Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease

Yu Gu; Ting Zhang; Min Peng; Juhong Shi

doi:10.24920/004067

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Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease

Chinese Medical Sciences Journal Vol. 37, Issue 4, Pages: 293-302(2022)

Original article | Updated：2024-04-10

- Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease
- Affiliations：
  
  Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
- Author bio：
  
  * shijh@pumch.cn, Tel: 86-13701178492
- Funds：
- DOI：10.24920/004067
  CLC：
- Received：22 January 2022，
  
  Accepted：2022-7-12，
  
  Published Online：24 August 2022，
  
  Published：31 December 2022
- Accepted：
Scan QR Code
Yu Gu, Ting Zhang, Min Peng, et al. 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.
DOI：

Yu Gu, Ting Zhang, Min Peng, et al. 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. DOI： 10.24920/004067.

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，

= 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，

= 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：

= 1.103，95%

：1.008-1.207，

= 0.032；1年内死亡风险评估：

= 1.103，95%

：1.026-1.186，

= 0.008）是MPA患者早期死亡的高危因素。高龄（

= 1.044，95%

：1.023-1.066，

0.001）、肾功能严重受损（

= 1.001，95%

：1.000-1.002，

= 0.032）及心血管受累（

= 2.093，95%

：1.195-3.665，

= 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。

Abstract

Objective

To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage (DAH) and/or interstitial lung disease (ILD) secondary to microscopic polyangiitis (MPA) in a Chinese general hospital.

Methods

We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and 2012. The patients were divided into the ILD

DAH

DAH combined with ILD (DAHILD)

and no pulmonary involvement (NPI) groups according to pulmonary involvement patterns. The clinical characteristics at diagnosis were analyzed. The risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox analysis.

Results

Of 193 newly diagnosed MPA patients

181 patients were enrolled in the research

of which 19 had DAH alone

96 had ILD alone

18 had DAH and DAH concurrently

and 48 had NPI. The median of serum creatine level in the DAH group was 449 μmol/L

significantly higher than that in the ILD group (123 μmol/L

Nemenyi

= -35.215

= 0.045) and DAHILD group (359 μmol/L

Nemenyi

= -43.609

P =

0.007). The median follow-up time was 67 (range: 1-199) months. Patients in the ILD group were older than those in the DAH group (median: 69 years

. 57 years

Nemenyi

= 43.853

= 0.005). The patients with both DAH and ILD had combined features of the two subtypes

and the highest mortality (72.2% at the end of follow-up). The elevated white blood cell count was a risk factor for short-term death (

= 1.103

95%

: 1.008-1.207

= 0.032 for one month;

= 1.103

95%

: 1.026-1.186

= 0.008 for one year). Old age (

= 1.044

95%

: 1.023-1.066

0.001)

cardiovascular system involvement (

= 2.093

95%

: 1.195-3.665

= 0.010)

poor renal function (

= 1.001

95%

: 1.000-1.002

= 0.032) were risk factors for long-term death. Pulmonary infections (38/54) were the leading causes of death

especially for the patients with ILD. Besides

49 patients suffered from pulmonary infections in the first year after diagnosis.

Conclusions

MPA patients who presented with different pulmonary involvement patterns have completely different clinical features. These subtypes probably have different pathogenesis and should be studied separately.

关键词

Keywords

references

Lai QY , Ma TT , Li ZY , et al . Predictors for mortality in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: a study of 398 Chinese patients . J Rheumatol 2014 ; 41 ( 9 ): 1849 - 55 . doi: 10.3899/jrheum.131426 https://dx.doi.org/10.3899/jrheum.131426 . DOI: 10.3899/jrheum.131426 http://doi.org/10.3899/jrheum.131426 http://www.jrheum.org/lookup/doi/10.3899/jrheum.131426 http://www.jrheum.org/lookup/doi/10.3899/jrheum.131426

Yamagata M , Ikeda K , Tsushima K , et al . Prevalence and responsiveness to treatment of lung abnormalities on chest computed tomography in patients with microscopic polyangiitis: a multicenter, longitudinal, retrospective study of one hundred fifty consecutive hospital-based Japanese patients . Arthritis Rheumatol 2016 ; 68 ( 3 ): 713 - 23 . doi: 10.1002/art.39475 https://dx.doi.org/10.1002/art.39475 . DOI: 10.1002/art.39475 http://doi.org/10.1002/art.39475 https://onlinelibrary.wiley.com/doi/10.1002/art.39475 https://onlinelibrary.wiley.com/doi/10.1002/art.39475

