Two case reports of rare antisynthetase syndrome and literature review / 中华风湿病学杂志

Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.

Construction of Question Prompt List of information needs of patients with interstitial lung disease based on ERG theory / 中国实用护理杂志

Objective:To construct a Question Prompt List of information needs for patients with interstitial lung disease, providing a tool for patients with interstitial lung disease to actively obtain disease-related information.Methods:A literature study was conducted based on the three core needs (ERG) theory framework of existence,relatedness and growth. A purposive sampling method was used to select 15 patients with interstitial lung disease from Drum Tower Hospital, Medical School of Nanjing University from December 2021 to January 2022 for descriptive research. Based on literature research and qualitative research, the initial items of the Question Prompt List were determined through expert inquiry, and the items were extracted, discussed, and adjusted, and finalized the list of information needs and prompts for patients with interstitial lung disease.Results:The 19 experts participated in the consultation, with a positive coefficient of 100.0% and 94.7% for two rounds of consultation, an authoritative coefficient of 0.91 and 0.92, and the Kendall coordination coefficient of 0.31 and 0.23, respectively. Finally, a list of interstitial lung disease patients′ question prompts containing 4 primary indicators and 34 secondary indicators was formed.Conclusions:Based on the ERG theory, the research method for the Question Prompt List of information needs for patients with interstitial lung disease is scientific and reliable, and can be used in clinical practice to help patients inquire and obtain the necessary information.

Fibroelastosis pleuroparenquimatosa e hipertension pulmonar: un fenotipo diferente?

La fibroelastosis pleuroparenquimatosa es una enfermedad pulmonar inusual con características clínicas, radiológicas y patológicas únicas, que se ha incluido recientemente en el consenso actualizado sobre neumonías intersticiales idiopáticas. Su nombre hace referencia a una combinación de fibrosis que involucra la pleura visceral y cambios fibroelastóticos que predominan en el parénquima pulmonar subpleural. Aunque se han descrito varias asociaciones de enfermedades, no se ha identificado de manera inequívoca ninguna causa única. El diagnóstico se sustenta en criterios clínicos-radiológicos y de hallazgos histopatológicos cuando se dispone de biopsias. Son escasos los reportes sobre la asociación entre esta entidad y la hipertensión pulmonar. No existe tratamiento hasta la fecha, aunque se relatan sucesos en algunos casos de transplante pulmonar. Describimos las características clínicas de un paciente atendido en un hospital del Paraguay.

Pleuroparenchymal fibroelastosis is an unusual lung disease with unique clinical, radiological, and pathological characteristics that has recently been included in the updated consensus on idiopathic interstitial pneumonia. Their name refers to a combination of fibrosis involving the visceral pleura and fibro-elastic changes that predominate in the subpleural pulmonary parenchyma. Although several associations between diseases have been described, no single cause has been unequivocally identified. The diagnosis is based on clinical-radiological criteria and histopathological findings when biopsies are available. There are few reports on the association between this entity and pulmonary hypertension. There is no treatment to date, although some cases of lung transplantation have been successful. We describe the clinical characteristics of a patient treated in a hospital in Paraguay.

Estudio de sobrevida a largo plazo en pacientes adultos con enfermedades respiratorias crónicas atendidos por infección respiratoria aguda por coronavirus SARS-CoV-2 / Study of long-term survival in adult patients with chronic respiratory diseases treated for acute respiratory infection by coronavirus SARS-CoV-2

La enfermedad respiratoria aguda por coronavirus SARS-CoV-2 (COVID-19) se ha convertido en un grave problema de salud pública a nivel mundial. Objetivos: Examinar el uso de recursos sanitarios, riesgo de complicaciones y muerte en pacientes adultos con enfermedades respiratorias crónicas atendidos por COVID-19. Métodos: Estudio clínico descriptivo prospectivo realizado en pacientes adultos atendidos por COVID-19 en la Red de Salud UC Christus entre el 1 de abril y 31 de diciembre de 2020. Resultados: Se evaluaron 2.160 pacientes adultos, edad: 47 ± 17 años (rango: 18-100), 51,3% sexo masculino, 43,8% tenía comorbilidades, especialmente hipertensión (23,2%), diabetes (11,7%) y enfermedades respiratorias crónicas: asma (5%), EPOC (1,4%) y enfermedad pulmonar difusa (EPD: 0,8%). Los pacientes adultos con enfermedades respiratorias crónicas tuvieron mayor riesgo de hospitalización y uso de oxígeno suplementario; sin embargo, la evolución de los pacientes asmáticos y la sobrevida a los doce meses fue similar a los pacientes sin comorbilidades atendidos por COVID-19, mientras que en los pacientes con EPOC y EPD la admisión a la unidad de paciente crítico y riesgo de muerte fueron más elevados. En el análisis multivariado, los principales predictores clínicos asociados al riesgo de muerte en el seguimiento a doce meses en pacientes adultos con COVID-19 fueron la edad y admisión al hospital, mientras que el asma fue un factor protector. Conclusión: Los pacientes asmáticos tuvieron bajo riesgo de complicaciones y muerte asociados a COVID-19; mientras que los pacientes con EPOC y EPD tuvieron mayor riesgo de complicaciones y muerte en el seguimiento a largo plazo.

