RESUMO
Thoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was "Unclassifiable" (54%). Histologically, "Unclassifiable" was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and "Unclassifiable" was the commonest pattern radiologically and histologically.
Assuntos
Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA. RESULTS: miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6. CONCLUSIONS: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.
Assuntos
Quimiocinas/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-13/farmacologia , MicroRNAs/genética , Brônquios , Linhagem Celular , Quimiocinas/metabolismo , Humanos , Fosforilação , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mucosa Respiratória/metabolismo , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a "definite" or "possible" usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.
Assuntos
Artrite Reumatoide/complicações , Fibrose Pulmonar Idiopática/mortalidade , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Capacidade VitalRESUMO
Pulmonary involvement is a frequent manifestation of connective tissue disease (CTD)-related thoracic disease. It is important to characterize the underlying pattern when pulmonary involvement occurs in a patient with CTD, and to exclude other causes. A systematic approach, evaluating each compartment of the lung (airway, interstitium, pleura, pulmonary vasculature) may be helpful. In complex cases, a multidisciplinary approach should be considered, potentially including the pulmonologist, rheumatologist, radiologist, pathologist, and sometimes the infectious disease specialist or oncologist. New techniques, such as quantitative computed tomography and MRI, are expected to be helpful for evaluation and management of CTD-associated thoracic disease.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Diagnóstico por Imagem , Doenças Torácicas/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Doenças do Tecido Conjuntivo/complicações , Humanos , Doenças Torácicas/etiologiaRESUMO
Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.
Assuntos
Infecções Comunitárias Adquiridas/patologia , Infecção Hospitalar/patologia , Pneumonia Aspirativa/patologia , Pneumonia/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/mortalidade , Comorbidade , Infecção Hospitalar/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Japão/epidemiologia , Masculino , Pneumonia/mortalidade , Pneumonia Aspirativa/mortalidade , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.
RESUMO
A 74-year-old Japanese man with myelodysplastic syndrome (MDS) received chemotherapy with azacitidine. From the second day after starting the administration, he complained of fever, cough and shortness of breath. Chest roentgenography and computed tomography showed consolidations and ground-glass opacities. His symptoms grew from worse to life-threatening. We diagnosed him with azacitidine-induced pneumonitis and began administering corticosteroids. Thereafter, his symptoms and radiographic abnormalities improved. Azacitidine is a hypomethylating agent that improves the survival of MDS patients. Although this drug is commonly well tolerated and rarely causes severe lung injury, it is important to consider the potentially serious adverse effects of azacitidine-induced pneumonitis.
Assuntos
Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Pneumonia/induzido quimicamente , Corticosteroides/uso terapêutico , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Humanos , Japão , Masculino , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Resultado do TratamentoRESUMO
We present the case of a 53-year-old woman who was employed at a mushroom (Pleurotus eryngii and Hypsizigus marumoreus) cultivation factory for 15 years. She was admitted to our hospital because of fever and dry cough. Chest radiography and CT scanning revealed diffuse ground glass opacity and centrilobular nodules in both lung fields. Serum KL-6 was elevated. In the bronchoalveolar lavage fluid, the CD4/CD8 ratio was reduced, and the lymphocyte fraction was very high. Transbronchial lung biopsy specimens showed lymphocyte alveolitis. After admission, the patient's symptoms improved rapidly without medication. Although these findings are compatible with hypersensitivity pneumonitis, it was difficult to identify a causative antigen. Serum antibody against Trichosporon was positive. A lymphocyte stimulation test of the peripheral blood was positive against extracts of P. eryngii and H. marumoreus. Furthermore, precipitins against the extracts of H. marumoreus were detected by a double immunodiffusion test. Therefore, we decided to conduct a challenge test using H. marumoreus. As an inhalation provocation test with H. marumoreus conducted in a sickroom caused the same clinical symptoms and signs as experienced in the workplace, we diagnosed hypersensitivity pneumonitis caused by H. marumoreus. A provocation test, in which antigen exposure is limited using a closed space, such as a sickroom, was simple, safe and effective for determining the antigen causing hypersensitivity pneumonitis.
Assuntos
Agaricales/imunologia , Alveolite Alérgica Extrínseca/etiologia , Doenças dos Trabalhadores Agrícolas/etiologia , Doenças dos Trabalhadores Agrícolas/imunologia , Alveolite Alérgica Extrínseca/imunologia , Testes de Provocação Brônquica , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A 52-year-old man had been treated by hemodialysis because of IgA nephropathy since 1994. Gastric MALT lymphoma was diagnosed in January 2007. Radiation therapy was performed for 4 weeks (40Gy) and the response was complete remission (CR) by September 2007. He was admitted to our hospital in February 2008 because of an abnormal chest shadow. Chest CT showed multiple cystic lesions with calcification and consolidation. Transbronchial lung biopsy from the area of consolidation (left S5) showed pulmonary invasion of small lymphoid cells. PCR analysis showed clonal rearrangement of the heavy chain of the immunoglobulin gene. Accordingly, MALT lymphoma was diagnosed. Rituximab infusion was performed, because CD20 immunostaining was positive and he had been treated by hemodialysis. The abnormal chest shadow was presented since gastric MALT lymphoma was diagnosed. We considered that MALT lymphoma occurred simultaneously in the stomach and lung.
