Predictive factors for severe radiation-induced lung injury in patients with lung cancer and coexisting interstitial lung disease.

BACKGROUND AND PURPOSE: This study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. MATERIALS AND METHODS: The study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil-lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6-114) months. RESULTS: Among 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. CONCLUSION: Pretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI.

Automated CT quantification of interstitial lung abnormality and interstitial lung disease according to the Fleischner Society in patients with resectable lung cancer: prognostic significance.

OBJECTIVE: To assess the prognostic significance of automatically quantified interstitial lung abnormality (ILA) according to the definition by the Fleischner Society in patients with resectable non-small-cell lung cancer (NSCLC). METHODS: Patients who underwent lobectomy or pneumonectomy for NSCLC between January 2015 and December 2019 were retrospectively included. Preoperative CT scans were analyzed using the commercially available deep-learning-based automated quantification software for ILA. According to quantified results and the definition by the Fleischner Society and multidisciplinary discussion, patients were divided into normal, ILA, and interstitial lung disease (ILD) groups. RESULTS: Of the 1524 patients, 87 (5.7%) and 20 (1.3%) patients had ILA and ILD, respectively. Both ILA (HR, 1.81; 95% CI: 1.25-2.61; p = .002) and ILD (HR, 5.26; 95% CI: 2.99-9.24; p < .001) groups had poor recurrence-free survival (RFS). Overall survival (OS) decreased (HR 2.13 [95% CI: 1.27-3.58; p = .004] for the ILA group and 7.20 [95% CI: 3.80-13.62, p < .001] for the ILD group) as the disease severity increased. Both quantified fibrotic and non-fibrotic ILA components were associated with poor RFS (HR, 1.57; 95% CI: 1.12-2.21; p = .009; and HR, 1.11; 95% CI: 1.01-1.23; p = .03) and OS (HR, 1.59; 95% CI: 1.06-2.37; p = .02; and HR, 1.17; 95% CI: 1.03-1.33; and p = .01) in normal and ILA groups. CONCLUSIONS: The automated CT quantification of ILA based on the definition by the Fleischner Society predicts outcomes of patients with resectable lung cancer based on the disease category and quantified fibrotic and non-fibrotic ILA components. CLINICAL RELEVANCE STATEMENT: Quantitative CT assessment of ILA provides prognostic information for lung cancer patients after surgery, which can help in considering active surveillance for recurrence, especially in those with a larger extent of quantified ILA. KEY POINTS: • Of the 1524 patients with resectable lung cancer, 1417 (93.0%) patients were categorized as normal, 87 (5.7%) as interstitial lung abnormality (ILA), and 20 (1.3%) as interstitial lung disease (ILD). • Both ILA and ILD groups were associated with poor recurrence-free survival (hazard ratio [HR], 1.81, p = .002; HR, 5.26, p < .001, respectively) and overall survival (HR, 2.13; p = .004; HR, 7.20; p < .001). • Both quantified fibrotic and non-fibrotic ILA components were associated with recurrence-free survival and overall survival in normal and ILA groups.

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 and Radiological Features of Interstitial Lung Diseases Associated with Polymyositis and Dermatomyositis.