The acute respiratory disease associated to coronavirus SARS-CoV-2 (COVID-19) has become a serious public health problem worldwide. Objectives: To examine the use of healthcare resources, risk of complications and death in adult patients with chronic respiratory diseases treated for COVID-19. Methods: Prospective descriptive clinical study conducted in adult patients treated for COVID-19 in the UC Christus Healthcare Network between April 1 and December 31, 2020. Results: 2,160 adult patients were evaluated, age: 47 ± 17 years-old (range: 18-100), 51.3% male, 43.8% had comorbidities, especially hypertension (23.2%), diabetes (11.7%), and chronic respiratory diseases: asthma (5%), COPD (1,4%) and interstitial lung disease (ILD: 0.8%). Adult patients with chronic respiratory diseases were at higher risk for hospitalization and use of supplemental oxygen; however, the evolution of asthmatic patients and survival at twelve months was similar to that of adult patients without comorbidities treated for COVID-19, while in patients with COPD and ILD admission to the critical care unit and risk of death were higher. In the multivariate analysis, the main clinical predictors associated to 12-month mortality risk in adult patients with COVID-19 were age and hospital admission, while asthma was a protective factor. Conclusion: Asthmatic patients had minor risk of complications and mortality associated with COVID-19; while patients with COPD and ILD had a significant higher risk of complications and 12-month mortality.

Clinical characteristics of idiopathic inflammatory myopathy patients with positive anti-melanoma differentiation-associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the clinical characteristics and prognosis of idiopathic inflammatory myopathy (IIM) patients with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:A total of 194 hospitalized IIM patients who were tested for myositis-specific autoantibodies (MSAs) in the Departments of Rheumatology and Immunology of Tianjin Medical University General Hospital from January 2015 to September 2020 were collected, including 29 cases with positive anti-MDA5 antibody and 165 cases with negative anti-MDA5 antibody. Their clinical data were analyzed retrospectively. T test was used for measurement data with normal distribution. Measurement data with non-normal distribution were tested by Mann-Whitney U rank sum test. χ2 test was used for counting data. Risk factors were analyzed by binary Logistic regression, survival analysis by Kaplan-Meier method and Cox regression analysis. Results:IIM patients with positive anti-MDA5 antibody had a high incidence of dermatomyositis specific skin rash, and the skin rash was the most common presenting symptom. In the positive anti-MDA5 antibody group, muscle symptoms were mild; and the patients were prone to have fever, arthritis, oral ulcer and weight loss. All patients were complicated with interstitial lung disease (ILD). In patients with negative anti-MDA5 antibody, white blood cell (WBC) count [7.59(5.61, 9.89)×10 9/L vs 4.07(3.17, 5.50×10 9/L, Z=-5.05, P<0.001], platelet (PLT) [249.00 (200.00, 302.00)×10 9/L vs 205.00 (178.00, 244.00)×10 9/L, Z=-2.59, P=0.010], lymphocyte (LY) [1.34(0.85, 1.94)×10 9/L vs 0.64(0.40, 0.83)×10 9/L, Z=-5.78, P<0.001), serum creatine kinase (CK) [558.00 (72.00, 2 959.00) U/L vs 64.00 (35.00, 149.50) U/L, Z=-3.97, P<0.001], creatine kinase isoenzymes (CK-MB) [38.00 (17.00, 127.00) U/L vs 16.00 (14.00, 25.00) U/L, Z=-3.84, P<0.001], myoglobin (MYO) [243.65 (60.50, 829.83) ng/ml vs 34.55(21.00, 104.23) ng/ml, Z=-3.98, P<0.001], troponin T (TnT) [0.09(0.03, 0.44) ng/ml vs 0.02(0.01, 0.04) ng/ml, Z=-4.17, P<0.001], albumin (ALB) [34.00(30.00, 38.00) g/L vs 31.00 (26.50, 36.00) g/L, Z=-2.68, P=0.007], cluster of differentiation 4 (CD4) + T cells [498.00(276.00, 752.00) cells/μl vs 259.50 (179.00, 498.25) cells/μl, Z=-2.79, P=0.005], partial pressure of carbon dioxide (PaCO 2) [39.00(36.13, 42.00) mmHg vs 35.35 (31.30, 38.88) mmHg, Z=-3.75, P<0.001], partial pressure of oxygen (PaO 2) [82.00(71.90, 90.20) mmHg vs 73.25(64.30, 84.05) mmHg, Z=-2.08, P=0.037], arterial oxygen saturation (SaO 2) [96.50% (95.05%, 97.30)% vs 95.80%(93.70%, 96.55%), Z=-2.11, P=0.035], diffusion capacity for carbon monoxide of the Lung (DLco) [(63±21) % vs (52±14)%, t=0.96, P=0.006] were significantly reduced, while UTP [260.50 (172.25, 401.25) g vs 331.00 (252.75, 666.25) g, Z=-2.18, P=0.029], alanine aminotransferase (ALT) [40.00 (21.00, 83.00) U/L vs 56.00(40.00, 107.50), Z=-2.27, P=0.023], glutamyltranspeptidas (GGT) [22.50(15.00, 42.00) U/L vs 57.00 (38.00, 101.50) U/L, Z=-4.98, P<0.001], D-Dimer [850.00 (485.00, 1 799.50) ng/ml vs 1 346.00 (896.50, 2 527.00) ng/ml, Z=-2.55, P=0.011], immunoglobulin (Ig)E [60.00 (25.60, 147.50) U/ml vs 173.00(68.25, 471.50) U/ml, Z=-3.06, P=0.002], C4[20.25(16.68, 25.03) mg/L vs 23.60(20.20, 28.35) mg/L, Z=-2.38, P=0.017], Fer [228.01 (115.40, 513.36) ng/ml vs 1 636.39 (851.80, 3 888.82) ng/ml, Z=-6.01, P<0.001], krebsvondenlungen-6 (KL-6) [365.00 (180.25, 1 018.75) U/ml vs 788.00 (406.00, 1 364.00) U/ml, Z=-2.10, P=0.035] were higher when compared to patients with positive anti-MDA5 antibody. In the anti-MDA5 antibody positive group, patients had high mortality rate [8.5%(14/165) vs 34.5%(10/29), χ2=13.07, P<0.001], and the use of intravenous immunoglobulin [32.7%(54/165) vs 65.5%(19/29), χ2=11.30, P=0.001] and steroid pulse therapy [4.8%(86/165) vs 27.6%(8/29), χ2=13.98, P<0.001] were more frequent. Patients in the positive anti-MDA5 antibody group were classified into two sub groups based on lung features: the rapidly progressive interstitial lung disease (RP-ILD) group (48.28%, 14/29) and the chronic interstitial lung disease (C-ILD) group (51.72%, 15/29). RP-ILD patients had significantly elder disease onset age, higher C-reaction protein (CRP), Fer, IgE levels and the positive rate of anti-Ro52 antibody, while ALT was lower. The difference was statistically significant. Regression analysis suggested that older onset age [ HR (95% CI)=1.154 (1.069, 1.246), P<0.001], male [ HR(95% CI)=6.383(1.038, 39.242), P=0.045], positive anti-MDA5 antibody [ HR(95% CI)=17.180 (2.900, 101.766), P=0.002], LY decrease [ HR (95% CI)=0.083 (0.008, 0.817), P=0.033], high serum Fer level [ HR (95% CI)=1.001(1.000, 1.001), P=0.016], increased D-Dimer [ HR(95% CI)=1.000(1.000, 1.001), P=0.004] and compicated with carcinoma [ HR (95% CI)=11.849 (1.978, 70.970), P=0.007] were independent risk factors for death in IIM patients. Binary logistic regression analysis suggested that late onset age [ OR(95% CI)=1.090 (1.005, 1.183), P=0.038], high Fer level [ OR (95% CI)=1.001 (1.000, 1.001), P=0.022] and decreased ALB [ OR (95% CI)=0.818 (0.696, 0.963), P=0.016] might be risk factors for RP-ILD in patients with positive anti-MDA5 antibody. Conclusion:In patients with positive anti-MDA5 antibody group, typical skin damage, mild muscle symptoms, high proportion of ILD and poor prognosis are chardcteristic when compared to patients without this autoantibody. It is necessary to monitor the disease activity closely and explore the treatment strategy.

