RESUMEN
Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma , Bronquios , Peroxidasa del Eosinófilo , Células Epiteliales , Transición Epitelial-Mesenquimal , Factor de Crecimiento Transformador beta1 , Humanos , Asma/metabolismo , Asma/patología , Asma/fisiopatología , Asma/inmunología , Masculino , Femenino , Células Epiteliales/metabolismo , Peroxidasa del Eosinófilo/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Persona de Mediana Edad , Adulto , Bronquios/patología , Interleucina-5/metabolismo , Cromonas/farmacología , Citocinas/metabolismo , Línea Celular , Linfopoyetina del Estroma Tímico , Proliferación Celular , Movimiento Celular , Morfolinas/farmacología , Proteínas ADAMRESUMEN
INTRODUCTION: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. METHODS: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. RESULTS: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. CONCLUSION: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.
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Antibacterianos , Eritromicina , Microbioma Gastrointestinal , Enfermedad Pulmonar Obstructiva Crónica , Eritromicina/administración & dosificación , Eritromicina/farmacología , Animales , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Humanos , Anciano , Persona de Mediana Edad , Femenino , Pulmón/microbiología , Pulmón/efectos de los fármacos , Enfisema Pulmonar/microbiología , Enfisema Pulmonar/tratamiento farmacológico , Ratones Endogámicos C57BL , ARN Ribosómico 16SRESUMEN
BACKGROUND: Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome-wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS-supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. METHODS: A case-control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). RESULTS: The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048-3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001-4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. CONCLUSION: rs3117098 may be the risk factor for asthma in Chinese Zhuang population.
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Asma/genética , Butirofilinas/genética , Antígenos HLA-DQ/genética , Polimorfismo de Nucleótido Simple , Receptor Notch4/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/etnología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , MasculinoRESUMEN
Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous fungal infection caused by certain dematiaceous fungi (usually Fonsecaea, Phialophora, or Cladophialophora). Histologically, CBM is characterized by the presence of medlar bodies. However, the diagnosis is difficult because of the rarity of these pathognomonic presentations and the wide variety of presentations. Treatment of these infections is challenging as it lacks standardization. Herein, we report a case of chromoblastomycosis caused by Phialophora, in a 42-year-old immunocompetent male agriculturist from the humid and subtropical region of southern China. He had a 3-month history of pneumonia with intermittent fever, coughing, and expectoration. The infection subsequently spread to the bone and lymph nodes forming deep lesions and eventually resulting in osteolysis and lymphadenectasis. These subcutaneous nodules were observed after 9 months. Antifungal treatment was administered for 20 months leading to clinical improvement before the patient was lost to follow-up. This case is unique because such deep lesions are rare in immunocompetent individuals and because the initial onset was associated with pneumonia.
Asunto(s)
Antifúngicos/uso terapéutico , Cromoblastomicosis/tratamiento farmacológico , Phialophora/aislamiento & purificación , Administración Intravenosa , Administración Oral , Adulto , Cromoblastomicosis/complicaciones , Cromoblastomicosis/diagnóstico , Cromoblastomicosis/microbiología , Quimioterapia Combinada , Fiebre/tratamiento farmacológico , Fiebre/microbiología , Humanos , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/patología , Masculino , Osteólisis/diagnóstico , Osteólisis/tratamiento farmacológico , Osteólisis/microbiología , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tibia/diagnóstico por imagen , Tibia/microbiología , Resultado del TratamientoRESUMEN
OBJECTIVE: IL-1 receptor-like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people. METHODS: We performed a case-control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis. RESULTS: rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27-3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47-16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20-6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39-6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ. CONCLUSION: rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.
Asunto(s)
Asma/genética , Citocinas/genética , Proteína 1 Similar al Receptor de Interleucina-1/genética , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/etnología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Linfopoyetina del Estroma TímicoRESUMEN
Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfisema Pulmonar/inmunología , Anciano , Animales , Circulación Sanguínea , Diferenciación Celular , Células Cultivadas , Fumar Cigarrillos/efectos adversos , Modelos Animales de Enfermedad , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Enfisema Pulmonar/inducido químicamenteRESUMEN
BACKGROUND: Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. OBJECTIVES: To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. METHODS: The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. RESULTS: NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. CONCLUSIONS: NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.
