RESUMEN
BACKGROUND: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP). OBJECTIVES: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy. METHODS: We conducted a genome-wide association study of HWP allergy in 452 cases and 2700 control subjects using 6.6 million genotyped or imputed single nucleotide polymorphisms. Replication was assessed by genotyping single nucleotide polymorphisms in independent samples comprising 45 patients with HWP allergy and 326 control subjects. RESULTS: Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 × 10-24 for rs9271588 and P = 2.96 × 10-24 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10-9). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQß1 amino acid positions 13 and 26) located in the P4 binding pockets on the HLA-DQ molecule achieved the genome-wide significance level (P < 5.0 × 10-8). CONCLUSIONS: Our data provide the first demonstration of genetic risk for HWP allergy and show that this genetic risk is mainly represented by multiple combinations of HLA variants.
Asunto(s)
Genotipo , Antígenos HLA-DQ/genética , Factores de Empalme de ARN/genética , Hipersensibilidad al Trigo/genética , Alérgenos/inmunología , Antígenos de Plantas/inmunología , Brotes de Enfermedades , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Hidrólisis , Japón/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Triticum/inmunología , Hipersensibilidad al Trigo/epidemiologíaRESUMEN
BACKGROUND: It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. METHODS: In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection. RESULTS: We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA. CONCLUSION: Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.
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Ácido Aspártico Endopeptidasas/análisis , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anciano , Biomarcadores de Tumor/análisis , Líquido del Lavado Bronquioalveolar , Broncoscopía/métodos , Femenino , Humanos , Pulmón/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Lung cancer is clearly the primary cause of cancer-related deaths worldwide. Recent molecular-targeted strategy has contributed to improvement of the curative effect of adenocarcinoma of the lung. However, such current treatment has not been developed for squamous cell carcinoma (SCC) of the disease. The new genome-wide RNA analysis of lung-SCC may provide new avenues for research and the development of the disease. Our recent microRNA (miRNA) expression signatures of lung-SCC revealed that clustered miRNAs miR-1/133a were significantly reduced in cancer tissues. Here, we found that restoration of both mature miR-1 and miR-133a significantly inhibited cancer cell proliferation, migration and invasion. Coronin-1C (CORO1C) was a common target gene of the miR-1/133a cluster, as shown by the genome-wide gene expression analysis and the luciferase reporter assay. Silencing of CORO1C gene expression inhibited cancer cell proliferation, migration and invasion. Furthermore, CORO1C-regulated molecular pathways were categorized by using si-CORO1C transfectants. Further analysis of novel cancer signaling pathways modulated by the tumor-suppressive cluster miR-1/133a will provide insights into the molecular mechanisms of lung-SCC oncogenesis and metastasis.
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Carcinoma de Células Escamosas/genética , Movimiento Celular/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Proteínas de Microfilamentos/genética , Anciano , Anciano de 80 o más Años , Azacitidina/farmacología , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Inhibidores Enzimáticos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ácidos Hidroxámicos/farmacología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Familia de Multigenes , Invasividad Neoplásica , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. METHODS: We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. RESULTS: Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. DISCUSSION: This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. CONCLUSION: These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.
