RESUMO
BACKGROUND: Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response. METHODS: We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE2, PGI2, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI2 on the cough response by employing a PGI2 receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction. RESULTS: The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE2, PGI2, and Cys-LTs, and the ratio of PGI2/PGE2 were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI2 receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE2, PGI2, and Cys-LTs and the ratio of PGI2/PGE2. CONCLUSIONS: Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.
Assuntos
Asma/metabolismo , Brônquios/fisiologia , Tosse/metabolismo , Animais , Asma/fisiopatologia , Testes de Provocação Brônquica , Broncoconstrição , Tosse/fisiopatologia , Cisteína/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Epoprostenol/antagonistas & inibidores , Epoprostenol/metabolismo , Cobaias , Humanos , Leucotrienos/metabolismo , Metabolismo dos Lipídeos , Masculino , Cloreto de MetacolinaRESUMO
Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.
Assuntos
Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Radiografia Torácica/métodos , Idoso , Asma/diagnóstico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Fluticasona/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Glicopirrolato/análogos & derivados , Glicopirrolato/uso terapêutico , Humanos , Indanos/uso terapêutico , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Espirometria , Brometo de Tiotrópio/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Molecular targeted therapy has been developed as an innovative treatment for metastatic cancer. Epidermal growth factor receptor (EGFR) mutation is one of the most important and frequent oncogenic drivers in non-small-cell lung cancer, and EGFR-tyrosine kinase inhibitors are indispensable drugs for mutation-positive patients. Currently, the acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a problem, the mechanism of which has not been elucidated. The histological transformation from original adenocarcinoma to small-cell carcinoma is rare; however, it has been detected in many cases after EGFR-TKI treatment. This study aimed to evaluate mutational status in two different histological types and further elucidate the molecular pathogenesis. METHODS: Three patients with EGFR-mutant lung cancer who underwent a histological transformation to small-cell carcinoma after growth factor receptor-TKI treatment were enrolled in this study. Two samples per patient were collected from histologically different lesions, and DNA samples were extracted from formalin-fixed, paraffin-embedded tumor tissues. The paired samples were subjected to next-generation sequencing of 160 cancer-related genes. Based on the sequencing results, the expression levels of related proteins were validated using reverse-transferase polymerase chain reaction and immunohistochemical staining. RESULTS: The following five variants were common among the three cases: MTOR, JAK1, NOTCH2, CSF1R, and MAP2K2. The former four variants were additive to small-cell carcinoma, and the last variant was lost. Both TP53 and Rb1 alterations were detected in adenocarcinoma. Notch2 expression was negative in small-cell carcinoma in both reverse-transcriptase polymerase chain reaction analysis and immunohistochemical staining. ASCL1 expression increased after histological transformation detected using both methods in one case, only these samples were evaluable. CONCLUSIONS: Notch and ASCL1 signaling are the master regulators of neuroendocrine differentiation in small-cell lung carcinoma. Our results suggest that the Notch-ASCL1 axis may also play an essential role in the transformation of small-cell carcinoma under TP53 and RB1 inactivation.
RESUMO
BACKGROUND: Nafamostat mesylate (NM) may prove to be one of the key drugs effective against coronavirus disease 2019 (COVID-19) because of its anti-viral properties and the potential to manage coagulopathy. However, NM tends to increase serum potassium levels. CASE SUMMARY: We observed hyperkalemia immediately after NM administration (200 mg/d) in four consecutive patients who were admitted to the Kanazawa University Hospital with severe COVID-19 pneumonia. Urinary potassium excretion decreased after NM administration in three patients who underwent urinalysis. CONCLUSION: NM is likely to produce hyperkalemia in patients with COVID-19. Therefore, it is necessary to monitor serum potassium values closely after NM initiation in COVID-19 patients who need respiratory support.
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OBJECTIVE: In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium Respimatâ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting ß2-adrenoceptor agonists (LABA). METHODS: The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. RESULTS: All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). CONCLUSIONS: Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.
Assuntos
Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Japão , Masculino , Antagonistas Muscarínicos/administração & dosagem , Estudos Retrospectivos , Fumar/efeitos adversos , Resultado do TratamentoRESUMO
A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.
Assuntos
Anemia Hemolítica Autoimune/epidemiologia , Período Pós-Operatório , Timoma/epidemiologia , Timoma/fisiopatologia , Neoplasias do Timo/epidemiologia , Neoplasias do Timo/fisiopatologia , Anemia Hemolítica Autoimune/diagnóstico , Teste de Coombs , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgiaRESUMO
We present a rare case of gingival cancer with pulmonary metastases that developed life-threatening complete atrioventricular block and ventricular fibrillation as a result of myocardial metastases. This case suggests that implantable cardioverter defibrillators significantly improve the quality of life in these patients and maintain their performance status.