Kim MJ , Shin K . Interstitial lung disease and diffuse alveolar hemorrhage, the two key pulmonary manifestations in microscopic polyangiitis . Tuberc Respir Dis (Seoul) 2021 ; 84 ( 4 ): 255 - 62 . doi: 10.4046/trd.2021.0065 https://dx.doi.org/10.4046/trd.2021.0065 . DOI: 10.4046/trd.2021.0065 http://doi.org/10.4046/trd.2021.0065 http://e-trd.org/journal/view.php?doi=10.4046/trd.2021.0065 http://e-trd.org/journal/view.php?doi=10.4046/trd.2021.0065

Katsumata Y , Kawaguchi Y , Yamanaka H . Interstitial lung disease with ANCA-associated vasculitis . Clin Med Insights Circ Respir Pulm Med 2015 ; 9 ( Suppl 1 ): 51 - 6 . doi: 10.4137/CCRPM.S23314 https://dx.doi.org/10.4137/CCRPM.S23314 . DOI: 10.4137/CCRPM.S23314 http://doi.org/10.4137/CCRPM.S23314

Jennette JC , Falk RJ , Andrassy K , et al . Nomenclature of systemic vasculitides. Proposal of an international consensus conference . Arthritis Rheum 1994 ; 37 ( 2 ): 187 - 92 . doi: 10.1002/art.1780370206 https://dx.doi.org/10.1002/art.1780370206 . DOI: 10.1002/art.1780370206 http://doi.org/10.1002/art.1780370206 http://doi.wiley.com/10.1002/%28ISSN%291529-0131 http://doi.wiley.com/10.1002/%28ISSN%291529-0131

Suppiah R , Robson JC , Grayson PC , et al . 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis . Ann Rheum Dis 2022 ; 81 ( 3 ): 321 - 6 . doi: 10.1136/annrheumdis-2021-221796 https://dx.doi.org/10.1136/annrheumdis-2021-221796 . DOI: 10.1136/annrheumdis-2021-221796 http://doi.org/10.1136/annrheumdis-2021-221796

Mukhtyar C , Lee R , Brown D , et al . Modification and validation of the Birmingham Vasculitis Activity Score (version 3) . Ann Rheum Dis 2009 ; 68 ( 12 ): 1827 - 32 . doi: 10.1136/ard.2008.101279 https://dx.doi.org/10.1136/ard.2008.101279 DOI: 10.1136/ard.2008.101279 http://doi.org/10.1136/ard.2008.101279

West S , Arulkumaran N , Ind PW , et al . Diffuse alveolar haemorrhage in ANCA-associated vasculitis . Intern Med 2013 ; 52 ( 1 ): 5 - 13 . doi: 10.2169/internalmedicine.52.8863 https://dx.doi.org/10.2169/internalmedicine.52.8863 . DOI: 10.2169/internalmedicine.52.8863 http://doi.org/10.2169/internalmedicine.52.8863 https://www.jstage.jst.go.jp/article/internalmedicine/52/1/52_52.8863/_article https://www.jstage.jst.go.jp/article/internalmedicine/52/1/52_52.8863/_article

Ahn JK , Hwang JW , Lee J , et al . Clinical features and outcome of microscopic polyangiitis under a new consensus algorithm of ANCA-associated vasculitides in Korea . Rheumatol Int 2012 ; 32 ( 10 ): 2979 - 86 . doi: 10.1007/s00296-011-2079-4 https://dx.doi.org/10.1007/s00296-011-2079-4 . DOI: 10.1007/s00296-011-2079-4 http://doi.org/10.1007/s00296-011-2079-4

Furuta S , Chaudhry AN , Hamano Y , et al . Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan . J Rheumatol 2014 ; 41 ( 2 ): 325 - 33 . doi: 10.3899/jrheum.130602 https://dx.doi.org/10.3899/jrheum.130602 . DOI: 10.3899/jrheum.130602 http://doi.org/10.3899/jrheum.130602

Kawai H , Banno S , Kikuchi S , et al . Retrospective analysis of factors predicting end-stage renal failure or death in patients with microscopic polyangiitis with mainly renal involvement . Clin Exp Nephrol 2014 ; 18 ( 5 ): 795 - 802 . doi: 10.1007/s10157-013-0926-1 https://dx.doi.org/10.1007/s10157-013-0926-1 . DOI: 10.1007/s10157-013-0926-1 http://doi.org/10.1007/s10157-013-0926-1