Polymyositis and dermatomyositis are autoimmune idiopathic systemic inflammatory diseases, characterized by various degrees of muscle inflammation and typical cutaneous lesions-the latter found in dermatomyositis. The underlying pathogenesis is characterized by a high level of uncertainty, and recent studies suggest diseases may have different immunopathological mechanisms. In polymyositis, components of the cellular immune system are involved, whereas in dermatomyositis, the pathogenesis is mainly mediated by the humoral immune response. The interstitial lung disease occurs in one-third of polymyositis and dermatomyositis patients associated with worse outcomes, showing an estimated excess mortality rate of around 40%. Lung involvement may also appear, such as a complication of muscle weakness, mainly represented by aspiration pneumonia or respiratory insufficiency. The clinical picture is characterized, in most cases, by progressive dyspnea and non-productive cough. In some cases, hemoptysis and chest pain are found. Onset can be acute, sub-acute, or chronic. Pulmonary involvement could be assessed by High Resolution Computed Tomography (HRCT), which may identify early manifestations of diseases. Moreover, Computed Tomography (CT) appearances can be highly variable depending on the positivity of myositis-specific autoantibodies. The most common pathological patterns include fibrotic and cellular nonspecific interstitial pneumonia or organizing pneumonia; major findings observed on HRCT images are represented by consolidations, ground-glass opacities, and reticulations. Other findings include honeycombing, subpleural bands, and traction bronchiectasis. In patients having Anti-ARS Abs, HRCT features may develop with consolidations, ground glass opacities (GGOs), and reticular opacities in the peripheral portions; nonspecific interstitial pneumonia or nonspecific interstitial pneumonia mixed with organizing pneumonia have been reported as the most frequently encountered patterns. In patients with anti-MDA5 Abs, mixed or unclassifiable patterns are frequently observed at imaging. HRCT is a sensitive method that allows one not only to identify disease, but also to monitor the effectiveness of treatment and detect disease progression and/or complications; however, radiological findings are not specific. Therefore, aim of this pictorial essay is to describe clinical and radiological features of interstitial lung diseases associated with polymyositis and dermatomyositis, emphasizing the concept that gold standard for diagnosis and classification-should be based on a multidisciplinary approach.

Clinical and radiological features of lung disorders related to connective-tissue diseases: a pictorial essay.

Connective tissue diseases (CTDs) include a spectrum of disorders that affect the connective tissue of the human body; they include autoimmune disorders characterized by immune-mediated chronic inflammation and the development of fibrosis. Lung involvement can be misdiagnosed, since pulmonary alterations preceded osteo-articular manifestations only in 20% of cases and they have no clear clinical findings in the early phases. All pulmonary structures may be interested: pulmonary interstitium, airways, pleura and respiratory muscles. Among these autoimmune disorders, rheumatoid arthritis (RA) is characterized by usual interstitial pneumonia (UIP), pulmonary nodules and airway disease with air-trapping, whereas non-specific interstitial pneumonia (NSIP), pulmonary hypertension and esophageal dilatation are frequently revealed in systemic sclerosis (SSc). NSIP and organizing pneumonia (OP) may be found in patients having polymyositis (PM) and dermatomyositis (DM); in some cases, perilobular consolidations and reverse halo-sign areas may be observed. Systemic lupus erythematosus (SLE) is characterized by serositis, acute lupus pneumonitis and alveolar hemorrhage. In the Sjögren syndrome (SS), the most frequent pattern encountered on HRCT images is represented by NSIP; UIP and lymphocytic interstitial pneumonia (LIP) are reported with a lower frequency. Finally, fibrotic NSIP may be the interstitial disease observed in patients having mixed connective tissue diseases (MCTD). This pictorial review therefore aims to provide clinical features and imaging findings associated with autoimmune CTDs, in order to help radiologists, pneumologists and rheumatologists in their diagnoses and management.

Automatic quantitative computed tomography measurement of longitudinal lung volume loss in interstitial lung diseases.

