具有自身免疫特征的间质性肺炎的临床特点及支气管肺泡灌洗液细胞分类的应用

Clinical characteristics of interstitial pneumonia with autoimmune features and application of bronchoalveolar lavage fluid

目的探讨具有自身免疫特征的间质性肺炎(IPAF)的临床特点及其支气管肺泡灌洗液(BALF)细胞分类特征与应用。方法本研究为病例对照研究。采用目的抽样法选取2021年3月至2023年9月于首都医科大学附属北京安贞医院诊治的行支气管肺泡灌洗的IPAF患者56例,根据使用糖皮质激素前后的临床症状和胸部高分辨CT情况分为有效组(39例)和无效组(17例)。收集所有患者的一般情况(性别、年龄、吸烟、合并症),临床表现,辅助检查(血清学、影像特征、BALF分类、肺功能),以及糖皮质激素治疗反应情况,分析疾病临床特点。比较2组患者BALF分类淋巴细胞百分比,以及治疗前后用力肺活量占预计值百分比(FVC%pred)、肺总量占预计值百分比(TLC%pred)和肺一氧化碳弥散量占预计值百分比(DLCO%pred)水平。采用logistic回归分析影响IPAF患者糖皮质激素疗效的因素。结果共纳入IPAF患者56例,其中男22例,女34例;年龄(62.8±8.5)岁,年龄范围为43~78岁。所有患者均存在咳嗽,其中伴气短者51例(91.1%);咳痰35例(62.5%);技工手(即远端手指皮肤裂纹)8例(14.3%);手掌或指腹毛细血管扩张7例(12.5%);炎性关节炎或多关节晨僵>60 min 14例(25.0%);不明原因手指肿胀11例(19.6%);雷诺现象3例(5.4%)。所有IPAF患者血清学指标均为阳性,常见的血清学表现包括:抗核抗体阳性29例(51.8%),类风湿因子≥2倍正常上限3例(5.4%),抗环瓜氨酸肽抗体阳性1例(1.8%),抗SSA抗体阳性6例(10.7%)。IPAF患者胸部高分辨率CT主要表现为磨玻璃影(52/56,92.8%)、网格影(27/56,48.2%)、条索影(15/56,26.8%);影像分型最常见为非特异性间质性肺炎型(37/56,66.1%),其次为机化性肺炎型(9/56,16.1%)。BALF细胞分类以中性粒细胞和淋巴细胞混合升高为主(57.1%)。93.3%(14/15)技工手、手掌和指腹毛细血管扩张患者BALF淋巴细胞比例升高。磨玻璃影患者中86.5%(45/52)BALF淋巴细胞比例升高,94.2%(49/52)BALF中性粒细胞升高。有效组和无效组BALF分类淋巴细胞百分比分别为(26.4±13.8)%和(13.2±4.6)%,差异有统计学意义(t=3.84,P=0.009)。2组患者治疗前FVC%pred、TLC%pred和DLCO%pred比较差异均无统计学意义(均P>0.05);治疗后有效组以上各指标均高于无效组[(71.9±6.2)%比(65.4±6.2)%、(70.5±6.0)%比(64.0±6.1)%、(69.9±6.8)%比(65.1±8.4)%],差异均有统计学意义(均P<0.05)。较高的淋巴细胞比例会得到较好的糖皮质激素疗效(OR=0.407,95%CI:0.203~0.816,P=0.011)。结论IPAF以技工手、手掌或指腹毛细血管扩张较为常见,手部皮肤异常患者的BALF淋巴细胞比例较高;BALF细胞分类以淋巴细胞和中性粒细胞混合升高为主,较高的淋巴细胞比例会得到较好的糖皮质激素疗效。

Objective To explore the clinical chacracteristics of interstitial pneumonia with autoimmune features(IPAF),and characteristics and application of bronchoalveolar lavage fluid(BALF)cytology.Methods This was a case-control study.Totally 56 IPAF patients who underwent bronchoalveolar lavage in Beijing Anzhen Hospital,Capital Medical University from March 2021 to September 2023 were selected by purposive sampling method.They were assigned into effective group(n=39)and ineffective group(n=17)based on the clinical symptoms and high-resolution computed tomography(HRCT)before and after glucocorticoid.The general information(gender,age,smoking,comorbidities),clinical manifestations,auxiliary examinations(serological testing,imaging features,BALF cytology,lung function),and glucocorticoid response were collected to analyze the clinical characteristics of IPAF.BALF cytology,lymphocytes percentage,predicted forced vital capacity(FVC%pred),predicted total lung capacity(TLC%pred),predicted diffusing capacity of the lung for carbon monoxide(DLCO%pred)before and after treatment were compared between two groups.Logistic regression analysis was performed to identify the influencing factors for glucocorticoid efficacy in IPAF patients.Results A total of 56 IPAF patients representing 22 males and 34 females with the average age of 62.8±8.5(43-78)years were included.All patients had cough,and 51(91.1%)with dyspnea,35(62.5%)with expectoration.The common clinical manifestations of IPAF included mechanician hands(skin cracks on distal fingers)in 8(14.3%)cases,palm or fingertip telangiectasia in 7(12.5%)cases,inflammatory arthritis and multi-joint morning stiffness>60 min in 14(25.0%)cases,finger swollen in 11(19.6%)cases and Raynaud′s phenomenon in 3(5.4%)cases.All IPAF patients had positive serologic indicators.The common serologic manifestations included antinuclear antinbody positive in 29(51.8%)cases,rheumatoid factor≥2 times the upper normal limit in 3(5.4%)cases,positive anti-cyclic citrullinated peptide antibody in 1/(1.8%)case and positive anti-SSA antibody in 6(10.7%)cases.The most common manifestation visualizing on the chest high-resolution CT scan in IPAF patients was ground glass opacities(52/56,92.8%),followed by grid opacities(27/56,48.2%)and stripe opacities(15/56,26.8%).The most common imaging subtype was non-specific interstitial pneumonia(37/56,66.1%),followed by organized pneumonia(9/56,16.1%).The BALF cytology was mainly characterized by mixed elevation of neutrophils and lymphocytes(57.1%).93.3%(14/15)of patients with mechanician hands or telangiectasia in the palms/fingertips showed an increase in the proportion of BALF lymphocytes.86.5%(45/52)of patients with ground glass opacity in HRCT had increased proportion of lymphocytes in BALF.94.2%(49/52)BALF neutrophils increased.There was a significant difference in the proportion of lymphocytes in BALF between effective group and ineffective group([26.4±13.8]%vs[13.2±4.6]%,t=3.84,P=0.009).There were no significant differences in FVC%pred,TLC%pred,and DLCO%pred before treatment between the two groups(P>0.05).After treatment,the FVC%pred([71.9±6.2]%vs[65.4±6.2]%),TLC%pred([70.5±6.0]%vs[64.0±6.1]%)and DLCO%pred([69.9±6.8]%vs[65.1±8.4]%)in the effective group were significantly higher than those of the ineffective group(all P<0.05).The higher proportion of lymphocytes in BALF cytology was significantly correlated with a better glucocorticoid efficacy(OR=0.407,95%CI:0.203-0.816,P=0.011).Conclusions Mechanician hands and telangiectasia in the palms or fingertips are common clinical manifestations of IPAF.Patients with abnormal hand skin have a higher proportion of lymphocytes.BALF cytology is mainly characterized by a mixed increase in lymphocytes and neutrophils,and a higher proportion of lymphocytes might be associated with a better effect of glucocorticoids.