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Células Dendríticas/inmunología , Trampas Extracelulares/inmunología , Neutrófilos/inmunología , Enfisema Pulmonar/inmunología , Contaminación por Humo de Tabaco/efectos adversos , Inmunidad Adaptativa , Animales , Linfocitos T CD4-Positivos/inmunología , Comunicación Celular/inmunología , Diferenciación Celular/inmunología , Técnicas de Cocultivo , Inmunidad Innata , Inflamación/inmunología , Masculino , Ratones Endogámicos BALB C , Enfisema Pulmonar/etiología , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
BACKGROUND: Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection. RESULTS: We used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype. CONCLUSIONS: The data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to provide novel ideas for prevention of P. marneffei-infection.
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Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Micosis/inmunología , Penicillium/inmunología , Penicillium/patogenicidad , Proteínas Adaptadoras Transductoras de Señales , Animales , Antígenos Fúngicos , Arginasa/metabolismo , Biomarcadores/metabolismo , Citocinas/metabolismo , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata/inmunología , Interleucina-12/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Micosis/microbiología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteómica , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.
Asunto(s)
Antígenos CD40/fisiología , Ligando de CD40/fisiología , Células Dendríticas/fisiología , Enfisema Pulmonar/inmunología , Humo/efectos adversos , Animales , Linfocitos T CD8-positivos , Diferenciación Celular , Células Cultivadas , Citocinas/biosíntesis , Citocinas/genética , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Recuento de Linfocitos , Ratones Endogámicos C57BL , Ratones Noqueados , Enfisema Pulmonar/etiología , Enfisema Pulmonar/metabolismo , Transducción de Señal , Fumar/efectos adversos , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Nicotiana/efectos adversosRESUMEN
Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 µg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.
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Corticoesteroides/farmacología , Dexametasona/farmacología , Eritromicina/farmacología , Leucocitos Mononucleares/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Glucocorticoides/metabolismo , Fumar/efectos adversos , Antiinflamatorios/farmacología , Western Blotting , Estudios de Casos y Controles , Quimioterapia Combinada , Fármacos Gastrointestinales/farmacología , Histona Desacetilasa 2/metabolismo , Humanos , Interleucina-8/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Células U937RESUMEN
BACKGROUND: Corticosteroids have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, whether inhaled corticosteroids (IC) alone have similar effects with systemic corticosteroid (SCS) is still unclear. OBJECTIVES: To compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AECOPD. METHODS: 30 AECOPD patients were randomly divided into two group. Budesonide group (15 cases) were treated with inhaled budesonide (3 mg Bid); methylprednisolone group (15 cases) were treated with systemic methylprednisolone (methylprednisolone acetate injectable suspension 40 mg Qd for three days and then methylprednisolone tablets 8 mg Bid). Observe symptoms, lung function, blood gas analysis and adverse effects of the patients in two groups. Peripheral blood samples were collected before and after treatment for 1 day, 4 days and 7 days. Interleukin-8 (IL-8) and TNF-α levels were determined by an enzyme linked immunosorbent assay (ELISA). Hs-CRP levels were detected by automatic biochemical analyzer. Western blotting was used to determine histone deacetylase 2 (HDAC2) protein expression. MEASUREMENTS AND MAIN RESULTS: Symptoms, pulmonary function and blood gas analysis were significantly improved after treatment in the two groups (P < 0.05) and no significant differences between the two groups (P > 0.05). There were no significant differences of IL-8, TNF-α and hs-CRP levels in the two groups (P > 0.05). Besides, the levels of HDAC2 protein expression before treatment were significantly lower comparing to that after treatment for 4 and 7 days. Incidence of adverse events (heart rate, blood pressure, glycemic, sleep condition, gastrointestinal symptoms) in budesonide group was lower than methylprednisolone group (P < 0.05). CONCLUSIONS: Inhaled budesonide and systemic methylprednisolone have the same effects on systemic inflammation of AECOPD. Inhaled corticosteroid alone could instead systemic corticosteroid in AECOPD treatment.