OBJECTIVES: To compare the lung CT volume (CTvol) and pulmonary function tests in an interstitial lung disease (ILD) population. Then to evaluate the CTvol loss between idiopathic pulmonary fibrosis (IPF) and non-IPF and explore a prognostic value of annual CTvol loss in IPF. METHODS: We conducted in an expert center a retrospective study between 2005 and 2018 on consecutive patients with ILD. CTvol was measured automatically using commercial software based on a deep learning algorithm. In the first group, Spearman correlation coefficients (r) between forced vital capacity (FVC), total lung capacity (TLC), and CTvol were calculated. In a second group, annual CTvol loss was calculated using linear regression analysis and compared with the Mann-Whitney test. In a last group of IPF patients, annual CTvol loss was calculated between baseline and 1-year CTs for investigating with the Youden index a prognostic value of major adverse event at 3 years. Univariate and log-rank tests were calculated. RESULTS: In total, 560 patients (4610 CTs) were analyzed. For 1171 CTs, CTvol was correlated with FVC (r: 0.86) and TLC (r: 0.84) (p < 0.0001). In 408 patients (3332 CT), median annual CTvol loss was 155.7 mL in IPF versus 50.7 mL in non-IPF (p < 0.0001) over 5.03 years. In 73 IPF patients, a relative annual CTvol loss of 7.9% was associated with major adverse events (log-rank, p < 0.0001) in univariate analysis (p < 0.001). CONCLUSIONS: Automated lung CT volume may be an alternative or a complementary biomarker to pulmonary function tests for the assessment of lung volume loss in ILD. KEY POINTS: • There is a good correlation between lung CT volume and forced vital capacity, as well as for with total lung capacity measurements (r of 0.86 and 0.84 respectively, p < 0.0001). • Median annual CT volume loss is significantly higher in patients with idiopathic pulmonary fibrosis than in patients with other fibrotic interstitial lung diseases (155.7 versus 50.7 mL, p < 0.0001). • In idiopathic pulmonary fibrosis, a relative annual CT volume loss higher than 9.4% is associated with a significantly reduced mean survival time at 2.0 years versus 2.8 years (log-rank, p < 0.0001).

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 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.

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.

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.

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.

[Clinical characteristics of patients with antisynthetase syndrome and interstitial pulmonary disease].

Objective: To provide reference for clinicians in diagnosis and treatment of antisynthetase syndrome with interstitial pulmonary disease (ASS-ILD) by analyzing the clinical features, imaging features and pulmonary function changes of ASS-ILD patients. Methods: A total of 92 patients with ASS-ILD diagnosed in the Respiratory Center of China-Japan Friendship Hospital from January 2015 to May 2018 were included, clinical manifestations, high-resolution computed tomography (HRCT), pulmonary function test, treatment and outcome were retrospectively analyzed. Results: The average age of the 92 patients was (58.6±12.2) years with a ratio of male to female 1∶1.79. The main types of anti-synthetase antibody were anti-Jo-1 antibody (37 cases, 40.2%) and anti EJ antibody (26 cases, 28.3%). The most common symptoms of ASS-ILD were cough (79 cases, 85.9%), shortness of breath (60 cases, 65.2%), expectoration (54 cases, 58.7%), fever (34 cases, 36.9%), and common signs were craftsman's hand (30 cases, 32.6%) and joint pain (23 cases, 25.0%). The most common imaging findings in HRCT were ground-glass opacities(68 cases, 73.9%), reticulations (45 cases, 48.9%), tractive bronchiectasis (40 cases, 43.5%) and consolidation (39 cases, 42.4%). The most common types of ILD were non-specific interstitial pneumonia (NSIP) (63 cases, 68.5%), followed by NSIP-organic pneumonia (OP) (12 cases, 13.0%). The main type of lung function impairment was mild restrictive ventilation dysfunction. There were no significant differences in clinical features, imaging findings and pulmonary function changes in different subtypes of ASS-ILD patients (all P>0.05). Corticosteroids was used in 78 (84.8%) of ASS-ILD patients, and 34 cases (37.0%) were given cyclophosphamide. A total of 91 patients (98.9%) were discharged with improvement and 1 anti-EJ positive patient died. Conclusions: ASS-ILD occurs frequently in middle-aged and old women. Respiratory symptoms, craftsman's hands and arthritis are the most common clinical manifestations. The most common imaging types of ILD are NSIP and NSIP-OP. Corticosteroids is commonly used for treatment.

[The clinical features and prognosis of interstitial lung disease patients with positive anti-neutrophil cytoplasmic antibody].

