol ; 393-394: 104769, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37741001

RESUMO

Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, ß1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.


Assuntos
Células Endoteliais , Pneumopatias , Humanos , Células Endoteliais/metabolismo , Leucócitos Mononucleares , Adesividade , Endotélio Vascular/metabolismo , Células Cultivadas , Citocinas/metabolismo , Pulmão , Receptor de Asialoglicoproteína/metabolismo
2.
Circ J ; 85(4): 333-342, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33536399

RESUMO

BACKGROUND: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. CONCLUSIONS: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Transtornos Respiratórios , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Japão , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Estudos Prospectivos , Transtornos Respiratórios/complicações , Transtornos Respiratórios/tratamento farmacológico
3.
Respiration ; 99(11): 961-969, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264771

RESUMO

BACKGROUND: There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). OBJECTIVES: To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. METHODS: Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). RESULTS: Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7-2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (p = 0.029). CONCLUSIONS: High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.


Assuntos
Bronquiectasia/terapia , Embolização Terapêutica , Hemoptise/terapia , Brônquios/diagnóstico por imagem , Artérias Brônquicas/diagnóstico por imagem , Artérias Brônquicas/microbiologia , Bronquiectasia/complicações , Bronquiectasia/microbiologia , Angiografia por Tomografia Computadorizada , Hemoptise/etiologia , Humanos , Estimativa de Kaplan-Meier , Recidiva , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento
4.
Lung ; 193(6): 911-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26453478

RESUMO

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 Vital
5.
Am J Physiol Lung Cell Mol Physiol ; 306(11): L996-L1005, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24705719

RESUMO

Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system.


Assuntos
Anti-Hipertensivos/farmacologia , Eritropoetina/biossíntese , Genisteína/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/fisiologia , Animais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipóxia Celular , GMP Cíclico/metabolismo , Avaliação Pré-Clínica de Medicamentos , Eritropoetina/fisiologia , Genisteína/uso terapêutico , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Vasodilatadores/farmacologia , Pressão Ventricular
6.
JACC Asia ; 4(5): 403-417, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38765657

RESUMO

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).

7.
Intern Med ; 62(12): 1743-1748, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36351578

RESUMO

Objective The incidence of tuberculosis in Japan has been decreasing in the overall population but is increasing in older patients ≥90 years old. A poor performance status due to underlying diseases makes it difficult for patients with tuberculosis to receive standard oral treatment. However, there is no consensus concerning alternative treatments. This study examined the treatments and outcomes of older patients with tuberculosis and a poor performance status and determined the limitations of tuberculosis treatment for them. Methods We retrospectively enrolled 121 older patients with tuberculosis and a performance status of 3 or 4 due to underlying diseases during their hospitalization between April 2015 and March 2017 at National Hospital Organization Tokyo National Hospital. We classified them according to the drug administration route (oral, enteral, and injection routes) on admission and compared the characteristics and prognoses among the three groups. Results There were 79 patients in the oral route group, 28 (35.4%) of whom died during hospitalization. Among the 15 patients in the enteral route group, 6 (40.0%) died. Among the 27 patients in the injection route group who received non-oral agents, 22 (81.5%) died. The prognosis of the injection route group was poor, with a median survival time of 21 days. Conclusion Treatment success cannot be expected with injection treatment in patients with a poor general condition because of complications. Although injection treatment may be a viable alternative treatment, its establishment as the standard treatment cannot be currently endorsed.


Assuntos
Tuberculose , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Prognóstico , Hospitalização , Japão/epidemiologia
8.
Microbiol Spectr ; 11(1): e0343522, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36475776