Asunto(s)
Factor Activador de Células B/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Enfermedades Pulmonares Intersticiales/metabolismo , Pulmón/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedades del Tejido Conjuntivo/complicaciones , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Volumen Espiratorio Forzado , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Proteína D Asociada a Surfactante Pulmonar/sangre , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
Pulmonary involvement has been identified in human T-lymphotropic virus type I (HTLV-I) carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, the relationship between HTLV-I infection and lung disease is poorly understood. The occurrence of HTLV-I-specific immune responses in the lungs of patients infected with HTLV-I with pulmonary involvement was investigated. The frequency of HTLV-I-specific CD8+ cells and the amount of HTLV-I proviral DNA were determined in bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells (PBMCs) from five patients with HAM/TSP and one HTLV-I carrier who had pulmonary involvement. HTLV-I-specific CD8+ cells were detected by flow cytometry using human leukocyte antigen/antigen complex multimers. The analysis of bronchoalveolar lavage fluid revealed lymphocytosis in five of six patients. HTLV-I provirus was detected in the bronchoalveolar lavage fluid cells of all patients, and the proviral load in these cells was comparable to that in PBMCs. The frequency of HTLV-I-specific CD8+ cells in the bronchoalveolar lavage fluid cells was 5.1 times higher than that in PBMCs. Immunohistochemically, clusters formed by HTLV-I-specific CD8+ cells were detected in lung tissue by in situ tetramer staining. No samples were available from patients infected with HTLV-I without lung disorders. Whether accumulation of CD8+ cells is specific to patients with pulmonary involvement remains unclear. These results indicate that HTLV-I-specific CD8+ cells accumulate and HTLV-I-infected cells exist in the lungs of patients infected with HTLV-I with pulmonary involvement.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Enfermedades Pulmonares/inmunología , Pulmón/inmunología , Pulmón/virología , Adulto , Anciano , Anciano de 80 o más Años , Sangre/inmunología , Sangre/virología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/virología , Portador Sano/inmunología , Portador Sano/virología , Femenino , Infecciones por HTLV-I/virología , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Enfermedades Pulmonares/virología , Persona de Mediana Edad , Provirus/aislamiento & purificación , Carga ViralRESUMEN
BACKGROUND: Inhaled medication is the cornerstone of pharmacological treatment for asthma. Poor inhaler techniques are associated with poor asthma control and an increased risk of exacerbations. Leaflets and videos are provided by several pharmaceutical companies to explain the proper techniques to patients. We investigated the effects of instructional materials (leaflet and video) on the patient's inhaler techniques. METHODS: The subjects were 67 medical students at Kagoshima University. They all were provided with two types of inhalation devices: a dry powder inhaler (DPI) and a pressurized metered-dose inhaler (pMDI). The students were assigned to three groups: (1) leaflet, (2) video, and (3) combination (leaflet + video). Pulmonologists observed and assessed the students' use of the devices by using a validated checklist. The percentage of subjects who avoided critical errors was also assessed. Critical errors were errors that affected drug delivery to the lungs substantially. RESULTS: The percentage of overall competence and the number of steps that were mastered out of the 11 steps were higher in the combination group than those in the other two groups. However, only 40% in the combination group were able to successfully execute every critical step. The percentage of subjects who avoided critical errors was also higher in the combination group than in the other groups. CONCLUSIONS: A single form of instructional materials (leaflet or video) was insufficient for acquiring proper inhaler techniques. The combination of two learning materials may help patients with asthma acquire proper inhaler techniques and subsequently, improve their asthma control.
Asunto(s)
Asma , Inhaladores de Dosis Medida , Administración por Inhalación , Asma/tratamiento farmacológico , Inhaladores de Polvo Seco , Humanos , PulmónRESUMEN
A 50-year-old man presented with visual disturbance at a local ophthalmology clinic. He was given a diagnosis of uveitis and treated with oral corticosteroids; however, his visual disturbance did not improve and he was admitted to our hospital. A chest CT scan showed a pulmonary nodule in the upper lobe of the right lung, and right hilar and mediastinal lymphadenopathy. Transbronchial biopsy yielded a diagnosis of squamous cell carcinoma, and an ophthalmologic examination revealed bilateral diffuse uveal melanocytic proliferation (BDUMP). BDUMP is a rare manifestation of paraneoplastic syndrome, and the characteristics of the condition have not yet been clarified in detail. BDUMP carries a very poor visual prognosis, and in the present case, the patient's visual disturbance progressed rapidly despite systemic chemotherapy and corticosteroid therapy.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Melanocitos/patología , Síndromes Paraneoplásicos , Úvea/patología , Trastornos de la Visión/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We report a rare case of a thigh abscess which appeared during treatment of miliary tuberculosis. A 72-year-old woman with a history of diabetes mellitus was being treated for systemic sclerosis with prednisolone. She was then admitted to our hospital with fever, and chest computed tomography showed an abnormal shadow. She was given a diagnosis of miliary tuberculosis, and antituberculous therapy was initiated with isoniazid, rifampicin, ethambutol and pyrazinamide. Although this combination of antituberculous drugs was effective, 3 months after the initiation of treatment, a collection of fluid appeared in her left thigh. Further examination revealed the fluid to be positive for Mycobacterium tuberculosis on PCR and negative on mycobacterial culture. We thus diagnosed this phenomenon to be a paradoxical reaction.