Prognostic value of tumor markers in idiopathic inflammatory myopathy associated interstitial lung disease / 中华健康管理学杂志

Objective:To explore the correlation between tumor markers and prognosis of patients with idiopathic inflammatory myopathy (IIM) associated interstitial lung disease (ILD).Methods:A total of 149 patients who were no less than 18 years old and diagnosed with IIM-ILD from July 2017 to September 2019 in the First Affiliated Hospital of Zhengzhou University were consecutively enrolled in the study. Ten patients were lost to follow-up. The remaining 139 cases were regarded as research objects. Patients were divided into survival group or death group according to their one-year survival status. Then their baseline characteristics were compared. Univariate Cox regression analyses of age, gender, cancer, inflammatory indexes, muscle zymogram, tumor markers, ferritin, melanoma differentiation-associated gene 5 (MDA5) antibody and treatment regimens were conducted to identify prognostic risk factors of one-year mortality. Corrected multivariable cox regression was applied to screen the independent risk factors associated with one-year mortality of IIM-ILD. According to the cut-off value of carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) (6 μg/L and 28 μg/L, respectively), patients were divided into high-level groups and low-level groups. Kaplan Meier survival curve were generated to compare one-year survival rate of high-level groups and low-level groups. On the basis of qualitative results of MDA5 antibody, patients were split into two groups with positive MDA5 antibody or negative MDA5 antibody. The differences of CEA, NSE levels between the two groups and the correlation between CEA, NSE levels and ferritin were analyzed.Results:Age, lactate dehydrogenase (LDH), CEA, carbohydrate antigen (CA) 199, NSE and ferritin in the death group were higher than those in the survival group, while the rate of immunosuppressant administration was lower than that in survival group ( P<0.05). Univariate regression analyses showed that CEA, cytokeratin 19 fragment (CYFRA211) and NSE were risk factors for one-year mortality of IIM-ILD. Adjusted by age, treatment regimens and tumor, multivariate regression analysis showed that CEA [ HR=1.112, 95% CI (1.017-1.214), P=0.019] and NSE [ HR=1.033, 95% CI (1.002-1.064), P=0.034] were independent risk factors for one-year mortality. One-year survival rate of the group with CEA≥6 μg/L was lower than that in the group with CEA<6 μg/L (Logrank test, P<0.001). Similarly, one-year survival rate of the group with NSE≥28 μg/L was lower than that in the group with NSE<28 μg/L (Logrank test, P<0.001). In addition, the CEA level in patients with positive MDA5 antibody was higher than that in patients with negative MDA5 antibody ( P<0.001). However, there was no correlation between NSE and MDA5 antibody. Moreover, serum levels of CEA ( r=0.299, P=0.002) and NSE ( r=0.349, P<0.001) were positively correlated with ferritin. Conclusions:Tumor markers have predictive value for the prognosis of IIM-ILD. Higher CEA and NSE are independent risk factors for poor prognosis in patients with IIM-ILD.

