Chinese Medical Sciences Journal ›› 2022, Vol. 37 ›› Issue (4): 293-302.doi: 10.24920/004067
收稿日期:
2022-01-22
接受日期:
2022-07-12
出版日期:
2022-12-31
发布日期:
2022-08-24
通讯作者:
施举红
E-mail:shijh@pumch.cn
Yu Gu,Ting Zhang,Min Peng,Juhong Shi*()
Received:
2022-01-22
Accepted:
2022-07-12
Published:
2022-12-31
Online:
2022-08-24
Contact:
Juhong Shi
E-mail:shijh@pumch.cn
摘要:
目的 评估继发于显微镜下多血管炎(microscopic polyangiitis,MPA)的弥漫性肺泡出血和/或肺间质病患者的临床特征以及预后相关因素。
方法 回顾性分析2002年至2012年于北京协和医院内科住院的MPA患者,根据肺受累类型不同分为单纯肺间质病组、单纯弥漫性肺泡出血组、弥漫肺泡出血合并肺间质病组和无肺受累组。比较各组患者人口学资料、全身症状、脏器受累情况、实验室检查、治疗与预后。采用Logistic回归和Cox分析患者早期与晚期死亡的危险因素。
结果 共181例MPA患者纳入研究,其中单纯肺间质病组96例、单纯弥漫性肺泡出血组19例、弥漫肺泡出血合并肺间质病组18例、无肺受累组48例。随访时间的中位数为67个月(范围:1~199个月)。单纯弥漫性肺泡出血组肾脏受累最严重(血肌酐中位值:449 μmol/L,显著高于单纯肺间质病组(123 μmol/L,Nemenyi = -35.215,P = 0.045)和弥漫肺泡出血合并肺间质病组(359 μmol/L,Nemenyi = -43.609,P = 0.007)。单纯肺间质病组患者年龄大于单纯弥漫性肺泡出血组(中位年龄:69比57岁;Nemenyi = 43.853,P = 0.005)。弥漫肺泡出血合并肺间质病组患者融合了两种单纯亚型患者的临床特点,并且死亡率最高(死亡率72.2%)。MPA患者总的5年生存率为51.9%。外周血白细胞升高(1月内死亡风险评估:OR = 1.103,95%CI:1.008-1.207,P = 0.032;1年内死亡风险评估:OR = 1.103,95%CI:1.026-1.186,P = 0.008)是MPA患者早期死亡的高危因素。高龄(HR = 1.044,95%CI:1.023-1.066,P < 0.001)、肾功能严重受损(HR = 1.001,95%CI:1.000-1.002,P = 0.032)及心血管受累(HR = 2.093,95%CI:1.195-3.665,P = 0.010)是MPA患者晚期死亡的高危因素。在诊断后1年内共有49例患者发生过肺部感染。肺部感染是MPA患者最主要的死亡原因(38/54),以肺间质病患者尤为明显。
结论 不同肺受累模式的MPA患者具有完全不同的临床特征,提示不同肺受累模式的MPA可能存在不同的发病机制。因此,对继发于MPA的弥漫性肺泡出血和肺间质病应按照不同的临床亚型分别研究。
Yu Gu, Ting Zhang, Min Peng, Juhong Shi. Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease[J].Chinese Medical Sciences Journal, 2022, 37(4): 293-302.
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Variable | DAH | DAH+ILD | ILD | NPI | Statistic | P value |
---|---|---|---|---|---|---|
No. of patients [n (%)] | 19 (10.5) | 18 (9.9) | 96 (53.0) | 48 (26.5) | ||
Age at diagnosis [yrs, median (range)] | 57 (47-65)a | 64 (59-75) | 69 (60-74)a | 65 (53-74) | H = 12.13 | 0.007 |
Male [n (%)] | 7 (36.8) | 8 (44.4) | 50 (52.1) | 20 (41.7) | χ2 = 2.378 | 0.498 |
Follow-up time [months, median (range)] | 54 (5-105) | 31 (3-78) | 50 (15-100) | 78 (57-112) | H = 2.545 | 0.058 |
BVAS [score, median (range)] | 22 (18-28) | 21 (12-25) | 21 (15-27) | 21 (15-29) | H = 1.955 | 0.582 |
FFS2009 [score, mean±SD] | 2.01±0.97 | 2.22±0.81 | 1.88±0.77 | 1.81±0.76 | H = 3.356 | 0.340 |
Fever [n (%)] | 4 (21.1) | 6 (33.3) | 25 (26.0) | 14 (29.2) | Fisher’s exact χ2=0.927 | 0.831 |
Weight loss [n (%)] | 6 (31.6) | 9 (50.0) | 48 (50.0) | 26 (54.2) | χ2 = 2.863 | 0.413 |
Organ involvement [n (%)] | ||||||
Renal | 18 (94.7) | 18 (100) | 83 (86.5) | 43 (89.6) | Fisher’s exact χ2=2.951 | 0.398 |
Nervous system | 5 (26.3) | 3 (16.7) | 40 (41.7) | 21 (48.3) | χ2 = 5.791 | 0.122 |
ENT | 2 (10.5) | 1 (5.6) | 14 (14.6) | 12 (25.0) | Fisher’s exact χ2=4.263 | 0.235 |
Skin | 4 (21.1) | 3 (16.7) | 10 (10.4) | 8 (16.7) | Fisher’s exact χ2=2.702 | 0.433 |
Cardiovascular system | 4 (21.1) | 3 (16.7) | 8 (8.3) | 3 (6.3) | Fisher’s exact χ2=4.589 | 0.171 |
Eyes | 1 (5.3) | 0 | 5 (5.2) | 5 (10.4) | Fisher’s exact χ?=2.294 | 0.467 |
Abdomen | 3 (15.8) | 1 (5.6) | 2 (2.1) | 3 (6.3) | Fisher’s exact χ2=6.237 | 0.064 |
Laboratory findings | ||||||