Asunto(s)
Absceso/etiología , Tuberculosis Miliar/complicaciones , Absceso/microbiología , Anciano , Antituberculosos/administración & dosificación , Etambutol/administración & dosificación , Femenino , Humanos , Isoniazida/administración & dosificación , Mycobacterium tuberculosis/aislamiento & purificación , Pirazinamida/administración & dosificación , Muslo , Tuberculosis Miliar/tratamiento farmacológicoRESUMEN
Objective This multicenter, cross-sectional, non-interventional trial aimed to investigate adherence barriers to inhaled medicines when compared with oral medicines in Japanese patients with chronic obstructive pulmonary disease (COPD) and asthma. Methods The self-reporting "Adherence Starts with Knowledge 20" (ASK-20) questionnaire was administered for adherence barriers of inhaled and oral medicines to outpatients with regular clinic attendance. Results Patients with COPD and asthma reported different adherence barriers to inhaled medicines. Independent adherence barriers [odds ratio (95% confidence interval)] to inhaled medicines relative to those for oral medicines among patients with COPD and asthma were those related to item Q8 [ "I know if I am reaching my health goals"; 2.49 (1.39-4.47); p=0.0022] and item Q2 [ "I run out of my medicine because I do not get refills on time"; 2.69 (1.26-5.75); p=0.0127], respectively. Among patients with poor adherence to only inhaled medicines, those with COPD and asthma recognized item Q3 [ "consuming alcohol and taking medicines"; 6.63 (1.27-34.7); p<0.05] and item Q1 [ "forget to take medicines only sometimes"; 4.29 (1.83-10.0); p<0.05], respectively, were recognized as independent adherence barriers to inhaled medicines. The total ASK-20 scores and total barrier counts in patients with poor adherence to inhaled medicines were significantly higher than in those without poor adherence among patients with asthma (p=0.0057) but not those with COPD (p>0.05). Conclusion These results will aid in personalizing education on adherence to inhaled medicines among patients with COPD and asthma.
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Asma/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Fármacos del Sistema Respiratorio/administración & dosificación , Administración por Inhalación , Administración Oral , Adulto , Anciano , Asma/fisiopatología , Estudios Transversales , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Conocimientos, Actitudes y Práctica en Salud , Humanos , Japón , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Encuestas y Cuestionarios , Capacidad Vital/efectos de los fármacosAsunto(s)
Inmunoglobulina G/inmunología , Poliangitis Microscópica/terapia , Anciano , Antígenos CD/inmunología , Enfermedades Autoinmunes/diagnóstico , Diagnóstico Diferencial , Humanos , Inmunoglobulina G/sangre , Masculino , Poliangitis Microscópica/diagnóstico , Prevención Secundaria , Resultado del TratamientoRESUMEN
It is well known that lung cancer patients with severe chronic obstructive pulmonary disease (COPD) have a higher risk of postoperative complications than patients without COPD. However, the information regarding preoperative treatment to improve pulmonary function of the lung cancer patients with severe COPD is limited. Here, we report 3 lung cancer cases with severe COPD. Although all patients received medication without tiotropium bromide in combination with pulmonary rehabilitation for 1 or 2 months, their pulmonary function did not improve and the predicted postoperative FEV1/predicted FEV1 was below 40% in all cases. After the approval in Japan for use of tiotropium bromide in the treatment of COPD, all patients were treated with tiotropium bromide. The pulmonary function in all patients improved 2-4 weeks after the start of tiotropium bromide, and we performed lobectomy safely. Currently all patients maintain good pulmonary function without recurrence of lung cancer. We propose that treatment of tiotropium bromide might be one of the effective preoperative methods to improve pulmonary function of lung cancer patients with severe COPD.
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Broncodilatadores/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/uso terapéutico , Anciano , Humanos , Masculino , Complicaciones Posoperatorias/prevención & control , Bromuro de TiotropioRESUMEN
A 70-year-old man presented with a deteriorating fever and productive cough after the administration of drugs including L-carbocisteine against the common cold. Since chest radiograph revealed pulmonary infiltrates in the right lower lung field, he was admitted to our hospital, then L-carbocisteine was continued and antibiotics started. However, his symptoms, laboratory findings, and hypoxia worsened. Pulmonary infiltrates on his chest radiograph increased and chest CT demonstrated pulmonary consolidation with traction bronchiectasis and ground glass opacity with thickened of interlobular septae in the right lung field. Analysis of bronchoalveolar lavage fluid showed elevated numbers of total cells, neutrophils and eosinophils, and the CD4/CD8 ratio was 5.65. Under a suspected diagnosis of drug-induced pneumonia, we halted L-carbocisteine administration stopped and began corticosteroid therapy. Subsequently his symptoms and findings markedly improved. The drug lymphocyte stimulation test for L-carbocisteine using peripheral blood lymphocytes showed positive results. On the basis of the clinical course, laboratory and radiographic findings, we considered this case to possibly be drug-induced pneumonia due to L-carbocisteine. To our knowledge, this is possibly the first case of L-carbocisteine-induced pneumonia to be reported.