Clinical characteristics and risk factors for mortality analysis of 94 cases of rheumatic diseases with pneumomediastinum / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors of rheumatic diseases complicated with Pneumomediastinum (PnM).Methods:A retrospective analysis of 94 inpatients with rheumatic diseases associated PnM from Peking Union Medical College Hospital and Shanxi Bethune Hospital between January 1998 and October 2018 was carried out. Patients were divided into idiopathic inflammatory myopathies (IIM) and the non-IIM group. Clinical features, laboratory examinations and treatment were compared between the two groups. Cox proportional hazard model was used to investigate the risk factors for prognosis.Results:A total of 94 patients were included in the study, with an average age of (45±14) years. Forty-five (48%) of them were male. There were 62 patients in the IIM group and the other 32 were in the non-IIM group. Sixty-nine patients had predisposing factors before PnM. Severe cough and assisted mechanical ventilation were the most common causes. Compared with the non-IIM group, the incidence of digital vasculitis (29% vs 6%, χ2=6.540, P=0.008), arthritis (60% vs 28%, χ2=8.409, P=0.004), interstitial lung disease (ILD)(98% vs 78%, χ2=11.129, P=0.002) were higher in the IIM group, treatment with cyclophosphamide was higher in the IIM group ( χ2=4.458, P=0.035). There was non-significant difference in mortality between the two groups during hospitalization (50% vs 59%) and 6 months after PnM (64% vs72%) ( P>0.05). Pulmonary infection was the only risk factor for poor prognosis [ HR=3.131, 95% CI (1.025, 9.561), P=0.045], in which bacteria infection was the most common cause (65/75, 86.7%). Conclusion:PnM is a severe complication of rheumatic diseases. To get a good prognosis, rheumatol-ogists should balance the benefit and risk of infection of immunosuppressive therapy.

The correlation between serum krebs von den lungen-6 level and immune function in rheumatoid arthritis patients with interstitial lung disease / 中华风湿病学杂志

Objective:To explore the correlation between serum krebs von den lungen-6 (KL-6) level and immune function in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD), and provide theoretical basis for clinical diagnosis and treatment.Methods:Eighty-six RA patients were divided into Non-RA-ILD group and RA-ILD group. The serum KL-6 level and immune function (the number of CD3 +, CD4 +, CD8 + and CD4 +/CD8 + ratio) of all subjects were detected. The correlation between serum KL-6) level and immune function was analyzed. The correlation analysis was performed by Pearson or Spearman rank correlation analysis. Results:There were 54 cases of Non-RA-ILD patients and 32 cases of RA-ILD patients in this study. The clinical data showed that RA-ILD patients were mainly male, and the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) were significantly increased( t=6.382, 7.243 and 7.748, P<0.05). The KL-6 level of RA-ILD patients [(835±72) U/ml] was significantly higher than that of Non-RA-ILD patients [(434±45) U/ml]. And the difference was statistically significant( t=31.670, P<0.05). Meanwhile, the number of CD8 + lymphocyte and CD4 +/CD8 + ratio of RA-ILD patients were significantly increased ( t=3.456 and 4.993, P<0.05). The results of correlation analysis showed that the level of KL-6 in serum was negatively correlated with the level of Ts cells CD8 + ( r=-3.563, P=0.031), and positively correlated with the ratio of CD4 +/CD8 + ( r=4.879, P=0.011). Conclusion:The level of serum KL-6 level is closely related to the abnormal immune function of RA-ILD patients. The serum KL-6 level can be used as an important index to evaluate the immune status of RA-ILD patients.

Difference in clinical characteristics of patients with primary Sj?gren's syndrome by gender and age of disease onset / 中华风湿病学杂志

Objective:To compare the clinical characteristics of patients with primary Sj?gren's syndrome (pSS) by gender and age of disease onset.Methods:Clinical data of hospitalized patients with pSS in China-Japan Friendship Hospital from March 2014 to August 2020 were retrospectively analyzed. Patients were divided into different groups according to their genders and ages of disease onset (young grong <30 years, middle-age group 30-59 years, elderly group ≥60 years). Chi-square test and Mann-Whitney U test were used to compare data in subgroups, and logistic regression was performed to analyze data after control covariates. Results:Five hundred and forty one patients with pSS were included in this study and 481 of them were women (88.9%) Women had higher ratio than men in dry mouth [ OR (95% CI) =2.172(1.091, 4.323), P=0.027], dry eyes [ OR(95% CI)=2.179(1.062, 4.469), P=0.034], leukocytopenia [ OR(95% CI)=3.789(1.150, 12.482), P=0.029], ANA titer≥1∶160 [ OR(95% CI)=2.233(1.279, 3.898), P<0.01], positive anti-SSA [ OR(95% CI)=2.919(1.644, 5.183), P<0.01], positive anti-Ro52 [ OR(95% CI)=3.018(1.685, 5.405), P<0.01], while men had higher ratio than women in parotid enlargement [ OR(95% CI)=2.345(1.281, 4.325), P<0.01], and interstitial lung disease (ILD) [ OR(95% CI)=2.593(1.460, 4.606), P<0.01]. Compared with patients in young group, patients in middles age group had higher ratio in dental caries [ OR(95% CI)=5.940(2.230, 15.819), P<0.01], xero-phthalmia [ OR(95% CI)=2.904(1.313, 6.425), P<0.01], arthralgia [ OR(95% CI)=1.959(1.039, 3.694), P=0.038] and ILD [ OR(95% CI)=2.247(1.018, 4.959), P=0.045], but lower ratio in renal involvement [ OR(95% CI)=0.402(0.211, 0.766), P<0.01]; patients in elderly group had higher ratio in dental caries [ OR(95% CI)=7.437(2.441, 22.656), P<0.01], xerophthalmia [ OR(95% CI)=6.084(1.901, 19.468), P<0.01], and ILD [ OR(95% CI)=4.857(2.029,11.627), P<0.01]. Compared with patients in elderly group, patients in young group had higher positive rate in anti-SSA [ OR(95% CI)=2.836(1.245, 6.459), P=0.013], anti-SSB [ OR(95% CI)=3.075(1.413, 6.690), P<0.01], rheumatoid factors (RF) [ OR(95% CI)=3.323(1.620, 6.817), P<0.01] and elevated immunoglobulin G (IgG)[ OR(95% CI)=3.567(1.747, 7.284), P<0.01]; patients in middle age group had higher positive rate in anti-SSB[ OR(95% CI)=2.330(1.315, 4.130), P<0.01], RF [ OR(95% CI)=2.026(1.279, 3.208), P<0.01], and elevated IgG [ OR(95% CI)=2.077(1.297, 3.327), P<0.01]. Conclusion:Women with pSS present a higher ratio in dry mouth, dry eyes, leukocytopenia and positive autoantibodies than men, while parotid enlargement and ILD are more common in men than women. Young patients are prone to renal involvement, middle-aged patients are prone to arthralgia, while elderly patients are prone to dental caries and xerophthalmia. With the growth of age, the positive rates of autoantibodies and elevated IgG are decreased gradually in patients with pSS, but the ratios of dental caries, xerophthalmia and ILD is increased gradually.

