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1.
Clin Exp Rheumatol ; 37 Suppl 119(4): 115-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573469

RESUMO

OBJECTIVES: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%. Recently, nintedanib has been reported to exert anti-fibrotic activity on systemic sclerosis (scleroderma, SSc) skin fibroblasts and to diminish skin and lung fibrosis in mouse models. The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD). METHODS: Study was performed using lung fibroblasts (LF) isolated from five patients with SSc-ILD and from three control subjects. RESULTS: Nintedanib inhibited LF proliferation and migration in a concentration- and time-dependent manner. The proliferation rate of LF stimulated with PDGF in the presence of nintedanib was reduced 1.9-fold within 24 h as compared to cells stimulated with PDGF alone. Migration of SSc-ILD LF incubated with 100 nM nintedanib was reduced from 62.8±12.5% to 39.1±9.0% in the presence of PDGF and from 38.2±7.9% to 26.6±7.2% in serum-free medium. Nintedanib attenuated PDGF-induced Ca2+ efflux, reduced α-SMA promoter activity and α-SMA protein expression. Furthermore, nintedanib blocked PDGF-induced differentiation of normal LF to myofibroblasts, reduced production of collagen and fibronectin, and decreased contractility of SSc-ILD LF in both floating and fixed collagen gels. CONCLUSIONS: Our data demonstrate significant antifibrotic efficacy of nintedanib in SSc-ILD LF suggesting that nintedanib has the potential not only to prevent but also to reverse the increased activity of LF consequently attenuating excessive lung fibrosis observed in SSc-ILD.


Assuntos
Fibrose Pulmonar Idiopática , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais , Inibidores de Proteínas Quinases/uso terapêutico , Escleroderma Sistêmico , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Pulmão/citologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(9): 700-704, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31484245

RESUMO

Objective: To explore the effect of pirfenidone in fibrotic interstitial pneumonia with autoimmune features (IPAF) after treatment with corticosteroids and immunosuppressants. Methods: We conducted a retrospective analysis of 2 adult patients with IPAF in the Peking Union Medical College Hospital. As their fibrotic interstitial lung disease failed to improve with further treatment with corticosteroids and immunosuppressants, they were treated with pirfenidone based on corticosteroids and immunosuppressants. Their clinical, chest radiological data and prognosis were collected and relevant literatures were reviewed. Results: One patient was a 43 year old female, the other was a 53 year old male. IPAF was diagnosed with their classic clinical, serological and radiological features. They were partially responded to corticosteroids and immunosuppressants at the initial period. Pirfenidone was suggested for them as their lung fibrosis was not improved further with immunosuppressive therapy. After 4-5 months treatment with pirfenidone, based on corticosteroids and immunosuppressant administration, their clinical and radiological manifestations improved significantly. Conclusions: Pirfenidone might be a good add-on choice for fibrotic IPAF when the disease did not respond well to corticosteroids and immunosuppressants.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças Autoimunes/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Piridonas/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
J Photochem Photobiol B ; 197: 111510, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163288

RESUMO

Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa. The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy, Raman spectroscopy, FTIR, FESEM, HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa. A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells. The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases.


Assuntos
Antibacterianos/química , Ciprofloxacino/química , Portadores de Fármacos/síntese química , Lipídeos/química , Nanopartículas/química , Selênio/química , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Catalase/metabolismo , Ciprofloxacino/farmacologia , Ciprofloxacino/uso terapêutico , Portadores de Fármacos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Superóxido Dismutase/metabolismo
6.
N Engl J Med ; 380(26): 2518-2528, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31112379

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).


Assuntos
Inibidores Enzimáticos/uso terapêutico , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Escleroderma Sistêmico/complicações , Administração Oral , Adulto , Diarreia/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico , Capacidade Vital
7.
Autoimmun Rev ; 18(7): 658-664, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059843

RESUMO

Anti-OJ autoantibodies are rare myositis-specific autoantibodies that have been described to target isoleucyl-tRNA synthetase. Routinely used multiplex assays perform poorly in detection of anti-OJ antibodies. In this manuscript, we review the existing literature on critical issues in detection of anti-OJ and the clinical features associated with anti-OJ. The challenging detection with line/blot immunoassays and ELISAs is most likely related to the characteristics of the autoantigen involved, which is part of a multi-enzyme synthetase complex. Anti-OJ autoantibodies might therefore be more aptly termed anti-OJ complex autoantibodies. Anti-OJ autoantibodies are associated with the anti-synthetase syndrome, with interstitial lung disease (ILD) frequently being the sole manifestation. Myositis, present in the majority of patients with anti-OJ antibodies, is more severe than in patients with other anti-aminoacyl-tRNA synthetases. Most patients respond to glucocorticoid therapy. As detection of anti-OJ is relevant for treatment, reliable and practical detection is needed. Meanwhile, clinicians need to be aware of the possibility of anti-OJ in patients with ILD, isolated or in combination with myositis.


