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1.
Int J Chron Obstruct Pulmon Dis ; 18: 1077-1090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37309393

RESUMO

Purpose: In COPD, exacerbation of the disorder causes a deterioration in the quality-of-life and worsens respiratory dysfunction, leading to a poor prognosis. In recent years, nutritional indices have been reported as significant prognostic factors in various chronic diseases. However, the relationship between nutritional indicators and prognosis in elderly subjects with COPD has not been investigated. Patients and methods: We enrolled 91 subjects who received COPD assessment tests (CAT), spirometry, blood tests, and multidetector computed tomography (MDCT). We divided the subjects into two groups according to age (<75 years (n=57) and ≥ 75 years (n=34)). The prognostic nutritional index (PNI) was used to assess immune-nutritional status and was calculated as 10 x serum albumin + 0.005 x total lymphocyte count. We then examined the relationship between PNI and clinical parameters, including exacerbation events. Results: There was no significant correlation between the PNI and CAT, the FEV1%pred, or low attenuation volume percentage (LAV%). In the elderly group, there were significant differences between the groups with or without exacerbation in the CAT and PNI (p=0.008, p=0.004, respectively). FEV1%pred, neutrophil-to-lymphocyte ratio (NLR) and LAV% did not differ between the two groups. The analytical model combining CAT and PNI improved the prediction of exacerbations in the elderly subjects (p=0.0068). Conclusion: In elderly subjects with COPD, CAT were associated significantly with the risk of COPD exacerbation, with PNI also a potential predictor. The combined assessment of CAT and PNI may be a useful prognostic tool in subjects with COPD.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Avaliação Nutricional , Prognóstico , Prednisona
2.
Rinsho Ketsueki ; 64(3): 224-229, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37019678

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder in which an activated complement causes intravascular hemolysis of erythrocytes that do not have complement regulators. It is critical to monitor the rapid progression of hemolysis caused by infection and thrombosis. As far as we can tell, this is the first report of 5 COVID-19 patients with PNH in Japan. Three patients were being treated with ravulizumab, one with eculizumab, and one with crovalimab. All five cases had received two or more COVID-19 vaccinations. COVID-19 was classified as mild in four cases and moderate in one. None of the cases required the use of oxygen, and none became severe. All of them experienced breakthrough hemolysis, and two required red blood cell transfusions. In any case, no thrombotic complications were observed.


Assuntos
COVID-19 , Hemoglobinúria Paroxística , Trombose , Humanos , Hemoglobinúria Paroxística/terapia , Hemólise , Anticorpos Monoclonais , Eritrócitos
3.
Acad Radiol ; 29 Suppl 2: S215-S225, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34144888

RESUMO

RATIONALE AND OBJECTIVES: Changes in the geometry of the chest wall due to lung hyperinflation occur in COPD. However, the quantitative assessment of impaired lung motions and its association with the clinical characteristics of COPD patients are unclear. This study aimed to investigate the respiratory kinetics of COPD patients by dynamic MRI. MATERIALS AND METHODS: This study enrolled 22 COPD patients and 10 normal participants who underwent dynamic MRI and pulmonary function testing (PFT). Changes in the areas of the lung and mediastinum during respiration were compared between the COPD patients and the normal controls. Relationships between MRI, CT parameters, and clinical measures that included PFT results also were evaluated. RESULTS: Asynchronous movements and decreased diaphragmatic motion were found in COPD patients. COPD patients had a larger ratio of MRI-measured lung areas at expiration to inspiration, a smaller magnitude of the peak area change ratio, and a smaller mediastinal-thoracic area ratio than the normal participants. The lung area ratio was associated with FEV1/FVC, predicted RV%, and CT lung volume/predicted total lung capacity (pTLC). The lung area ratio of the right lower and left lower lungs was significantly correlated with emphysema of each lower lobe. The expiratory mediastinal-thoracic area ratio was associated with FEV1% predicted and RV/TLC. CONCLUSION: Changes in the lung areas of COPD patients as shown on MRI reflected the severity of airflow limitation, hyperinflation, and the extent of emphysema. Dynamic MRI provides essential information about respiratory kinetics in COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Expiração , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem
4.
Am J Respir Cell Mol Biol ; 63(6): 806-818, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32915635