WBC [×??9/L, median (range)] | 10.1 (8.1-18.0) | 9.4 (7.9-13.7) | 10.0 (7.4-13.7) | 9.6 (6.8-12.8) | H = 2.510 | 0.473 |
HGB (g/L, mean±SD)* | 88±30b | 92±22 | 107±22b,c | 96±19c | F = 5.952 | 0.001 |
PLT (×109/L, median (range)) | 291 (209-429) | 228 (132-308) | 278 (194-363) | 260 (230-405) | H = 5.387 | 0.146 |
ESR (mm/h, mean±SD)* | 78 ± 40 | 73 ± 42 | 75±31 | 77±31 | F = 0.144 | 0.933 |
CRP (mg/L, median (range)) | 39 (18-70) | 21 (13-73) | 45 (10-91) | 58 (14-127) | H = 0.902 | 0.825 |
Creatinine [μmol/L, median (range)] | 449 (126-523)d,e | 357 (156-640)e | 123 (81-230)d | 170 (104-385) | H = 16.572 | 0.001 |
ANA [n (%)] | 28 (29.2) | 7 (38.9) | 7 (36.8) | 16 (33.3) | χ2 = 0.990 | 0.825 |
ANCA [n (%)] | Fisher’s exact χ2=10.309 | 0.185 | ||||
PR3/c-ANCA | 5 (5.3) | 0 | 2 (2.1) | 2 (4.2) | >0.05 | |
MPO/p-ANCA | 17 (89.5) | 16 (88.9) | 92 (95.8) | 44 (91.7) | >0.05 | |
MPO/p-ANCA+PR3/c-ANCA positive | 0 | 2 (11.1) | 1 (1.0) | 2 (4.2) | >0.05 | |
MPO/p-ANCA+PR3/c-ANCA negative | 1 (5.3) | 0 | 1 (1.0) | 0 | >0.05 | |
Treatments | ||||||
p-GC/h-GC/n-GC (n) | 8/11/0 | 8/10/0 | 20/73/3 | 17/31/0 | Fisher’s exact χ2=8.867 | 0.129 |
iv-CTX/po-CTX/n-CTX (n) | 11/4/4 | 11/4/3 | 53/33/10 | 25/15/8 | Fisher’s exact χ2=3.848 | 0.704 |
IVIG [n (%)] | 2 (10.5) | 5 (27.8)g | 3 (3.1)g | 3 (6.3) | Fisher’s exact χ2=11.062 | 0.005 |
PE [n (%)] | 3 (15.8) | 5 (27.8)h | 1 (1.0)h,i | 1 (2.1)i | Fisher’s exact χ2 =18.792 | <0.001 |
Prognosis [n (%)] | ||||||
Pulmonary infections in one year | 4 (8.2) | 4 (8.2) | 34 (69.4) | 7 (14.3) | Fisher’s exact χ2=7.590 | 0.051 |
Deaths in one year | 8 (42.1) | 7 (38.9) | 22 (22.9) | 9 (18.8) | Fisher’s exact χ2=5.870 | 0.115 |
Deaths overall | 11 (57.9) | 13 (72.2) | 58 (60.4) | 20 (41.7) | χ2 = 6.715 | 0.082 |
"
Variables | Death in one year | Death in one month | |||||
---|---|---|---|---|---|---|---|
OR | 95%CI | P value | OR | 95%CI | P value | ||
Age | 1.047 | 1.009, 1.086 | 0.016 | 1.066 | 0.995, 1.142 | 0.080 | |
Male | 0.993 | 0.465, 2.121 | 0.905 | 0.537 | 0.113, 2.333 | 0.866 | |
Fever | 1.775 | 0.690, 4.566 | 0.302 | ||||
DAH | 2.164 | 0.864, 5.418 | 0.078 | 4.358 | 1.277, 14.877 | 0.019 | |
Cardiovascular system | 2.013 | 0.661, 6.129 | 0.145 | ||||
Skin/mucosa | 5.110 | 1.392, 18.758 | 0.014 | ||||
Abdomen | 3.744 | 0.419, 33.492 | 0.272 | ||||
WBC | 1.103 | 1.026, 1.186 | 0.008 | 1.103 | 1.008, 1.207 | 0.032 | |
HGB | 0.978 | 0.944, 1.014 | 0.240 | ||||
Creatinine | 1.002 | 1.000, 1.003 | 0.011 | 1.001 | 0.998, 1.004 | 0.430 |
"
Variables | Cox regression | Logistic regression | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | OR | 95%CI | P value | ||
Age | 1.044 | 1.023, 1.066 | <0.001 | 1.061 | 1.030, 1.094 | < 0.001 | |
Male | 0.803 | 0.539, 1.196 | 0.314 | 0.761 | 0.387, 1.497 | 0.366 | |
ILD | 1.389 | 0.904, 2.134 | 0.145 | 1.623 | 0.792, 3.324 | 0.185 | |
Cardiovascular system | 2.093 | 1.195, 3.665 | 0.010 | 6.216 | 1.260, 30.664 | 0.025 | |
WBC | 1.040 | 1.002, 1.079 | 0.039 | 1.024 | 0.955, 1.098 | 0.503 | |
HGB | 1.021 | 1.004, 1.038 | 0.016 | ||||
Creatinine | 1.001 | 1.000, 1.002 | 0.032 | 1.003 | 1.001, 1.005 | 0.003 |
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