Clinical Analysis Of Ancaassociated Vasculitis Patients With Interstitial Lung Disease

Objective: To investigate the clinical characteristics and related risk factors of patients with antineutrophil cytoplasmic antibody(ANCA)associated vasculitis(AAV)complicated with interstitial lung disease.the clinical features and chest high resolution computed tomography(HRCT)features of AAV patients with interstitial lung disease(AAV-ILD)with different ANCA serotypes were compared.To study the prognostic risk factors of early death in patients with AAV-ILD,to further guide the clinical diagnosis and treatment,and to improve the prognosis of the patients.Methods:The clinical data of 152 patients with AAV in Tianjin Medical University General Hospital from January 1,2010 to October 31,2018 were analyzed retrospectively and followed up.According to the presence or absence of ILD,the clinical characteristics and survival differences of the two groups were compared,and111 patients in AAV-ILD group were divided into two groups according to ANCA serotype,and the clinical features and chest HRCT,features of the two groups were compared.Logistic regression model was used to analyze the risk factors of AAV complicated with ILD,and Cox regression model was used to analyze the risk factors of early death in AAV-ILD group.Results:There were 152 patients with AAV,including 69 males(45.4%)and 83females(54.6%),the average age of onset was 63.74 ±12.25 years old,and the median course of disease was 2.9 months(quartile interval [IQR] 1.63,9.30).MPA was diagnosed in 108 cases(71.1%),GPA in 37 cases(24.3%),EGPA in 7 cases(4.6%).At the end of follow-up,125 patients with known follow-up period of 0.1 ~94.8 months,and the median follow-up time was 23.1 months(IQR: 5.2,55.4).Firstly,the clinical characteristics of patients in AAV-ILD group(n=115,75.7%)were compared with AAV-NILD group(n=37,24.3%): the onset age was higher(65.94±10.20 years old,vs 56.89 ±15.38 years old,P =0.002),BVAS ≥ 15 points(65.2% vs43.2%,P =0.018)and cough and expectoration symptoms(64.3% vs 37.8%,P=0.007)were more common,the level of serum RF was higher(27.20 ±114.00 vs 20.00±6.50,P=0.007),and more MPO-ANCA positive(82.6% vs 62.2%,P = 0.009)in AAV-ILD group,while PR3-ANCA was rare(14.8% vs 35.1%,P = 0.007),and differences were statistically significant.The levels of serum CA199(11.61±27.58 vs 6.56±11.04,P=0.032),CA242(4.90±9.90 vs 3.25± 4.51,P= 0.041),CA153(13.60±21.50 vs10.55±6.85,P=0.040),and CEA(2.23±2.31 vs 1.73 ±1.16,P=0.003)in patients with pulmonary fibrosis were higher than that without pulmonary fibrosis.Of the 125 patients with known follow-up period,98 patients with ILD,41 patients died(41.8%,41 /98),27 patients without ILD and 7 patients died(25.9%,7 / 27).There was no significant difference in mortality between the two groups(P = 0.071).Secondly,the clinical manifestations and chest HRCT characteristics of MPO-ANCA positive patients(n = 94,81.7%)and PR3-ANCA positive patients(n = 17,14.8%)in AAV-ILD group were compared: the onset age of MPO-ANCA positive patients was higher(67.49 ±8.92 years old vs 59.76 ±13.26 years old,P =0.003),ear,nose and throat(ENT)involvement was rare(35.1% vs 64.7%,0.022),serum CA199 level increased(z=-2.668,P=0.008),diffuse reticular shadow(54.3% vs 11.8%,P = 0.001)and honeycomb shadow(31.9% vs 0%,P =0.015)were more common in MPOANCA positive patients in Chest HRCT,and directly indicated pulmonary fibrosis(50.5% vs 17.6%,P =0.003)in Chest HRCT were more likely to occur,the difference was statistically significant.Thirdly,MPO-ANCA positive and PR3-ANCA positive were included in Logistic multivariate analysis with sex(male),age > 65 years,course of disease > 6 months,smoking history and BVAS score≥ 15 points,respectively.The results showed that MPO-ANCA was positive(OR:2.855,95%CI:1.152~7.077,P = 0.024)and BVAS score≥ 15 points(OR:2.669,95%CI:1.169~6.090,P=0.020 or OR:3.063,95%CI:1.311~7.154,P=0.010)were the risk factors of AAV complicated with ILD,while PR3-ANCA positive(OR:0.258,95%CI:0.099~0.670,P=0.005)was the protective factor of AAV complicated with ILD.Finally,in the died 41 AAV-ILD patients,29 cases died within 1 year(70.7%,29/41).Multivariate analysis of Cox regression model showed that age of diagnosis(OR:1.078,1.027 ~1.131,P < 0 01)and Cr level(OR:1.004,1.002 ~1.005,P < 0 01)were independent risk factors for early death of AAV patients with ILD.Conclusion: 1.The onset age of AAV patients with ILD was older,and most of them showed disease activity.2.Patients with positive MPO-ANCA were more likely to develop pulmonary interstitial lesions,thoracic HRCT were more likely to develop honeycomb shadow and reticular shadow,and directly suggest pulmonary fibrosis was more common,which affected the prognosis of patients.Attention should be paid to the screening of ANCA antibody and pulmonary HRCT monitoring in order to diagnose and intervene in time and improve the prognosis.3.Serum CA199,CA242,CA153 and CEA may be involved in the pathogenesis of AAV-ILD,and may be used as indicators to evaluate the severity of pulmonary fibrosis in the future.4.The early mortality rate of patients with AAV complicated with ILD is extremely high,and the level of creatinine at the time of diagnosis and elderly patients is independent risk factors for early death in patients with ILD.