RESUMO

Excessive release of neutrophil extracellular traps (NETs) has been implicated in several organ fibrosis, including pulmonary fibrosis. NETs constitute a phenomenon in which decorated nuclear chromatin with cytosolic proteins is released into the extracellular space. PAD4 (peptidylarginine deiminase 4) plays an important role in the formation of NETs. However, the role of NETs in the pathogenesis of pulmonary fibrosis remains undefined. Here, we identified NETs in the alveolar and interstitial lung space of mice undergoing bleomycin (BLM)-induced lung fibrosis, which was suppressed by a pan-PAD inhibitor, Cl-amidine. In vitro, BLM directly induced NETs in blood neutrophils, which was also inhibited by Cl-amidine. Furthermore, Padi4 gene knockout (PAD4-KO) in mice led to the alleviation of BLM-induced NETs and pulmonary fibrosis and to the expression of inflammatory and fibrotic genes. PAD4 deficiency prevented decreases in alveolar epithelial and pulmonary vascular endothelial cell numbers and increases in ACTA2-positive mesenchymal cells and S100A4-positive fibroblasts in the lung. Hematopoietic cell grafts from PAD4-KO mice, not wild-type mice, resolved BLM-induced lung fibrosis and fibrotic gene expression in wild-type and PAD4-KO mice, suggesting that expression of PAD4 in hematopoietic cells may be involved in the development of lung fibrosis. These data suggest that PAD4 deficiency could ameliorate BLM-induced formation of NETs and lung fibrosis, suggesting that this pathway could serve as a therapeutic target for pulmonary fibrosis treatment.


Assuntos
Armadilhas Extracelulares/genética , Pulmão/patologia , Neutrófilos/metabolismo , Proteína-Arginina Desiminase do Tipo 4/deficiência , Fibrose Pulmonar/patologia , Animais , Bleomicina/farmacologia , Modelos Animais de Doenças , Armadilhas Extracelulares/metabolismo , Fibrose/metabolismo , Fibrose/patologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/patologia , Fibrose Pulmonar/metabolismo
5.
PLoS One ; 15(9): e0239066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941486

RESUMO

BACKGROUND: Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial fibrosis. However, ambiguous diagnostic criteria and, particularly, the absence of objective methods to quantify emphysematous/fibrotic lesions in patients with CPFE confound the interpretation of the pathophysiology of this syndrome. We analyzed the relationship between objectively quantified computed tomography (CT) measurements and the results of pulmonary function testing (PFT) and clinical events in CPFE patients. MATERIALS AND METHODS: We enrolled 46 CPFE patients who underwent CT and PFT. The extent of emphysematous lesions was obtained by calculating the percent of low attenuation area (%LAA). The extent of fibrotic lesions was calculated as the percent of high attenuation area (%HAA). %LAA and %HAA values were combined to yield the percent of abnormal area (%AA). We assessed the relationships between CT parameters and other clinical indices, including PFT results. Multivariate analysis was performed to examine the association between the CT parameters and clinical events. RESULTS: A greater negative correlation with percent predicted diffusing capacity of the lung for carbon monoxide (DLCO %predicted) existed for %AA (r = -0.73, p < 0.001) than for %LAA or %HAA alone. The %HAA value was inversely correlated with percent predicted forced vital capacity (r = -0.48, p < 0.001), percent predicted total lung capacity (r = -0.48, p < 0.01), and DLCO %predicted (r = -0.47, p < 0.01). Multivariate logistic regression analysis found that %AA showed the strongest association with hospitalization events (odds ratio = 1.20, 95% confidence interval = 1.01-1.54, p = 0.029). CONCLUSION: Quantitative CT measurements reflected deterioration in pulmonary function and were associated with hospitalization in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and the clinical course of patients with CPFE.


Assuntos
Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Feminino , Humanos , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Enfisema Pulmonar/complicações , Enfisema Pulmonar/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Testes de Função Respiratória
6.
PLoS One ; 14(12): e0227141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887184