Asunto(s)
Antiinflamatorios/uso terapéutico , Budesonida/uso terapéutico , Inflamación/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Análisis de los Gases de la Sangre , Budesonida/administración & dosificación , Budesonida/efectos adversos , Proteína C-Reactiva/metabolismo , Vías de Administración de Medicamentos , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inflamación/inmunología , Interleucina-8/metabolismo , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Penicillium marneffei disseminates hematogenously and can infect most organs, though infection leading to osteolysis is extremely rare. We describe the clinical and laboratory features, management, and outcomes of patients with penicilliosis marneffei (PSM) with osteolytic lesions. METHODS: This retrospective study was conducted between January 1, 2003 and May 1, 2014 at the First Affiliated Hospital of Guangxi Medical University. Patients who presented with culture and/or histopathologic proof of disseminated PSM within osteolytic lesions were included. RESULTS: P. marneffei infection was diagnosed in 100 patients (65 HIV-infected and 35 HIV-negative). Fourteen patients, all HIV-negative, (14/35, 40%) had osteolytic lesions. The most common comorbidity was diabetes mellitus, though previous glucocorticoid therapy, ß-thalassemia, breast cancer, and Langerhans cell histiocytosis also occurred. Five patients had no comorbidity. Fever, malaise, ostealgia, weight loss, and anemia were the most common symptoms, followed by cutaneous lesions, lymphadenopathy, hepatosplenomegaly, cough, sputum, and stethalgia. Ostealgia, joint pain, and joint disorders were also recorded. White blood cell and neutrophil counts were increased (mean 22.3 ± 7.4 × 10(9) cells/L; mean 18.84 ± 4.5 × 10(9) cells/L, respectively). The most common sites were the vertebrae, skull and femur, ribs and ilium, though the clavicle, scapula, humerus, and tibia were also involved. Radiography and computed tomography (CT) showed multiple radiolucencies with moth-eaten bone destruction, periosteal proliferation, bone fracture, and surrounding soft-tissue swelling. Emission CT showed significantly increased uptake in many skeletal regions. Positron emission tomography/CT showed generalized lymphadenopathy, bone metabolic activity, and bone destruction. The (18) F-FDG standard uptake value was increased in the entire skeleton (mean 6.16). Twelve patients received antifungal therapy, four of whom died during treatment, and eight recovered, though four of these eight relapsed within 3-24 months. Two patients discontinued treatment because of severe multiple organ failure and died. CONCLUSIONS: Osteolysis is often overlooked in HIV-negative individuals with disseminated P. marneffei infection. However, P. marneffei involving the bone and leading to osteolysis may indicate severe systemic disturbance, and is characterized by a poor prognosis, high recurrence rate, and the need for prolonged antifungal treatment.
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Micosis/complicaciones , Osteólisis/microbiología , Penicillium/fisiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adulto , Anciano , Antifúngicos/uso terapéutico , China/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Micosis/diagnóstico por imagen , Micosis/tratamiento farmacológico , Micosis/epidemiología , Osteólisis/diagnóstico por imagen , Osteólisis/epidemiología , Penicillium/crecimiento & desarrollo , Radiografía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To analyze the clinical features of idiopathic sweet's syndrome (SS) that involves the lung. METHODS: A retrospective analysis was carried out on clinical data of 3 cases of patients with idiopathic SS that involves the lung who were admitted in the First Affiliated Hospital of Guangxi Medical University from August 2012 to December 2013. And relevant literatures were reviewed. RESULTS: Among the literatures reported between 1981 and 2014, there were a total of 39 SS cases involving the lung from both home and abroad, where 31 cases were accompanied with other diseases (i.e. blood diseases); the rest 8 cases without comorbidities were diagnosed as idiopathic SS, which were included into the analysis plus the 3 cases of this group. Among 11 cases, 6 cases were male while 5 cases were female, with the average age of 47 years old (25-72 years old). The patients all had the symptoms of fever, cough and dyspnea; painful and red pseudo-blisters rashes, pulmonary rale, hypoxemia and pulmonary exudative shadow. 3 cases had swollen lymph nodes. Rashes appeared before lung involvement in 6 cases while after lung involvement in 5 cases. In 11 cases, white blood cells, neutrophils, ESR and CRP were all significantly increased. Pulmonary CT showed unilateral or bilateral pulmonary invasive exudates and consolidation with pleural reaction. 3 cases showed restrictive ventilatory dysfunction. BAF fluid (9/9 cases) was given priority to neutrophils. Pulmonary pathology (9/9 cases) showed neutrophils-infiltrating interstitial pneumonia or organizing pneumonia, which were in accordance with the rash pathology (11/11 cases). 11 cases all had been misdiagnosed as invalid antibiotic treatment on pneumonia; where 9 cases were healed by glucocorticoid while 2 cases died. CONCLUSIONS: Idiopathic SS involving the lung is rare in clinical, which can appear before or after rash. Idiopathic SS is often misdiagnosed as bacterial pneumonia. Clinical features include the unknown increase of mature neutrophils, fever, dyspnea, and even respiratory failure, lung exudative or consolidation shadows, swollen lymph nodes and red and painful pseudo-blisters rashes. The involved area is often infiltrated by numerous neutrophils. The glucocorticoid has special effects, but easy to relapse, can also cause death.