Assuntos
Neoplasias Pulmonares/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Gástricas/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We reported a case of lung adenocarcinoma of Pancoast type that was successfully treated with chemoradiotherapy. A 66-year-old man was admitted to our hospital because of back pain. Chest computed tomography (CT) showed a Pancoast tumor on the left side. Using transbronchial needle aspiration, we diagnosed lung adenocarcinoma (cT3N0M0). The patient received chemoradiotherapy simultaneously(carboplatin AUC5 and irinotecan 60 mg/m2). There are no findings of tumor recurrence 8 years after chemoradiotherapy. This patient was successfully treated with concurrent chemoradiotherapy, which is suggested to be a useful therapy for Pancoast tumor.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome de Pancoast/tratamento farmacológico , Síndrome de Pancoast/radioterapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Terapia Combinada , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome de Pancoast/diagnóstico por imagem , Síndrome de Pancoast/patologia , Indução de Remissão , Tomografia Computadorizada por Raios XRESUMO
UNLABELLED: To assess the effects of usual interstitial pneumonia (UIP) and smoking in rheumatoid arthritis (RA) patients regarding lung cancer risk, we studied 86 RA patients (14 patients with lung cancer, 58 patients with UIP (RA/ UIP), and 14 patients with both). Among the 28 RA patients with lung cancer, 14 patients (50%) had UIP. Compared to the lung cancer patients without UIP, the proportion of smokers (92.6 vs 50%, p = 0.0328) and total pack-years of smoking (57.1 +/- 37.1 vs 19.5 +/- 21.9, p = 0.003) were significantly higher in lung cancer patients with UIP. There was no significant difference in age, sex, and histological type and location of lung cancer between these two groups. Among the 72 RA/UIP patients, 14 patients (19.4%) had lung cancer. Compared to RA/UIP-only patients, the proportion of smokers (92.6 vs 46.6%, p = 0.002) and total pack-years of smoking (57.1 +/- 37.1 vs 25.4 37.4, p = 0.006) were significantly higher in RA/UIP patients with lung cancer. There was no significant difference in age, sex, and the duration of RA between these two groups. The odds ratio of smoking and total pack-years of smoking over 20 for the development of lung cancer in RA/UIP patients were 14.93 and 21.27, and the differences were statistically significant (p = 0.002 and p < 0.001, respectively). CONCLUSION: 50% of RA patients with lung cancer had RA/UIP and 19.4% of RA/UIP patients had lung cancer. These findings suggest that RA/UIP may be associated with increased risk of development of lung cancer in RA patients. In an RA cohort study to assess the development of lung cancer, RA patients should be divided into two groups, one with RA/UIP and another without RA/UIP. Smokers with RA/UIP should be recommended to cease smoking.
Assuntos
Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/etiologia , Fumar/efeitos adversos , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco , Fatores de Risco , Fumar/epidemiologia , Abandono do Hábito de FumarRESUMO
We studied 149 rheumatoid arthritis (RA) patients (mean age 68.0 years; 68 men, 81 women) with pulmonary infections. The mean age at the onset of RA and the duration of RA was 57.2 +/- 15.2 years and 10.9 +/- 11.5 years, respectively. Pulmonary infections included nontuberculous mycobacteriosis in 59 patients (Mycobacterium avium complex infection, 50 cases : Mycobacterium kansasii infection, 4 cases; others, 5 cases), pneumonia in 46 patients, pulmonary tuberculosis in 28 patients, pulmonary aspergillosis in 12 patients, pulmonary cryptococcosis in 5 patients, Pneumocystis jiroveci pneumonia in 5 patients, lung abscess in 9 patients, exacerbation of bronchiectasis in 7 patients, and empyema in 4 patients. One hundred percent of patients with exacerbation of bronchiectasis, 91.7% of patients with pulmonary aspergillosis, 87% of patients with pneumonia, and 81.4% of patients with nontuberculous mycobacteriosis had underlying lung diseases. The pulmonary infections during therapy with steroids were pulmonary tuberculosis (78.6%), pneumonia (65.2%), and pulmonary aspergillosis (58.3%), while the pulmonary infections during methotrexate treatment were Pneumocystis jiroveci pneumonia (80%), pulmonary cryptococcosis (40%), and pulmonary tuberculosis (28.6%). Pulmonary infections in RA patients who were taking TNFalpha inhibitors included 1 patient each with nontuberculous mycobacteriosis, pneumonia, pulmonary tuberculosis, and Pneumocystis jiroveci pneumonia. Among the RA patients with lung abscess, malignancy was noted in 55.6%, and diabetes mellitus in 22.2%. Pseudomonas aeruginosa was the second-most-common cause of pneumonia and cause of all exacerbations of bronchiectasis. As well as immunosuppressive medications (steroids, methotrexate, TNFalpha inhibitors) and systemic comorbid diseases, underlying lung diseases could be one of the risk factor for pulmonary infections in patients with RA. The dominant risk factor for each pulmonary infection in patients with RA might be different.