RESUMO

BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features. However, there have been few reports on the structural lung abnormalities found in this patient population. Multi-detector computed tomography (MDCT) can detect emphysematous low-attenuation areas (LAA) within the lung, airway thickness (wall area percentage, WA%), and the loss of pulmonary vasculature as the percentage of small pulmonary vessels with cross-sectional area (CSA) less than 5 mm2 (%CSA<5). We analyzed differences in structural lung changes over time between patients with COPD and those with COPD with asthma-like features using these CT parameters. MATERIAL AND METHODS: We performed pulmonary function tests (PFTs), MDCT, and a COPD assessment test (CAT) in 50 patients with COPD and 29 patients with COPD with asthma-like features at the time of enrollment and two years later. We analyzed changes in clinical parameters and CT indices over time and evaluated differences in structural changes between groups. RESULTS: The CAT score and FEV1 did not significantly change during the follow-up period in either group. Emphysematous LAA regions significantly increased in both groups. The %CSA<5 showed a small but significant increase in COPD patients, but a significant decrease in patients with COPD with asthma-like features. The WA% at the distal bronchi was significantly decreased in COPD, but did not significantly change in COPD with asthma -like features. CONCLUSION: Emphysematous LAA increased in patients with COPD with and without asthma-like features. The %CSA<5 and WA% at the distal bronchi did not change in parallel with LAA. Furthermore, changes in %CSA<5 were significantly different between patients with COPD and those with COPD with asthma-like features. Patients with COPD with asthma-like features may have different longitudinal structural changes than those seen in COPD patients.


Assuntos
Asma/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/diagnóstico por imagem , Idoso , Asma/etiologia , Asma/fisiopatologia , Feminino , Seguimentos , Humanos , Japão , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória
7.
In Vitro Cell Dev Biol Anim ; 55(8): 656-664, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297698

RESUMO

The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, high mobility group box 1 (HMGB1), S100A12, and N-epsilon-(carboxymethyl) lysine (CML), on human fibronectin-directed human fetal lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited, HFL-1 migration in a concentration-dependent manner. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE, but not Toll-like receptor 4. S100A12 did not exert a chemoattractant effect, but inhibited HFL-1 chemotaxis and/or chemokinesis. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK) but not through nuclear factor-kappa B, protein kinase A, phosphatase and tensin homolog deleted on chromosome 10, or cyclooxygenase. In addition, western blot analysis showed that S100A12 augmented p38 MAPK activity in the presence of human fibronectin. In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.


Assuntos
Movimento Celular/efeitos dos fármacos , Fibroblastos/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteína S100A12/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fibronectinas/farmacologia , Proteína HMGB1/metabolismo , Humanos , Ligantes , Pulmão/citologia , Receptor 4 Toll-Like/metabolismo
8.
Gen Thorac Cardiovasc Surg ; 67(3): 332-335, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29804176

RESUMO

A 27-year-old female patient had presented progressing exertional dyspnea due to pulmonary hypertension. Chest CT revealed diffusely spread patchy ground-glass opacities sparing subpleural parenchymal areas suggesting the diagnosis of pulmonary veno-occlusive disease (PVOD). Despite the diagnosis of PVOD, she was somehow managed by a repetitive escalation of the epoprostenol dose and oxygen supply during the 12-month waiting period until successful bilateral lung transplantation was performed. Pathology demonstrated capillary proliferation in alveolar septae with scarce lesions of narrowed and/or occluded postcapillary small veins, leading to the final diagnosis of pulmonary capillary hemangiomatosis (PCH), not PVOD. We herein present a case of PCH diagnosed after lung transplantation with a focus on its etiology and a key to clinical diagnosis.


Assuntos
Granuloma Piogênico/diagnóstico , Pneumopatias/diagnóstico , Adulto , Diagnóstico Diferencial , Dispneia/etiologia , Feminino , Granuloma Piogênico/complicações , Granuloma Piogênico/patologia , Granuloma Piogênico/cirurgia , Humanos , Hipertensão Pulmonar/etiologia , Pneumopatias/complicações , Pneumopatias/patologia , Pneumopatias/cirurgia , Transplante de Pulmão , Tomografia Computadorizada por Raios X
9.
Pulm Circ ; 9(4): 2045894019896696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31908771

RESUMO

Pulmonary capillary hemangiomatosis (PCH) is a very rare and refractory disease characterized by capillary angioproliferation. The updated classification of pulmonary hypertension categorizes PCH into a subgroup of pulmonary arterial hypertension (PAH) alongside pulmonary veno-occlusive disease (PVOD). However, the definitive diagnosis of PCH only with noninvasive tools remains difficult. The aim of this study was to elucidate the radiological and physiological characteristics of PCH. We searched for cases of pathologically confirmed PCH in the English literature published between 2000 and 2018. We identified 26 cases among 39 studies. Then, we extracted and evaluated the relevant clinical information in all cases with available data. On chest computed tomography (CT), ground-glass opacities (GGOs) were observed in 92% of the cases, in which poorly defined nodular pattern was the most common (88%). GGOs in a bat-wing distribution were observed in one case. Septal lines and lymph node enlargement were observed less frequently (each 19%, 12%). Seven cases (27%) had overlapping abnormalities. Diffusing capacity of the lung for carbon monoxide (DLCO) was remarkably decreased. Alveolar hemorrhage by histological findings or bronchoalveolar lavage (BAL) was observed in seven cases. The present study showed that the most characteristic findings of CT in PCH was centrilobular GGOs with a poorly defined nodular pattern, and septal lines and lymph node enlargement were seen less frequently. Alveolar hemorrhage detected by BAL and decreased DLCO may also be helpful to recognize the possibility of PCH like PVOD.