Assuntos
Autoanticorpos/imunologia , Isoleucina-tRNA Ligase/imunologia , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Miosite/tratamento farmacológico , Miosite/imunologia
8.
Pan Afr Med J ; 32: 40, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31143345

RESUMO

Anti-synthetase syndrome (ASS) is an inflammatory myopathy commonly associated with pulmonary involvement, especially parenchymal (diffuse infiltrative pneumonitis). Extrathoracic manifestations associated with pulmonary involvement can give an indication to the diagnosis: myalgias, polyarthralgias, Raynaud's syndrome, erythematous palmar hyperkeratosis with fissures and fever. Given the suggestive clinical and radiological picture, the presence of aminoacyl-transfer RNA (tRNA) synthetase antibodies enables to confirm, in particular, Anti Jo-1 antibody activity. Pulmonary involvement is a major prognostic factor, hence the indication for intensive immunosuppressive therapy based on corticosteroids, immunosuppressive medications or the association among them. A better awareness about this disorder revealed by pulmonary manifestations could enable early and adequate management and to improve patient's prognosis.


Assuntos
Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/etiologia , Miosite/diagnóstico , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Miosite/tratamento farmacológico , Miosite/imunologia , Prognóstico
9.
Eur Respir Rev ; 28(151)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30814139

RESUMO

Patients with certain types of fibrosing interstitial lung disease (ILD) are at risk of developing a progressive phenotype characterised by self-sustaining fibrosis, decline in lung function, worsening quality of life, and early mortality. It has been proposed that such progressive fibrosing ILDs, which show commonalities in clinical behaviour and in the pathogenetic mechanisms that drive progressive fibrosis, may be "lumped" together for the purposes of clinical research and, potentially, for treatment. At present, no drugs are approved for the treatment of ILDs other than nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis. For other progressive fibrosing ILDs, the mainstay of drug therapy is immunosuppression. However, it is postulated that, once the response to lung injury in fibrosing ILDs has reached the stage at which fibrosis has become progressive and self-sustaining, targeted antifibrotic therapy would be required to slow disease progression. Nintedanib, an intracellular inhibitor of tyrosine kinases, has shown antifibrotic, anti-inflammatory and vascular remodelling effects in several non-clinical models of fibrosis, irrespective of the trigger for the injury. Ongoing clinical trials will provide insight into the role of antifibrotic treatment with nintedanib or pirfenidone in the management of fibrosing ILDs with a progressive phenotype.


Assuntos
Doenças Pulmonares Intersticiais , Pulmão , Fibrose Pulmonar , Progressão da Doença , Nível de Saúde , Humanos , Indóis/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/fisiopatologia , Fenótipo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Piridonas/uso terapêutico , Qualidade de Vida , Fármacos do Sistema Respiratório/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(8): e14402, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813141

RESUMO

RATIONALE: Imatinib mesylate (imatinib) is a classic tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Although it is well tolerated by most patients and helps in the achievement of complete remission, a few rare imatinib-associated adverse effects such as pulmonary interstitial fibrosis have been reported. Because of its rareity, the clinical features of imatinib-induced interstitial lung disease (ILD) remain unclear. PATIENT CONCERNS: A 49-year-old Chinese man with chronic myeloid leukemia received oral treatment with imatinib and initially exhibited a good response. However, he presented with cough and fever 9 months after treatment initiation. DIAGNOSES: Pulmonary computed tomography indicated diffuse interstitial fibrosis in both lungs. All tests for possible infectious pathologies provided negative results. INTERVENTIONS: The patient was diagnosed with interstitial pneumonia and treated with antibiotics; however, there was no improvement. On the basis of a suspicion of imatinib-induced ILD, imatinib was discontinued and prednisone treatment was initiated. OUTCOMES: The patient's symptoms ameliorated with treatment, and imatinib was reintroduced. However, he developed cough and dyspnea again, and his treatment was switched to nilotinib as a second-line regimen. He was regularly monitored, and although his clinical symptoms ameliorated, computed tomography performed 29 months after he was diagnosed with ILD showed irreversible pulmonary interstitial fibrosis without progression. LESSONS: Clinicians should consider the possibility of severe irreversible ILD and carefully monitor patients receiving imatinib treatment.