Historia y metodología de las primeras guías chilenas de fibrosis pulmonar idiopática 2019 / History and methodology of the first Chilean idiopathic pulmonary fibrosis guidelines, 2019

Desde 2017 los miembros de la Comisión de Enfermedades Pulmonares Intersticiales Difusas de la Sociedad Chilena de Enfermedades Respiratorias hemos trabajado en la elaboración de las primeras guías de fibrosis pulmonar idiopática (FPI) del país, necesidad evidente para fomentar el diagnóstico precoz y adecuado de la enfermedad y establecer una base para posible incorporación de su cuidado en cobertura de seguros de salud especiales. Se elaboraron 5 preguntas de revisión de evidencia y el resto se trabajó en formato de preguntas de contexto. Un grupo de metodólogos graduaron la evidencia siguiendo la metodología GRADE.

Since 2017, the members of the Commission of Diffuse Interstitial Lung Diseases of the Chilean Society of Respiratory Diseases have worked in the development of the first guidelines of idiopathic pulmonary fibrosis (IPF) in the country, an obvious need to encourage early and adequate diagnosis of the disease and establish a basis for possible incorporation of IPF patients care into special health insurance coverage. Five evidence review questions were prepared and the remainder were worked out in context question format. A group of methodologists graduated the evidence following the GRADE methodology.

Enfermedades pulmonares intersticiales. Una perspectiva actual / Update on interstitial lung diseases

Interstitial lung diseases are a broad, diverse, challenging group of diseases, most of them chronic whose prognosis is not good. In the last two decades there have been considerable advances in the knowledge of the epidemiology, pathological and genetic bases and treatment of several of these diseases. This article summarizes and presents updated information about their classification, new knowledge on genetics and treatments in idiopathic pulmonary fibrosis, advances in the diagnosis and management of hypersensitivity pneumonitis and a review of the broad spectrum of interstitial diseases associated with connective tissue diseases. Several clinical trials are currently underway whose results will be available in the coming years and will provide more information and tools to improve the treatment of these patients.

Clinical analysis of anti-neutrophil cytoplasmic antibody associated vasculitis complicated with interstitial lung disease / 中华风湿病学杂志

Objective To investigate the clinical featuresand related factors of anti-neutrophil cytoplasmic antibody associated vasculitis (AVV) with interstitial lung disease (ILD),and to explore the highresolution computed tomography (HRCT) of the chest features between different anti-neutrophil cytoplasmic antibody (ANCA) serotypes.Methods Clinical date of 125 patients diagnosed with AAV by Tianjin Medical University General Hospital from January 1,2010 to April 30,2017 were analyzed retrospectively.Clinical manifestations between AAV patients with ILD or those without ILD (NILD) were compared.Patients who were complicated with ILD were divided into myeloperoxidase (MPO)-ANCA positive subset and proteimase (PR3)-ANCA positive subset,and the pulmonary computed tomographic mani-festation was compared among the two subsets.The count data was analyzed by t test,chi-square test/Fisher exact probality.Logistic regression model was applied to analyze the related factors.Results Of the 125 AAV patients,86 (68.8％) patients were complicated with inter-stitial lung disease,and the mean age of ILD subgroup was higher than that of the NILD subgroup [(66±11) years vs (56±15) years,t=-3.78,P=0.001].Com-pared with NILD patients,ILD patients had more symptoms (x2=4.676,P=0.031).The serum levels of carcinoe-mbryonic antigen (t=-1.908,P=0.012),carbohydrate antigen 19-9 (t=-2.286,P=0.025) and carbohydrate antigen 153 (t=-2.857,P=0.007) were higher than the NILD pa-tients.In addition,MPO-ANCA positivesubgroup was more likely to present with pulmonary fibrosis (x2=7.736,P=0.005),reticular shadow (x2=9.762,P=0.002) and honeycombing (x~=4.278,P=0.039)than PR3-ANCA positive subgroup on CT images of all ILD patients.Multivariate Logistic regressive analysis showed that patients who were older than 65 years [OR(95％CI):3.305(1.280,8.531),P=0.013],and Birmingham vasculitis activity(BVAS) score higher than or equal to 15 [OR(95％CI):3.249(1.280,8.247),P=0.013] were risk factors for AAV patients with ILD,while the probability of PR3-ANCA positive patients complicated with ILD was low [OR (95％CI):0.063 (0.005,0.851),P=0.037].Conclusion ILD is a very common clinical feature in AAV,especially for elders.The increase of serum CEA,CA199 and CA153 levels may be an early warning sign of interstitial lung disease.Pulmonary HRCT may more likely to present with pulmonary fibrosis in patients with MPO-ANCA positive.