RESUMO

When Aspergillus, an ubiquitous, saprophytic fungus, is detected in respiratory tract specimens collected from chronic respiratory disease patients, it is important to determine whether it is a true infection or colonization. We investigated the usefulness of the Bio-Rad Platelia Aspergillus IgG (Platelia Aspergillus IgG) enzyme-linked immunosorbent assay (ELISA) method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Between January 2017 and November 2021, 51 confirmed, untreated pulmonary aspergillosis (33 chronic pulmonary aspergillosis [CPA] and 18 allergic bronchopulmonary aspergillosis [ABPA]) and 77 colonization patients were included in this study. At first, the conventional cutoff value was utilized in assessing the validity of the two antibody tests for distinguishing pulmonary aspergillosis from colonization. The Platelia Aspergillus IgG cutoff value was then reevaluated to fit this situation. Finally, differences in test accuracy dependent on Aspergillus species were assessed for both antibody tests by comparing cases with Aspergillus fumigatus complex and those with non-fumigatus Aspergillus complex. Both antibody tests demonstrated significantly higher positive rates for pulmonary aspergillosis (P < 0.0001) than colonization. The cutoff value should be 15.7 arbitrary units (AU)/mL to best distinguish infection from colonization, which was higher than the conventional value of 10 AU/mL. The diagnostic sensitivity of Platelia Aspergillus IgG for the non-fumigatus Aspergillus complex was inferior to the A. fumigatus complex (P = 0.019). In conclusion, both Aspergillus antibody tests were valid to distinguish infection from colonization, although we should note the higher cutoff value for Platelia Aspergillus IgG and the lower sensitivity in cases of non-fumigatus Aspergillus infection. IMPORTANCE Pulmonary aspergillosis is the most common pulmonary fungal infection. However, Aspergillus is a ubiquitous, saprophytic fungus; it can be detected in respiratory specimens even in the absence of infection. Especially since Aspergillus is detected in respiratory specimens collected from patients with chronic respiratory disease, it is important to determine whether it is true infection or colonization. We investigated the validity of the Platelia Aspergillus IgG ELISA method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Both antibody tests were considered useful in differentiating true infection from colonization in respiratory practice. The appropriate cutoff value for Platelia Aspergillus IgG was higher than the conventional value, and it was also noted that the sensitivity of both antibody tests for non-fumigatus Aspergillus complex was low. This study will be significant in real-world clinical practice of pulmonary aspergillosis using antibody tests in respiratory care.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergilose Pulmonar , Humanos , Testes de Precipitina , Aspergillus , Aspergilose Pulmonar/diagnóstico , Aspergilose Broncopulmonar Alérgica/diagnóstico , Anticorpos Antifúngicos/análise , Imunoglobulina G/análise , Aspergillus fumigatus
9.
Chest ; 164(1): e9-e13, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37423707

RESUMO

CASE PRESENTATION: A 65-year-old man experienced a cough and mild hemoptysis suddenly one morning. He was prescribed tranexamic acid and carbazochrome salicylate by the local clinic at the first visit, and his hemoptysis stopped. However, 2 days later, he experienced recurrent hemoptysis that was prolonged intermittently. He had slight dyspnea and chest discomfort, but no other symptoms, such as sputum, fever, or chest pain. He was referred to our hospital for further assessment of hemoptysis. He had experienced mild hemoptysis of unknown causes 8 years earlier without recurrence until this episode. He had bronchial asthma that was treated with an inhaled corticosteroid and hypertension and hyperuricemia that were untreated with medication. He had no known allergies or family history of lung disease. He did not smoke. The patient denied alcohol consumption, any recent travel, or exposure to TB.


Assuntos
Hemoptise , Pneumopatias , Masculino , Humanos , Idoso , Hemoptise/diagnóstico , Hemoptise/etiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Dispneia/etiologia , Pneumopatias/diagnóstico , Tosse/diagnóstico , Diagnóstico Diferencial
10.
Intern Med ; 59(24): 3201-3205, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32788540

RESUMO

Molecular-targeted drugs (MTDs), such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase inhibitors, are used to treat non-small-cell lung cancer (NSCLC). The incidence of rash caused by EGFR-TKIs and discontinuation of MTDs because of rash are issues. Rapid desensitization therapy (RDT) was performed in five patients who developed severe rash after introduction of MTDs and was successful in four, all of whom showed no rash relapse. RDT may thus be useful for treating rash in patients receiving MTDs for NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Exantema , Neoplasias Pulmonares , Preparações Farmacêuticas , Quinase do Linfoma Anaplásico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/efeitos adversos
11.
Respir Med Case Rep ; 29: 101003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32257787

RESUMO

Ovarian cancer is a critically lethal gynecologic malignancy. More than 80% of patients with ovarian cancer have relapses within 5 years after initial treatment. However, recurrence from ovarian cancer more than 20 years later is extremely rare. We report a case of a 67-year-old female with mediastinal metastasis from ovarian cancer 29 years after initial gynecologic surgery and chemotherapy.

12.
Pathol Int ; 59(10): 752-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19788622

RESUMO

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles in patients with metastatic carcinoma. Osteopontin (OPN) is a multifunctional cytokine and adhesive protein, and has been demonstrated to be implicated in fibrosis, neointima formation, arterial occlusion by thrombus, and tumor metastases in cooperation with platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Herein is described an autopsy case of gastric adenocarcinoma with severe pulmonary hypertension due to PTTM. Histologically, tumor cell emboli markedly induced both fibromuscular intimal thickening and thrombosis, resulting in luminal stenosis and occlusion of small pulmonary arteries and arterioles. Tumor cells, both in the PTTM lesions and primary gastric carcinoma, had positive immunoreactivity for OPN, PDGF, and VEGF. In addition, proliferating fibromuscular intimal cells also showed expression of OPN, PDGF, and VEGF. These findings suggest that OPN may be involved in fibrocellular intimal proliferation and thrombus formation in PTTM together with PDGF and VEGF. To the best of the authors' knowledge this is the first report to demonstrate the possible involvement of OPN in PTTM. It is postulated that OPN is one of the candidate molecules for the development of PTTM.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/metabolismo , Osteopontina/metabolismo , Neoplasias Gástricas/patologia , Microangiopatias Trombóticas/metabolismo , Adenocarcinoma/secundário , Adulto , Proliferação de Células , Evolução Fatal , Humanos , Hipertensão Pulmonar/etiologia , Neoplasias Pulmonares/secundário , Masculino , Fator de Crescimento Derivado de Plaquetas/metabolismo , Trombose/etiologia , Túnica Íntima/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Respir Med Case Rep ; 28: 100940, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31667076