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Antiinfecciosos Locales/efectos adversos , Carbocisteína/efectos adversos , Neumonía/inducido químicamente , Anciano , Resfriado Común/tratamiento farmacológico , Humanos , MasculinoRESUMEN
We report a case of bronchial asthma attack with lactic acidosis and hypokalemia in a patient receiving high-dose inhalation of procaterol hydrochloride. A 28-year-old man was transferred to our hospital because of adynamia, nausea and dyspnea. He had used inhaled procaterol hydrochloride with a pressurized metered dose inhaler about 20 times before admission. On admission, there were no signs of shock state or hypoxemia and laboratory data showed hypokalemia, hyperglycemia and metabolic acidosis with elevated anion gap. Lactic acidosis was identified as the reason for the metabolic acidosis with elevated anion gap. Lactic acidosis improved after 12 hours. Lactic acidosis due to high dose inhalation of procaterol hydrochloride was suggested.
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Acidosis Láctica/inducido químicamente , Agonistas Adrenérgicos beta/efectos adversos , Asma/tratamiento farmacológico , Hipopotasemia/inducido químicamente , Procaterol/efectos adversos , Administración por Inhalación , Agonistas Adrenérgicos beta/administración & dosificación , Adulto , Humanos , Masculino , Procaterol/administración & dosificaciónRESUMEN
BACKGROUND: Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma and hypereosinophilia. For optimal treatment, prompt distinction of CSS from asthma is necessary; however, there are few serologic screening markers for this purpose. Vascular endothelial growth factor (VEGF), a vascular permeability factor, has been associated with other systemic vasculitis such as Wegener granulomatosis and giant-cell arteritis. OBJECTIVE: The aim of this study was to clarify the clinical value of the measurement of serum VEGF for the distinction of CSS from asthma. METHODS: We investigated serum VEGF levels in 18 CSS patients, 19 asthma patients, and 12 acute bronchitis patients. We also performed immunohistochemical analysis for VEGF. RESULTS: The serum VEGF levels of CSS patients were significantly higher than those of asthma patients and acute bronchitis patients. The sensitivity and specificity to distinguish CSS from asthma were 93.3% and 81.8%, respectively (cutoff, 600 pg/mL). Infiltrating eosinophils stained intensely positive for VEGF, and serum VEGF levels showed a significant correlation with peripheral eosinophil counts. Serum VEGF levels decreased significantly after therapy (p < 0.001). The infiltrating eosinophils in the CSS lesion stained positive for VEGF in the immunohistochemical analysis. CONCLUSION: VEGF is one of the useful screening markers for the distinction of CSS from asthma. We suggest that VEGF might be associated with the pathogenesis of CSS.
Asunto(s)
Síndrome de Churg-Strauss/diagnóstico , Factores de Crecimiento Endotelial Vascular/sangre , Enfermedad Aguda , Asma/diagnóstico , Bronquitis/diagnóstico , Síndrome de Churg-Strauss/sangre , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Piel/metabolismo , Factores de Crecimiento Endotelial Vascular/análisisRESUMEN
We report the case of a 33-year-old woman with limited systemic sclerosis and chronic progressive sensory ataxic neuropathy. Sural nerve biopsy showed loss of myelinated fibers mostly those of large diameter, axonal degeneration and infiltration of macrophages, but no signs of vasculitis. Physical examination, laboratory testing, neurophysiological and neuroradiological examinations suggested that the dorsal root was primarily affected in this patient. Cytokine analysis by multiplex bead array assay revealed that IL-1beta and GM-CSF were increased both in serum and CSF. Although her symptoms did not respond to corticosteroid therapy, intravenous immunoglobulin (IVIg) therapy resulted in marked improvement. IVIg could be effective in case of immune-mediated reversible neuronal dysfunction associated with collagen disease without vasculitis.