Clinical analysis of anti-neutrophil cytoplasmic antibody associated vasculitis complicated with inter-stitial lung disease / 中华风湿病学杂志

Objective@#To investigate the clinical featuresand related factors of anti-neutrophil cytoplasmic antibody associated vasculitis (AVV) with interstitial lung disease (ILD), and to explore the high-resolution computed tomography (HRCT) of the chest features between different anti-neutrophil cytoplasmic antibody (ANCA) serotypes.@*Methods@#Clinical date of 125 patients diagnosed with AAV by Tianjin Medical University General Hospital from January 1, 2010 to April 30, 2017 were analyzed retrospectively. Clinical manifestations between AAV patients with ILD or those without ILD (NILD) were compared. Patients who were complicated with ILD were divided into myeloperoxidase (MPO)-ANCA positive subset and proteimase (PR3)-ANCA positive subset, and the pulmonary computed tomographic mani-festation was compared among the two subsets. The count data was analyzed by t test, chi-square test/Fisher exact probality. Logistic regression model was applied to analyze the related factors.@*Results@#Of the 125 AAV patients, 86(68.8%) patients were complicated with inter-stitial lung disease, and the mean age of ILD subgroup was higher than that of the NILD subgroup [(66±11) years vs (56±15) years, t=-3.78, P=0.001]. Com-pared with NILD patients, ILD patients had more symptoms (χ2=4.676, P=0.031). The serum levels of carcinoe-mbryonic antigen (t=-1.908, P=0.012), carbohydrate antigen 19-9 (t=-2.286, P=0.025) and carbohydrate antigen 153 (t=-2.857, P=0.007) were higher than the NILD pa-tients. In addition, MPO-ANCA positivesubgroup was more likely to present with pulmonary fibrosis (χ2=7.736, P=0.005), reticular shadow (χ2=9.762, P=0.002) and honeycombing (χ2=4.278, P=0.039) than PR3-ANCA positive subgroup on CT images of all ILD patients. Multivariate Logistic regressive analysis showed that patients who were older than 65 years [OR(95%CI): 3.305(1.280, 8.531), P=0.013], and Birmin-gham vasculitis activity(BVAS) score higher than or equal to 15 [OR(95%CI): 3.249(1.280, 8.247), P=0.013] were risk factors for AAV patients with ILD, while the probability of PR3-ANCA positive patients complicated with ILD was low [OR(95%CI): 0.063(0.005, 0.851), P=0.037].@*Conclusion@#ILD is a very common clinical feature in AAV, especially for elders. The increase of serum CEA, CA199 and CA153 levels may be an early warning sign of interstitial lung disease. Pulmonary HRCT may more likely to present with pulmonary fibrosis in patients with MPO-ANCA positive.

Multidisciplinary discussion for diagnosis of lung diseases: A retrospective analysis of 217 cases undergoing non-tumor lung biopsy / 中华老年医学杂志

Objective@#To study on the diagnostic value of non-tumor lung biopsy by the multidisciplinary discussion including clinician, radiologist and pathologist.@*Methods@#Clinical data, imaging data and data of hematoxylin-eosin, immunohistochemical and special staining of pathological lung tissues in 217 cases undergoing non-tumor lung biopsy in Beijing Hospital during July 2015 to July 2018 were retrospectively analyzed.The diagnosis results were summarized and analyzed.@*Results@#The age range in 217 cases was 45-89 years, and the median age was 67 years, with 92 females and 125 males.The descriptive diagnoses were found in forty-two cases(19.4%, 42/217). And 175 cases could be confirmatively diagnosed by the multidisciplinary discussion of clinician, radiologist and pathologist.And the diagnostic rate of lung puncture biopsy was 80.6%(175/217 cases). Inflammatory lesions were divided into infection and non-infection.A total of 68 infection cases(31.3%, 68/217)included tuberculosis(43/68, 63.2%), bacterial pneumonia(14/68, 20.6%)and fungal infection(11/68, 16.2%). A total of 107 cases(49.3%, 107/217)of non-infective cases included the following: organized pneumonia(53/107, 49.5%), interstitial pneumonia with autoimmune features(iPAF)(16/107, 15.0%), nonspecific interstitial pneumonia(NSIP)(13/107, 12.1%), hypersensitivity pneumonitis(8/107, 7.5%), granulomatosis with polyangiitis(GPA)(4/107, 3.7%), eosinophilic pneumonia(2/107, 1.9%), sarcoidosis(2/107, 1.9%), acute fibrinous and organizing pneumonia(AFOP)(2/107, 1.9%)and coal pneumoconiosis(2/107, 1.9%, for each), and IgG4 related diseases(1/107, 0.9%), pleuraparenchymal fibroelastomatosis(PPFE)(1/107, 0.9%), asbestos lung(1/107, 0.9%), lipid pneumonia(1/107, 0.9%)and inhaled pneumonia(1/107, 0.9%).@*Conclusions@#The diagnoses of the puzzled non-tumor lung diseases were more accurate by pathological examination of lung tissue by using special stain, immunohistochemical stain and other pathological means, and by close multidisciplinary consultation of clinician, radiologist and pathologist, so as to facilitate the diagnosis and treatment of diseases.