Objective: To investigate the clinical features and prognosis of interstitial lung disease patients with positive anti-neutrophil cytoplasmic antibody. Methods: The patients with interstitial lung disease who visited Peking Union Medical College Hospital from March 2006 to March 2016 were divided into three groups: interstitial lung disease with ANCA-positive(ANCA-ILD), connective tissue disease associated interstitial lung disease and interstitial pneumonia with autoimmune features (CTD-ILD/IPAF) and idiopathic interstitial pneumonia (IIP). The three groups were analyzed in terms of clinical manifestations, serology, lung function, imaging, survival and recurrence. Results: Two hundred and seventy four patients were enrolled and 38 (14%) were ANCA-positive of whom 16 were male and 22 were female. The age of 38 ANCA-positive patients was (59±10) years and the follow-up time was (52±31) months. Seven among the 38 ANCA-positive patients died and the death rate is 18.42%. The ANCA-positive patients with interstitial lung disease have higher onset age (ANCA-ILD:59±10,CTD-ILD/IPAF:52±10,IIP:53±11,H=19.29, P<0.001), lower hemoglobin (ANCA-ILD: 129±21, CTD-ILD/IPAF: 138±15, IIP: 140±19, H=8.17, P=0.017), higher erythrocyte sedimentation rate (ANCA-ILD:45±35, CTD-ILD/IPAF:26±24,IIP:19±22,H=19.73, P<0.001), lower lung function improvement rate after treatment (ANCA-ILD:31%,CTD-ILD/IPAF:59%,IIP: 39%,χ(2)=11.74,P=0.003), lower absorption rate of CT lesion (ANCA-ILD:61%,CTD-ILD/IPAF:82%,IIP:67%, χ(2)=9.23,P=0.010) and higher death rate(ANCA-ILD:18%,CTD-ILD/IPAF:6%,IIP:12%, χ(2)=7.16,P=0.028). Conclusions: There are significant differences in clinical characteristics between ANCA-positive patients and other types of pulmonary interstitial disease. And both the treatment effect and the prognosis is poor for the ANCA-positive patients.

[Characteristics and clinical significance of pulmonary function test and KL-6 in ASSD-ILD and IPF].

Objective: To study the characteristics and clinical significance of pulmonary function test and kerbs von den lungen 6 (KL-6) in anti-synthetase syndrome related interstitial lung disease (ASSD-ILD) and idiopathic pulmonary fibrosis (IPF). Methods: The clinical data of 43 patients with ASSD-ILD (ASSD-ILD group) from May 2015 to May 2017 were collected retrospectively, including 12 males and 31 females, and 34 patients with IPF (IPF group) treated in the First Affiliated Hospital of Zhengzhou University during the same period, including 28 males and 6 females, were also included. The basic information, and the value of pulmonary function test [pulmonary function parameters included the forced vital capacity expressed as percent predicted (FVC%pred), the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred), the ratio of FVC to FEV(1) (FVC/FEV(1)), the peak expiratory flow expressed as percent predicted (PEF%pred), the forced expiratory flow at 25%, 50%, 75% of FVC as percent predicted (FEF(25)%pred, FEF(50)%pred, and FEF(75)%pred), the maximum mid-expiratory flow as percent predicted (MMEF% pred), and the diffusing capacity for carbon monoxide as percent predicted (DLCO% pred)], and serum KL-6 level in ASSD-ILD and IPF were compared. Results: The FEV(1)%pred, FEF(50)%pred, FEF(75)%pred, and MMEF%pred values in ASSD-ILD group were significantly lower than those in IPF group (all P<0.05), while the FVC% pred, FVC/FEV(1), PEF% pred, FEF(25)%pred, and DLCO% pred values in ASSD-ILD group had no significant difference compared with IPF group (all P>0.05). There was no significant difference in serum KL-6 level between ASSD-ILD group and IPF group [(1 169±911) vs (1 210±908) U/ml, t=0.62, P=0.463]. Follow-up analysis showed that the serum KL-6 level of ASSD-ILD patients who died within two years was significantly higher than that of survivors [(2 060±1 168) vs (1 042±858) U/ml, t=2.93, P=0.041]. The serum KL-6 level of patients who died within two years of IPF patients was also significantly higher than that of patients who survived [(1 767±865) vs (1 089±894) U/ml, t=2.53, P=0.026]. The serum KL-6 level in ASSD-ILD group was negatively correlated with FVC%pred (r=-0.43, P=0.004), FEV(1)%pred (r=-0.39, P=0.010) and DLCO% pred (r=-0.41, P=0.006). There was no correlation between serum KL-6 level and pulmonary function test indexes in IPF group (all P>0.05). Conclusions: There is difference in pulmonary function test between ASSD-ILD patients and IPF patients. High serum KL-6 level will be predictive of poor prognosis.