RESUMO

Combined pulmonary fibrosis and emphysema (CPFE) is a common but under-recognized syndrome characterized with distinct profiles of both pulmonary fibrosis and emphysema. Pulmonary hypertension (PH) is particularly prone to develop as a common complication, leading to exercise limitation and worse prognosis of CPFE. Although the therapy of patients with PH from CPFE cannot be endorsed, an individual treatment may be considerable when accompanying severe PH. We report a case of a 71-year-old male with PH from CPFE, who improved pulmonary arterial compliance (PAC) and exercise capacity in response to pulmonary vasodilator.

14.
Respir Physiol Neurobiol ; 262: 20-25, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30660859

RESUMO

Pulmonary hypertension (PH) due to lung diseases is classified as group 3 by the Dana Point classification. Given the basic pathophysiological conditions of group 3 lung diseases and the previously well-known concept of hypercapnic pulmonary vasoconstriction, chronic hypercapnia besides alveolar hypoxia might be another causative factor to increase mean pulmonary arterial pressure (PAm). Two hundred twenty-five subjects with chronic pulmonary diseases were assessed by a right heart catheterization and blood gas parameters. The subjects were classified into the following 4 groups: Hypercapnic Hypoxia (HCHX), Hypercapnic Normoxia (HCnx), Normocapnic Hypoxia (ncHX), and Normocapnic Normoxia (ncnx). Compared with ncnx, the HCHX, HCnx and ncHX groups all showed significantly higher PAm and met the criteria of borderline PH. Multiple regression analysis showed that PaCO2, as well as SaO2, was an independent variable for PAm. Given the poor prognosis with borderline PH, the elimination of excess pulmonary carbon dioxide in hypercapnia could be a considerable treatment strategy in chronic pulmonary disease.


Assuntos
Hipercapnia/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Arterial , Gasometria , Doença Crônica , Feminino , Humanos , Hidrocarbonetos Clorados/metabolismo , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Estudos Retrospectivos , Adulto Jovem
15.
PLoS One ; 14(7): e0214697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339889

RESUMO

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.


Assuntos
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 fármacos
16.
Respirology ; 13(6): 913-5, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18657065

RESUMO

This report describes a case of isolated congenital spleen agenesis complicated by chronic thromboembolic pulmonary hypertension (CTPH) in a 44-year-old female patient. The patient had increasing exertional dyspnoea and thrombocytosis. An echocardiogram showed severe pulmonary hypertension and right ventricular hypertrophy, and contrast-enhanced chest CT revealed multiple thromboemboli within both pulmonary arteries. A perfusion lung scan demonstrated multiple segmental defects and no spleen was detected by abdominal CT, ultrasonography or scintigraphy. Comprehensive clinical examinations disclosed no evidence of a thrombus elsewhere or of an associated malformation such as a cardiac anomaly. Anticoagulation therapy was started, and a perfusion lung scan revealed partial improvement of the hypoperfusion in the right lower lobe. However, repeat echocardiography showed the pulmonary hypertension persisting for 1 year. The multiple segmental defects in the perfusion lung scans were also persistent. Collectively, a diagnosis of CTPH with isolated congenital spleen agenesis was established. This is the first documented case of CTPH in an adult with isolated congenital asplenia. Although congenital spleen agenesis is a rare condition, this case report suggests that this possibility should be considered when a diagnosis of CTPH and thrombocytosis is made.


Assuntos
Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Baço/anormalidades , Adulto , Dispneia/etiologia , Feminino , Humanos , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Trombocitose/etiologia , Tomografia Computadorizada por Raios X
17.
Respiration ; 75(3): 328-38, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18073453