Multidisciplinary discussion for diagnosis of lung diseases: A retrospective analysis of 217 cases undergoing non-tumor lung biopsy / 中华老年医学杂志

Objective To study on the diagnostic value of non-tumor lung biopsy by the multidisciplinary discussion including clinician,radiologist and pathologist.Methods Clinical data,imaging data and data of hematoxylin-eosin,immunohistochemical and special staining of pathological lung tissues in 217 cases undergoing non-tumor lung biopsy in Beijing Hospital during July 2015 to July 2018 were retrospectively analyzed.The diagnosis results were summarized and analyzed.Results The age range in 217 cases was 45-89 years,and the median age was 67 years,with 92 females and 125 males.The descriptive diagnoses were found in forty-two cases(19.4％,42/217).And 175 cases could be confirmatively diagnosed by the multidisciplinary discussion of clinician,radiologist and pathologist.And the diagnostic rate of lung puncture biopsy was 80.6％ (175/217 cases).Inflammatory lesions were divided into infection and non infection.A total of 68 infection cases (31.3％,68/217) included tuberculosis (43/68,63.2％),bacterial pneumonia (14/68,20.6％) and fungal infection(11/68,16.2％).A total of 107 cases(49.3％,107/217)of non-infective cases included the following:organized pneumonia(53/107,49.5 ％),interstitial pneumonia with autoimmune features (iPAF) (16/107,15.0 ％),nonspecific interstitial pneumonia(NSIP) (13/107,12.1％),hypersensitivity pneumonitis(8/107,7.5％),granulomatosis with polyangiitis (GPA) (4/107,3.7％),eosinophilic pneumonia (2/107,1.9％),sarcoidosis (2/107,1.9％),acute fibrinous and organizing pneumonia (AFOP) (2/107,1.9 ％) and coal pneumoconiosis (2/107,1.9 ％,for each),and IgG4 related diseases (1/107,0.9％),pleuraparenchymal fibroelastomatosis (PPFE) (1/107,0.9％),asbestos lung(1/107,0.9％),lipid pneumonia(1/107,0.9％) and inhaled pneumonia(1/107,0.9％).Conclusions The diagnoses of the puzzled non-tumor lung diseases were more accurate by pathological examination of lung tissue by using special stain,immunohistochemical stain and other pathological means,and by close multidisciplinary consultation of clinician,radiologist and pathologist,so as to facilitate the diagnosis and treatment of diseases.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 5. Connective Tissue Disease Associated Interstitial Lung Disease / 결핵

Connective tissue disease (CTD) is a collection of disorders characterized by various signs and symptoms such as circulation of autoantibodies in the entire system causing damage to internal organs. Interstitial lung disease (ILD) which is associated with CTD is referred to as CTD-ILD. Patients diagnosed with ILD should be thoroughly examined for the co-occurrence of CTD, since the treatment procedures and prognosis of CTD-ILD are vary from those of idiopathic interstitial pneumonia. The representative types of CTD which may accompany ILD include rheumatoid arthritis, systemic sclerosis (SSc), Sjögren's syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematous. Of these, ILD most frequently co-exists with SSc. If an ILD is observed in the chest, high resolution computed tomography and specific diagnostic criteria for any type of CTD are met, then a diagnosis of CTD-ILD is made. It is challenging to conduct a properly designed randomized study on CTD-ILD, due to low incidence. Therefore, CTD-ILD treatment approach is yet to been established in absence of randomized controlled clinical trials, with the exception of SSc-ILD. When a patient is presented with acute CTD-ILD or if symptoms occur due to progression of the disease, steroid and immunosuppressive therapy are generally considered.

Association of human leucocyte antigen-DRB1 alleles and the development of anti-melanoma differentiation-associated gene 5 antibodies in patients with dermatomyositis / 中华风湿病学杂志

Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM).Methods Seventy patients with PM,104 patients with DM and 400 healthy controls were included.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued by enzyme linked immunosorbent assay using recombinant MDA5 antigen.The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test.Results Frequencies of DRB1 * 04∶01 [17.0％ vs 1.3％,corrected P-value (Pc)=3.8×10-8;odds ratio (OR)=16.2;95％ confidence interval (CI) (6.6,39.7)] and DRB1 * 12∶02 [(42.6％ vs 19.3％,Pc=0.008;OR=3.1;95％ CI(1.7,5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls.The frequencies of DRB1 * 04∶01 [P=5.2×10-6,OR=17.1,95％CI:(5.3,54.9)\ and * 12∶02 [P=3.8×10-4,OR=3.1,95％CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls,whereas the frequencies of DRB1 * 04∶01 and * 12∶02 did not differ between the anti-MDA5 negative DM-ILD patients and the controls.No difference in the frequency of DRB1 alleles,other than * 04∶01,carrying the shared epitope (SE),i.e.* 01∶01,* 01∶02,* 04∶05 and * 10∶01,was observed between the controls and DM patients stratified by the presence of anti-MDA5 and ILD.Conclusion DRB1 * 04∶01 and * 12∶02 confer susceptibility to anti-MDA5 antibody production in DM,which cannot be explained by the SE hypothesis.