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Ataxia/complicaciones , Enfermedades del Sistema Nervioso Periférico/complicaciones , Trastornos de la Sensación/complicaciones , Adulto , Ataxia/metabolismo , Ataxia/patología , Ataxia/terapia , Citocinas/metabolismo , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/terapia , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/terapia , Trastornos de la Sensación/metabolismo , Trastornos de la Sensación/patología , Trastornos de la Sensación/terapia , Nervio Sural/patología , Nervio Sural/ultraestructuraRESUMEN
Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the lungs. However, there are little serological markers that predict its prognosis or severity of pulmonary involvement. Vascular endothelial growth factor (VEGF) is an angiogenic mediator, which has been reported to be elevated in systemic vasculitis. In this study, we measured serum VEGF levels in 22 MPA patients with pulmonary involvement. We also investigated VEGF expression in pulmonary cells using flow cytometry analysis. We found that serum VEGF levels in MPA patients were significantly higher than those in respiratory or urinary tract infection. The serum VEGF levels decreased in parallel with the improvement of MPA symptoms. The serum VEGF levels in MPA patients who died within 5 years were significantly higher than those who survived more than 5 years. The sensitivity of VEGF levels to distinguish MPA patient with poor prognosis from those with good prognosis was 90.9%, and specificity was 81.8% (cutoff value = 802.5 pg/ml). The serum VEGF levels showed significant positive correlation with the composite physiological index, which indicates the severity of pulmonary lesion. In flow cytometry analysis, CD11b positive bronchoalveolar lavage fluid cells expressed VEGF. Immunohistochemically, alveolar macrophages, tissue infiltrating inflammatory cells and alveolar epithelial cells stained positive for VEGF. Measurement of serum VEGF levels in MPA might become one of the markers for prognosis and the severity of pulmonary involvement in MPA. VEGF might contribute to the development of pulmonary lesion of MPA.
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Enfermedades Pulmonares/diagnóstico , Poliarteritis Nudosa/diagnóstico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Anciano , Análisis de Varianza , Líquido del Lavado Bronquioalveolar/citología , Proliferación Celular , Citocinas/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Inmunohistoquímica , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/patología , Macrófagos/patología , Masculino , Microcirculación/fisiología , Poliarteritis Nudosa/complicaciones , Poliarteritis Nudosa/patología , Pronóstico , Circulación Pulmonar/fisiología , Estudios RetrospectivosRESUMEN
A 48-year-old woman was admitted with dyspnea on effort. She suffered from adult T-cell leukemia and received peripheral blood stem cell transplantation (PBSCT). Eight months after the PBSCT, she developed dyspnea on effort and was treated with bronchodilator, inhaled corticosteroid, anti-leukotriene drug, theophylline and oxytropium bromide. However her symptoms progressed and she was admitted. We diagnosed bronchiolitis obliterans syndrome (BOS) because of obstructive pulmonary dysfunction, diffuse patchy high density of the lung field on chest computed tomography and decreased ventilation with peripheral patchy accumulation on ventilation scintigraphy. She was treated with corticosteroid and cyclosporine A and her symptoms and her pulmonary function were improved. However, in parallel with corticosteroid tapering, her symptoms and pulmonary functions worsened. Treatment with Tiotropium bromide was started and her pulmonary function improved significantly. Her pulmonary function did not worsen and tapering steroid dose was successfully achieved. PBSCT was reported to up-regulate the muscarinic receptor activity in lung. Tiotropium bromide might become one additional option for the treatment of BOS.
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Bronquiolitis Obliterante/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Derivados de Escopolamina/uso terapéutico , Bronquiolitis Obliterante/etiología , Esquema de Medicación , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/terapia , Persona de Mediana Edad , Inducción de Remisión , Bromuro de TiotropioRESUMEN
Case 1 is a 78-year-old woman in whom lung adenocarcinoma with multiple brain metastasis (cT2N3M1, stage IV) was diagnosed. She was treated with Gefitinib alone. Her lung tumor and metastatic brain lesions decreased 6 months after the start of therapy. She has no recurrence and is still alive with a good performance status after 25 months. Case 2 is an 80-year-old woman in whom lung adenocarcinoma with multiple brain (cT2N3M1, stage IV) was diagnosed. She was also treated with Gefitinib alone and her lung tumor and metastatic brain becomes improved 6 months after the start of therapy. She maintained a good performance status for more than 2 years (29 months). However, 29 months after beginning treatment, she had recurrence in bone and died 2 months later, 31 months after the start of therapy. The prognosis of non-small cell lung cancer with multiple brain metastasis is very poor and the efficacy of chemotherapy for the treatment of multiple brain metastases is limited, and longterm survival remains disappointing. We report two lung adenocarcinoma patients with multiple brain metastasis who survived more than 2 years by treatment with Gefitinib alone.