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Síndrome de Sweet , Adulto , Anciano , China , Tos , Disnea , Femenino , Fiebre , Glucocorticoides , Humanos , Recuento de Leucocitos , Pulmón , Enfermedades Pulmonares Intersticiales , Masculino , Persona de Mediana Edad , Neutrófilos , Neumonía , Estudios RetrospectivosRESUMEN
BACKGROUND: Penicillium marneffei is the only dimorphic member of the genus and is an emerging pathogenic fungus that can cause fatal systemic mycosis. Penicillium marneffei disseminates hematogenously to other locations. Penicillium marneffei infection most commonly involves the skin, lungs, and reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported. Infection involving the trachea has not been previously reported. CASE PRESENTATION: We herein report a previously healthy 28-year-old male farmer from Guangxi Province without HIV who became infected with P. marneffei. The infection primarily affected the trachea, resulting in structural damage to the cartilage, tracheal stenosis, and tracheal absence. The infection also involved the lungs and lymph nodes. After antifungal treatment and surgery, his symptoms, signs, and lung imaging findings showed significant improvement. This is the first such case report. CONCLUSION: Penicillium marneffei infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. Penicillium marneffei hematogenously disseminates throughout the whole body. This is the first reported case of P. marneffei infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence.
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Antifúngicos/uso terapéutico , Micosis/microbiología , Penicillium/aislamiento & purificación , Enfermedades de la Tráquea/microbiología , Adulto , Animales , China , Humanos , Masculino , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Enfermedades de la Tráquea/diagnóstico , Enfermedades de la Tráquea/tratamiento farmacológicoRESUMEN
Background and Objective: The coronavirus disease 2019 (COVID-19) pandemic has taken a huge global toll on all fronts, creating new challenges for the diagnosis and treatment of respiratory diseases. For chronic management of asthma, on the one hand, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the asthma disease itself; on the other hand, in order to control the spread of the pandemic, forced isolation, mask-wearing and various disinfection measures also have an impact on the condition and medication of asthma patients. This article reviews the changes in chronic asthma management under the COVID-19 pandemic to provide reference for chronic disease management of asthma after the pandemic and for various public health emergencies in the future. Methods: Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Google Scholar, and EMBASE were searched. Key Content and Findings: COVID-19 has had a huge impact on the world, and has also brought new challenges to the diagnosis and treatment of asthma and chronic disease management. On the one hand, the existence of the 2019 novel coronavirus directly affects the asthma disease itself, on the other hand, due to the particularity of the asthma disease itself, different levels of isolation and controls can cause patients with different degrees of medical difficulties; in addition, the application of various disinfectants in the environment also increases the risk of acute attacks of asthma patients, as well as mask-wearing, vaccination, anxiety about the disease, panic, etc., all of which have posed various degrees of impact on the condition and psychology of asthma patients. Conclusions: The pandemic of COVID-19 has brought many difficulties to the chronic disease management of asthma, and has had a certain impact on the disease control of asthma patients. In the era with overflowing information, internet hospital is the current trend, and there is a long way to go for effectively penetrating medical resources virtually via the internet into chronic disease management of asthma.