Diagnostic value of clinical significance of serum chemokine-4 detection in patients with systemic sclerosis complicated with interstitial lung disease / 中华风湿病学杂志

Objective To investigate the clinical significance of serum chemokine-4 (CXCL-4) in systemic sclerosis (SSc) patients complicated with SSc-interstitial lung disease (SSc-ILD).Methods Sixty-two patients with SSc wbo met the new classification criteria of American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) SSc in 2013 and were treated by rheumatology department of Jiangxi Provincial People's Hospital from September 2015 to July 2017 were divided into the SSc combined with ILD group (30 cases) and simple SSc group (32 cases) according to the results of HRCT test,in reference to the 2013 American Thoracic Society/European Respiratory Society (ATS/ERS) ILD diagnostic criteria.A certain number of healthy subjects were selected as healthy control group (35 cases).Serum concentrations of CXCL-4 were determined by enzyme-linked immunosorbent assay (ELISA),and the difference of CXCL-4 concentration among the 3 groups were analyzed.All data were analyzed by t test,x2 test,rank-sum test and Logistic regressive analysis.Results The level of CXCL-4 in the SSc-ILD group [(133±17) ng/ml] was higher than that of the SSc group [(122±19) ng/ml] and normal control group [(115±19) ng/ml] (t=11.414,P=0.012;t=17.917,P=0.000);there was no significant difference between the SSc group and the normal control group (t=6.504,P=0.130);binary Logistic regression analysis found that the level of CXCL4 was positively correlated with ILD [P=0.019,OR=1.035,95％CI(1.006,1.066)].Conclusion Elevated levels of CXCL-4 in patients with SSc may be associated with concurrent ILD,CXCL-4 is expected to be a new serological marker for early diagnosis and evaluation of patients with SSc-ILD.It may be used as a sensitive indicator for evaluating the condition and prognosis of patients with SSc-ILD and provide a new target for clinical guidance of SSc-ILD therapy.

Genetic defect types associated with interstitial lung disease / 中华实用儿科临床杂志

Interstitial lung disease (ILD),also known as the diffuse parenchymal lung diseases(DPLD),are a heterogeneous group of the chronic respiratory disorders with various causes.The etiology of the ILD in infants includes the surfactant dysfunction and immunodeficiency,which are mainly caused by single gene defects or mutations.The common surfactant dysfunction is caused by the mutation of surfactant protein B gene (SFTPB),surfactant protein C gene (SFTPC),adenosine triphosphate binding cassette transport A3 (ABCA3)gene and thyroid transcription factor 1 gene,can presented as the deadly neonatal respiratory distress syndrome(RDS),and the ILD in the children.Gene mutation of the granulocyte-macrophage colony stimulating factor receptor can lead to hereditary pulmonary alveolar proteinosis (PAP),and mucins 5 B gene,telomerase reverse transcriptase gene,telomerase RNA component gene were associated with adult pulmonary fibrosis.In recent years,it has been found that the mutation of some immune genes,such as STING,GATA2 and STAT5,which can lead to interstitial lung disease of children.With the development of gene technology,the more etiology of gene in the interstitial lung disease are diagnosed by the new technology.

Characteristics and survival of connective tissue disease associated pulmonary arterial hypertension patients with and without interstitial lung disease / 中华风湿病学杂志

Objective To explore the characteristics and survival of connective tissue disease (CTD) patients with both of pulmonary arterial hypertension (PAH) arnd interstitial lung disease (ILD),and to compare with CTD patients with isolated PAH.Methods All adult CTD patients who visited one of the three referral centers in China with a diagnosis of PAH confirmed by right heart catheterization from July 2006 to May 2011 were enrolled.They were then divided into two groups (ILD with and without-ILD group) based on chest CT and then the comparison of baseline characteristics and survival at the endpoint of follow up were made between the two groups.T test,Mann-Whitney U test,x2 test,Kaplan-Meier survival analysis and Cox regression analysis were used for statistical analyses.Results One hundred and twenty-six patients were recruited into the study.Patients with ILD (n=27) were older than those without ILD (n=99).Lung function results including FVC [(75±18)％ vs (83±13)％,t=2.212,P=0.037] and DLCO [(54±22)％ vs (68±20)％,t=2.392,P=0.019] in ILD group were significantly wose than those without-ILD group.Although some important hemodynamic parameters such as mean pulmonary arterial pressure and pulmonary vascular resistance were better in the ILD group than the without-ILD group,Kaplan-Meier analysis showed that the short term survival of ILD group was significantly worse than that of the without-ILD group (72.7％ versus 94.7％ at 1 year and 63.6％ versus 81.1％ at 3 year,P=0.047).In ILD group,Cox regression analysis showed that SvO2 was the only independent factor for the short term survival [HR=0.19,95％CI (0.04,0.83),P=0.027],and Kaplan-Meier analysis showed patients with SvO2＜60％ had significantly lower short term survival than patients with SvO2 ≥60％ (1 and 2 year survival were 60.0％ and 40.0％ versus 92.9％ and 77.4％ respectively,P=0.002).Conclusion Patients with both PAH and ILD is a special subtype in CTD.Although with the superiority of hemodynamics,these patients have significantly worse survival than CTD patients with isolated PAH.Low SvO2 is the independent risk factor for the short term mortality in patients of CTD complicated by both PAH and ILD.More attention should be paid to these patients and the management strategy should be investigated further.