RESUMO

BACKGROUND: Angiopoietins, newly discovered vascular-specific growth factors, and vascular endothelial growth factors (VEGF) play distinct and complementary roles in angiogenesis and vascular maturation. However, the exact roles of angiogenic factors in the adult pulmonary vasculature remain unclear. OBJECTIVE: To elucidate possible roles of angiopoietins and VEGF in the development of hypoxic pulmonary hypertension (PH), changes in the expression of angiogenic factors were examined. METHODS: The cellular distribution and expression of angiopoietins and their receptor Tie2 and VEGF were investigated by RT-PCR, immunoblot, and immunohistochemical methods in rat lung under normal and hypoxic conditions. RESULTS: During the development of PH with vascular remodeling characterized by a decrease in vessel density of intrapulmonary arteries, protein expression of angiopoietin-1 (Ang-1), Tie2, and VEGF significantly decreased in the pulmonary arteries, and Tie2 receptor was inactivated in the lung. The expression of angiopoietin-3 (Ang-3), an endogenous antagonist of Ang-1, significantly increased in the intima under hypoxic conditions. CONCLUSIONS: Since both Ang-1/Tie2 and VEGF promote angiogenesis and vascular survival, and play protective roles in the adaptation of microvascular changes during the onset of PH, the downregulation of both Ang-1/Tie2 and VEGF and upregulation of Ang-3 appear to be associated with vascular rarefaction and the development of hypoxic PH.


Assuntos
Angiopoietina-1/antagonistas & inibidores , Angiopoietina-1/metabolismo , Regulação para Baixo/fisiologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Receptor TIE-2/metabolismo , Animais , Western Blotting , Caspase 3/metabolismo , Doença Crônica , Primers do DNA , Hipóxia/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Masculino , Neovascularização Patológica/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia
18.
Nihon Kokyuki Gakkai Zasshi ; 45(9): 715-9, 2007 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-17929475

RESUMO

We report a case of pulmonary arteriovenous fistula with multiple hepatic arterioportal shunts. A 23-year-old man was admitted for evaluation of a nodular shadow in the right lower lung field. Chest CT showed a homogeneous and well-defined nodular shadow in the right S7. 3-dimensional CT revealed an arteriovenous fistula composed of a feeding artery and a draining vein in the right S7. Abdominal enhanced CT revealed a diffusely heterogeneous pattern in the liver parenchyma and the portal vein staining diffusely at the late arterial phase. We diagnosed pulmonary arteriovenous fistula associated with multiple hepatic arterioportal shunts. Pulmonary arteriovenous fistula is often associated with hereditary hemorrhagic telangiectasia (HHT). This case did not meet the criteria for HHT at this time. However, we could not exclude the possibility of HHT because clinical manifestations of HHT become apparent after 40 years old among 10% of patients. The natural history and treatment of HHT are not clear. We concluded that we should be careful to detect possible manifestations as HHT when we diagnose and follow up patients with pulmonary arteriovenous fistula.


Assuntos
Fístula Arteriovenosa/complicações , Artéria Hepática/anormalidades , Veia Porta/anormalidades , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/diagnóstico , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Artéria Hepática/diagnóstico por imagem , Humanos , Circulação Hepática , Masculino , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X
19.
Respir Med Case Rep ; 21: 121-123, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28462081

RESUMO

Cutaneous adenoid cystic carcinoma (CACC) is an extremely rare neoplasm of head and neck region, and is characterized by propensity for local recurrence and perineural invasion. Late distant metastases occur usually to lungs. Although patients with lung metastases from CACC cannot be cured, long-term survival may be possible due to its slow-growing malignancy. We report a case of a 69-year-old female with lung metastases from CACC 23 years after initial surgery of scalp nodule.

20.
J Thorac Dis ; 9(12): 5052-5060, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29312710

RESUMO

BACKGROUND: Cigarette smoking remains a significant public health problem. However, current treatment programs have not yet succeeded in sufficiently reducing smoking rates. The study aimed to examine whether patients' recognition of "spirometric-lung-age (SLA)" estimated from spirometry data prompts smoking cessation. METHODS: From December 2010 to September 2011, participating smokers were prospectively enrolled into the standardized smoking cessation program (Visits 1-5 for 12 weeks) and assigned single-blindly to either SLA assessment or control groups. The SLA group was informed of the estimated age of their lungs from spirometry analysis and given an opportunity to recognize the difference from their actual chronological age, whereas the control group was not. The primary calculation of outcome was the smoking quit rate on Visit 5, whereas the secondary end-point was the proportion of patients who remained abstinent 1 year later. RESULTS: One hundred and twenty-six Japanese smokers (88 males) participated and were randomly assigned to the SLA group (n=52) or the control group (n=74). The smoking quit rate on Visit 5 was similar in the SLA assessment group and control group (59.6% vs. 41.9%; P=0.0700). However, the proportion of patients who remained abstinent 1 year later was similar in both groups (78.6% vs. 69.0%; P=0.5497). Multivariate logistic regression analysis after adjusting baseline characteristics demonstrated that telling patients their SLA, the use of varenicline, and age were significantly associated with smoking quit rate on Visit 5 whereas only age was associated with remaining abstinent 1 year later. CONCLUSIONS: Telling patients their SLA can become a useful tool prompting smoking cessation among Japanese smokers although other factors such as pharmacotherapy and age also influence the cessation of smoking.

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