10.
J Appl Toxicol ; 39(4): 658-671, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30565269

RESUMO

Drug-induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting-edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug-induced lung injury. We used a mouse model of bleomycin-induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory-to-fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether-type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D2 , were elevated on day 2, and those of 5- and 15-lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12-lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti-inflammatory responses in the inflammatory phase, phospholipidosis and anti-inflammatory responses in the inflammatory-to-fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug-induced lung injury.


Assuntos
Bleomicina/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/química , Fibrose , Lipidômica , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/sangue , Lesão Pulmonar/patologia , Masculino , Camundongos
11.
Circ J ; 82(5): 1428-1436, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29540628

RESUMO

BACKGROUND: Several new treatments for chronic thromboembolic pulmonary hypertension (CTEPH) have appeared in recent years, which have led to changes in the treatment algorithm. Changes in survival rates and prognostic factors, however, have not been estimated so far.Methods and Results:Two hundred and eighty patients were diagnosed with CTEPH at Chiba University Hospital between June 1986 and June 2016. Survival rate was investigated by date of treatment initiation (group 1, 1986-1998; group 2, 1999-2008; group 3, 2009-2016). Survival rates were also evaluated by treatment strategy: balloon pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and medical treatment. Group 3 had significantly better disease-specific survival than groups 1 and 2 (5-year survival: 91.9% vs. 67.1%, 77.0%, respectively). For the non-PEA (BPA+medication) strategy, group 3 had better disease-specific survival than groups 1 and 2 (5-year survival: 94.9% vs. 54.6%, 74.2%, respectively). The PEA strategy had significantly better survival than the medication strategy in groups 1 and 2, whereas no difference was observed between the BPA, PEA, and medication strategies in group 3. CONCLUSIONS: Survival in CTEPH in the recent era has significantly improved, especially in non-PEA patients. BPA and selective pulmonary vasodilators could improve survival in the non-PEA group. In the present study, no difference in survival was found between PEA and non-PEA.


Assuntos
Angioplastia com Balão , Endarterectomia , Hipertensão Pulmonar , Embolia Pulmonar , Adulto , Idoso , Doença Crônica , Intervalo Livre de Doença , Feminino , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/mortalidade , Embolia Pulmonar/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Kekkaku ; 89(8): 711-6, 2014 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-25283012

RESUMO

An 88-year-old woman with rheumatoid arthritis who had started etanercept treatment in July 2011 was referred to our hospital in February 2012 for right-sided pleural effusion. Chest computed tomography showed right pleural effusion, partial swelling of a calcified mediastinal lymph node, and mid-esophageal thickening of the mucosal wall. Gastroendoscopy showed mid-esophageal ulceration. Histological examination of biopsy specimens from this ulceration revealed noncaseating granulomas with Langhans giant cells. Ziehl-Neelsen staining of this section was positive for acid-fast bacilli. Polymerase chain reaction analysis of gastric juice was positive for Mycobacterium tuberculosis; we therefore diagnosed the patient with esophageal tuberculosis. However, since abdominal computed tomography showed swelling of mesenteric lymph nodes, we also suspected intestinal tuberculosis. Colonoscopy showed multiple ileal erosions; histological analyses of biopsied specimens revealed granulomas with Langhans giant cells, similar to the esophageal findings. We finally diagnosed the patient with both esophageal and intestinal tuberculosis. After anti-tuberculosis treatment, the right pleural effusion disappeared and the abdominal lesions improved. Although mycobacterial involvement of both the esophagus and intestine is rare in immunocompromised and immunocompetent hosts, differential diagnosis of these diseases is likely to become more important.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Doenças do Esôfago/etiologia , Imunoglobulina G/efeitos adversos , Tuberculose Gastrointestinal/etiologia , Idoso de 80 Anos ou mais , Etanercepte , Feminino , Humanos , Receptores do Fator de Necrose Tumoral
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