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Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta-analyses have reported inconclusive results. Therefore, an updated meta-analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant 'null' genotype was compared with wild-type 'present' in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case-control studies were suitable for inclusion in the meta-analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192-1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293-2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051-1.781) and adults (OR = 1.859; 95% CI: 1.183-2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204-4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018-1.667), Africa (OR = 2.175; 95%CI: 1.560-3.031) and Latin America (OR = 2.265; 95%CI: 1.375-3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101-4.025) and Russian (OR = 2.747; 95% CI: 1.071-7.046) populations. This meta-analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.
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Asma/genética , Eliminación de Gen , Glutatión Transferasa/genética , Polimorfismo Genético/genética , Asma/epidemiología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Humanos , Oportunidad Relativa , Factores de RiesgoRESUMEN
Asthma is a common complex disorder characterized by hyper-responsiveness and chronic inflammatory airway disease in children and adults worldwide. The prevalence of asthma is increasing with each passing year. Long non-coding RNAs (lncRNAs), regarded as a potentially promising path, have received increasing attention in exploring the biological regulation of chronic airway diseases, although they have no or limited protein-coding capacity. This review highlights the functional roles and clinical significance of lncRNAs in the pathogenesis of asthma and provides directions for diagnosing and treating asthma in the future.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , ARN Largo no Codificante , Adulto , Niño , Humanos , ARN Largo no Codificante/genética , Asma/diagnóstico , Asma/genéticaRESUMEN
Background: Pulmonary enteric adenocarcinoma (PEAC) is a rare histological subtype of non-small-cell lung cancer (NSCLC) with a predominant (>50%) enteric differentiation component. The frequency of high microsatellite instability (MSI-H) is very low in lung cancer. EGFR tyrosine kinase inhibitors and immunotherapy are standard treatment for NSCLC patients, but their effectiveness in lung adenocarcinoma with pulmonary enteric differentiation is unknown. Case presentation: This report describes a 66-year-old man who was initially diagnosed with metastatic lung adenocarcinoma with EGFR mutation based on pleural fluid. A lung biopsy was obtained after 17 months of first-line icotinib treatment. Histological analysis of biopsy samples and endoscopic examination resulted in a diagnosis of adenocarcinoma with enteric differentiation. Next-generation sequencing of 1,021 genes showed EGFR E19del, T790M, and MSI-H, while immunohistochemical assay showed proficient expression of mismatch repair (MMR) proteins. Consequently, the patient was treated with osimertinib and had a progression-free survival (PFS) of 3 months. His treatment was changed to chemotherapy with/without bevacizumab for 6.5 months. Then, the patient was treated with one cycle of camrelizumab monotherapy and camrelizumab plus chemotherapy, respectively. The tumor continued to grow, and the patient suffered pneumonia, pulmonary fungal infections, and increased hemoptysis. He received gefitinib and everolimus and died 2 months later and had an overall survival of 30 months. Conclusion: In summary, our case describes a rare pulmonary enteric adenocarcinoma with an EGFR-activating mutation and MSI-H, responding to an EGFR tyrosine kinase inhibitor and poorly benefiting from an immune checkpoint inhibitor.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Receptores ErbB/genética , Inestabilidad de Microsatélites , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patología , InmunoterapiaRESUMEN
INTRODUCTION: To understand the risk factors of asthma, we combined genome-wide association study (GWAS) risk loci and clinical data in predicting asthma using machine-learning approaches. METHODS: A case-control study with 123 asthmatics and 100 controls was conducted in the Zhuang population in Guangxi. GWAS risk loci were detected using polymerase chain reaction, and clinical data were collected. Machine-learning approaches were used to identify the major factors that contribute to asthma. RESULTS: A total of 14 GWAS risk loci with clinical data were analyzed on the basis of 10 times the 10-fold cross-validation for all machine-learning models. Using GWAS risk loci or clinical data, the best performances exhibited area under the curve (AUC) values of 64.3% and 71.4%, respectively. Combining GWAS risk loci and clinical data, the XGBoost established the best model with an AUC of 79.7%, indicating that the combination of genetics and clinical data can enable improved performance. We then sorted the importance of features and found the top six risk factors for predicting asthma to be rs3117098, rs7775228, family history, rs2305480, rs4833095, and body mass index. CONCLUSION: Asthma-prediction models based on GWAS risk loci and clinical data can accurately predict asthma, and thus provide insights into the disease pathogenesis.
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INTRODUCTION: Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. METHODS: We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. CONCLUSIONS: Patients with T. marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.