Assuntos
Mesilato de Imatinib/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Tomografia Computadorizada por Raios X
13.
BMJ Case Rep ; 12(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739089

RESUMO

Panitumumab is a recombinant human IgG2 monoclonal antibody which is used for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or following FOLFIRI (fluoropyrimidine, oxaliplatin and irinotecan) containing chemotherapy regimen. We report a case of an 83-year-old Hispanic man, non-smoker, with KRAS/NRAS wild-type mCRC of the liver who was treated with 9 cycles of FOLFOX4 (fluorouracil, leucovorin and oxaliplatin) and cetuximab. Follow-up abdominal imaging showed progression of CRC, requiring initiation of panitumumab in addition to FOLFIRI. After 2 cycles of this combination chemotherapy, he presented with acute hypoxaemic respiratory failure. Pulmonary imaging showed new onset of interstitial lung disease (ILD). He was treated with systemic corticosteroids with marked improvement of ILD. We aim to highlight the risk of severe life-threatening ILD associated with panitumumab. Early recognition of this serious adverse event helps avoid unnecessary administration of systemic antibiotics and prevent mortality.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Panitumumabe/efeitos adversos , Adenocarcinoma/secundário , Corticosteroides/uso terapêutico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/patologia , Diagnóstico Precoce , Intervenção Médica Precoce , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/secundário , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Radiografia Torácica , Tomografia Computadorizada por Raios X
14.
BMC Cancer ; 19(1): 163, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30808322

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP. METHODS: We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016. RESULT: 31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2-14.0] vs. 10.0 [95% CI: 8.2-11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP. CONCLUSION: Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/mortalidade , Análise de Sobrevida , Resultado do Tratamento
15.
Arthritis Rheumatol ; 71(2): 182-195, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30604506
16.
J Photochem Photobiol B ; 191: 123-127, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30616036

RESUMO

Selinium nanoparticles (SeNPs) with minimal toxicity and efficient antioxidant properties were reported earlier for their anti-carcinogenic influence against various types of cancers, thus elevating its potential. In the present study, the anti-carcinogenic effect of selenium nanoparticles against lung cancer was studied. Selenium nanoparticles were biosynthesized and were characterized using UV- Vis absorption spectroscopy. A decrease in the absorption intensity was recorded with the increase in time, which represented the protein consumption during the reduction of SeO32- to Se0. The calculated average crystalline size from XRD studies of the synthesized selenium nanoparticles was found to be 88.89 nm which was in accordance with the TEM analysis while the SAED pattern has disclosed hexagonal ring structure with diffraction ring pattern.MTT assay was performed to evaluate the radio-sensitizing effect of selenium nanoparticles under the X-ray influence against cancer as well as healthy cell lines. SeNPs showed potent cytotoxicity effect in cancer cells whereas it showed relatively less toxic effect in normal healthy cells. However, caspase-3 activity was even more elevated when subjected to X-ray exposure than in the absence. These findings apparently revealed the cytotoxic potential of SeNPs + X-ray combination in the lung cancer cell lines.


Assuntos
Doenças Pulmonares Intersticiais/terapia , Neoplasias Pulmonares/terapia , Nanopartículas/química , Selênio/uso terapêutico , Antioxidantes/farmacologia , Caspase 3/metabolismo , Linhagem Celular , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/radioterapia , Neoplasias Pulmonares/radioterapia , Nanopartículas/uso terapêutico , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Raios X
17.
Zhonghua Er Ke Za Zhi ; 57(1): 21-26, 2019 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-30630227

RESUMO

Objective: To investigate the clinical features and outcomes of pulmonary surfactant protein C gene (SFTPC) 218 site mutation in children with pulmonary interstitial disease. Methods: In this retrospective study, the clinical data, outcomes and influencing factors of 7 cases of SFTPC gene 218 site mutations in infants with interstitial lung disease in three hospitals from January 2013 to December 2016 were analyzed. Results: Seven cases were full-term children, 4 cases had the onset within 3 months after birth, 2 cases after 1 year old, 1 case within 3 months to 1 year, clinical manifestations of these cases were cough, shortness of breath, dyspnea, and limited growth and development, could not maintain life without additional oxygen supplementation, blood gas analysis showed hypoxemia, 4 cases had clubbing. Chest CT showed diffuse ground glass-like change in both lungs. Three cases were positive for cytomegalovirus (CMV)-IgM or CMV-DNA. The mutations in 7 cases were exon 3, 5 of which were SFTPC gene c.218T>C, p.lle73Thr (heterozygous mutation), and 2 cases were SFTPC gene c.218T>A, p.lle73Asn (homozygous mutation), 1 case combined with ABCA3 gene mutations. Four patients were treated with prednisone alone, one with prednisone plus hydroxychloroquine, and two with symptomatic treatment. Three patients died, 3 patients improved, and 1 patient was lost to follow-up. Conclusions: The severity and prognosis of the children with SP-C 218 site mutation may be affected by many factors. Some children who received glucocorticoid alone do not have a good response.