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.

[The diagnostic value of serum KL-6 in connective tissue disease associated interstitial lung disease].

Objective: To evaluate the diagnostic value of the serum Krebs von den Lungen-6 (KL-6) for the interstitial lung disease associated with connective tissue diseases (CTD-ILD). Methods: 84 patients with CTD-ILD (CTD-ILD group) and 91 patients with connective tissue disease (CTD group) who visited the department of rheumatology and immunology of People's Hospital of Xinjiang Uygur Autonomous Region between January, 2016 and December, 2017 were included. Serum KL-6 levels were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits. Results: The significantly higher levels of KL-6 were determined in the CTD-ILD group than CTD group [1 239 (577, 2 094) vs 152 (89, 280) U/ml] (P<0.001). The optimal cutoff value of serum KL-6 for diagnosis of CTD-ILD was 402 U/ml, and the sensitivity and specificity were 82.1% and 86.8%, respectively. Area Under the Curve (AUC) was 0.905. Logistic regression analysis revealed that elevated KL-6 and decreased Carbon monoxide diffusion capacity were independently correlated with the occurrence of CTD-ILD, the decreased of DLcoSB% (OR=0.928, 95%CI: 0.891-0.968) and increase of KL-6 level (OR=1.005, 95%CI: 1.003-1.007) was the independent risk factor for the occurrence of ILD. Conclusion: The serum KL-6 is an important biomarker for the diagnosis of CTD-ILD and when the level of KL-6 is increased, the ILD should be alert.

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 value of myositis antibodies in patients with connective tissue disease-associated interstitial lung diseases].

Objective: To investigate the clinical significance of detection of myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) in patients with connective tissue disease-associated interstitial lung diseases (CTD-ILD). Methods: Serum samples of 120 patients with CTD-ILD admitted to the Department of Respiratory, Affiliated Drum Tower Hospital of Nanjing University Medical College from December 2016 to April 2018 were collected for analysis. The patients included 45 with polymyositis/dermatomyositis (PM/DM), 36 with Sjogren's syndrome (SS) and 39 with undifferentiated connective tissue disease (UCTD). There were 37 males and 83 females with an average age of (56±11) years. Thirty-two patients with non-CTD-ILD, 10 males and 22 females with an average age of (42±17) years, were enrolled as the control group. Euroline Autoimmune Inflammatory Myopathies 16 Ag kit was used for detecting MSAs and MAAs, and the positive rates of serum MSAs and MAAs were calculated. The antibody distribution and clinical characteristics of different groups were analyzed and compared. Results: Eighty-nine of the 120 patients with CTD-ILD were positive for MSA and/or MAA (74.2%), and the detection rates of MSAs and MAAs were 52.5% (63/120) and 61.7% (74/120) respectively. No myositis antibody was detected in the non-CTD-ILD group. The detection rates of MSAs in PM/DM-ILD group, SS-ILD group and UCTD-ILD group were 75.6% (34/45), 33.3%(12/36) and 43.6%(17/39) respectively. The total detection rate of MSAs in PM/DM group was significantly higher than that in SS group and UCTD group (χ(2)=14.53, 8.95, 0.01). The anti-ARS was the most frequent (50/120, 41.7%). The positive rates of MAAs in the three groups were 64.4%(29/45), 77.8%(28/36), 43.6%(17/39) respectively, and anti-Ro-52 accounted for 60%(72/120), and were highly correlated with MSAs such as anti-Jo-1 antibodies. Conclusion: Myositis antibody profiling should be performed in patients with ILD who were negative for conventional autoimmune antibody testing and had no CTD. In patients with SS-ILD and UCTD-ILD, the myositis antibody spectrum could detect the presence of myositis-specific antibodies and myositis-related antibodies in some patients, and its role in clinical diagnosis and treatment needed further observation.