Assuntos
Doenças Pulmonares Intersticiais , Proteína C Associada a Surfactante Pulmonar , Criança , Glucocorticoides/uso terapêutico , Humanos , Lactente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/genética , Mutação , Proteína C/genética , Proteína C Associada a Surfactante Pulmonar/genética , Surfactantes Pulmonares , Estudos Retrospectivos , Tensoativos , Resultado do Tratamento
18.
Tohoku J Exp Med ; 247(1): 51-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30674737

RESUMO

Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.


Assuntos
Corticosteroides/uso terapêutico , Ligas/efeitos adversos , Cobalto/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Profissionais/tratamento farmacológico , Doenças Profissionais/etiologia , Tungstênio/efeitos adversos , Idoso , Progressão da Doença , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Doenças Profissionais/diagnóstico por imagem , Radiografia Torácica
19.
Autoimmun Rev ; 18(2): 113-122, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572131

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD. METHODS: Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2 > 50%). RESULTS: Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5 ±â€¯5.5 years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5-93.6; 7 studies, n = 124) for corticosteroids alone, 80.7% (95%CI 49.6-94; 6 studies, n = 38) for cyclosporine A, 64.1% (95%CI 46.3-78.7; 4 studies, n = 32) for azathioprine, 86.2% (95%CI 61.5-96; 2 studies, n = 23) for tacrolimus, 56.4% (95%CI 44-68.0; 8 studies, n = 71) for cyclophosphamide, and 76.6% (95%CI 50.4-96.0; 2 studies, n = 20) for rituximab. In RP-ILD, survival rates at 3 months were 51.7% (95%CI 24.2-78.1; 2 studies, n = 11) for corticosteroids alone, 69.2% (95%CI 55.0-80.5; 8 studies, n = 146) for cyclosporine A and 72.4% (95%CI 6.4-99.0, 2 studies, n = 16) for cyclophosphamide. CONCLUSION: Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence.


Assuntos
Doenças Pulmonares Intersticiais/tratamento farmacológico , Miosite/tratamento farmacológico , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Miosite/etiologia , Miosite/patologia , Estudos Prospectivos
20.
Medicine (Baltimore) ; 97(49): e13542, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544464

RESUMO

The aim of this study was to evaluate whether serial measurements of serum Krebs von den Lungen-6 (KL-6) could be used to monitor disease activity and to detect recurrence in patients with interstitial pneumonia (IP) with anti-aminoacyl-tRNA synthetase antibodies (ARS-IP).This retrospective cohort study included 44 patients with ARS-IP. Thirty-six patients had serial data of blood tests and pulmonary function tests. Baseline and longitudinal analyses were performed to investigate whether lung function parameters were associated with serum biomarkers (KL-6, lactate dehydrogenase [LDH], and C-reactive protein [CRP]) using Pearson correlation coefficient. Additionally, the diagnostic accuracy of changes in these biomarkers for detecting ARS-IP recurrence was analyzed by receiver operating characteristic curve analysis.Baseline levels of serum KL-6 were significantly associated with vital capacity (VC) and diffusion capacity for carbon monoxide (DLco) (r = -0.40, P = .015, and r = -0.44, P = .010, respectively). Longitudinal changes in KL-6 were inversely correlated with changes in VC and DLco (r = -0.57, P <.001 and r = -0.42, P <.001, respectively), whereas those in LDH and CRP were not. Moreover, longitudinal changes in serum KL-6 were significantly associated with recurrence of ARS-IP and could be used to detect ARS-IP recurrence; the area under the curve was 0.79 (P = .002).The present study demonstrated that serial measurement of KL-6 is useful for monitoring disease activity and detecting recurrence of ARS-IP.


Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Doenças Pulmonares Intersticiais/sangue , Mucina-1/sangue , Adulto , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
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