Homma S , Suzuki A , Sato K . Pulmonary involvement in ANCA-associated vasculitis from the view of the pulmonologist . Clin Exp Nephrol 2013 ; 17 ( 5 ): 667 - 71 . doi: 10.1007/s10157-012-0710-7 https://dx.doi.org/10.1007/s10157-012-0710-7 . DOI: 10.1007/s10157-012-0710-7 http://doi.org/10.1007/s10157-012-0710-7

Chen Y , Gao E , Yang L , et al . Long-term outcome of mycophenolate mofetil treatment for patients with microscopic polyangiitis: an observational study in Chinese patients . Rheumatol Int 2016 ; 36 ( 7 ): 967 - 74 . doi: 10.1007/s00296-016-3492-5 https://dx.doi.org/10.1007/s00296-016-3492-5 . DOI: 10.1007/s00296-016-3492-5 http://doi.org/10.1007/s00296-016-3492-5

Abe Y , Tamura N , Yang KS , et al . Predictive factors for mortality in elderly Japanese patients with severe microscopic polyangiitis: a retrospective single-center study . Mod Rheumatol 2017 ; 27 ( 2 ): 315 - 9 . doi: 10.1080/14397595.2016.1205778 https://dx.doi.org/10.1080/14397595.2016.1205778 . DOI: 10.1080/14397595.2016.1205778 http://doi.org/10.1080/14397595.2016.1205778

Lin Y , Zheng W , Tian X , et al . Antineutrophil cytoplasmic antibody-associated vasculitis complicated with diffuse alveolar hemorrhage: a study of 12 cases . J Clin Rheumatol 2009 ; 15 ( 7 ): 341 - 4 . doi: 10.1097/RHU.0b013e3181b59581 https://dx.doi.org/10.1097/RHU.0b013e3181b59581 . DOI: 10.1097/RHU.0b013e3181b59581 http://doi.org/10.1097/RHU.0b013e3181b59581

Hirayama K , Kobayashi M , Usui J , et al . Pulmonary involvements of anti-neutrophil cytoplasmic autoantibody-associated renal vasculitis in Japan . Nephrol Dial Transplant 2015 ; 30 (Suppl 1 ): i83 - 93 . doi: 10.1093/ndt/gfu385 https://dx.doi.org/10.1093/ndt/gfu385 . DOI: 10.1093/ndt/gfu385 http://doi.org/10.1093/ndt/gfu385 https://academic.oup.com/ndt/article/30/suppl_1/i83/2324812 https://academic.oup.com/ndt/article/30/suppl_1/i83/2324812

Hogan SL , Nachman PH , Wilkman AS , et al . Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis . J Am Soc Nephrol 1996 ; 7 ( 1 ): 23 - 32 . doi: 10.1681/ASN.V7123 https://dx.doi.org/10.1681/ASN.V7123 . DOI: 10.1681/ASN.V7123 http://doi.org/10.1681/ASN.V7123

Kostianovsky A , Hauser T , Pagnoux C , et al . Alveolar haemorrhage in ANCA-associated vasculitides: 80 patients’ features and prognostic factors . Clin Exp Rheumatol 2012 ; 30 (1 Suppl 70 ): S77 - 82 .

Nada AK , Torres VE , Ryu JH , et al . Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients . Mayo Clin Proc 1990 ; 65 ( 6 ): 847 - 56 . doi: 10.1016/s0025-6196(12)62575-0 https://dx.doi.org/10.1016/s0025-6196(12)62575-0 . DOI: 10.1016/s0025-6196(12)62575-0 http://doi.org/10.1016/s0025-6196(12)62575-0

Schirmer JH , Wright MN , Vonthein R , et al . Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort . Rheumatology (Oxford) 2016 ; 55 ( 1 ): 71 - 9 . doi: 10.1093/rheumatology/kev286 https://dx.doi.org/10.1093/rheumatology/kev286 . DOI: 10.1093/rheumatology/kev286 http://doi.org/10.1093/rheumatology/kev286

Arulkumaran N , Periselneris N , Gaskin G , et al . Interstitial lung disease and ANCA-associated vasculitis: a retrospective observational cohort study . Rheumatology (Oxford) 2011 ; 50 ( 11 ): 2035 - 43 . doi: 10.1093/rheumatology/ker236 https://dx.doi.org/10.1093/rheumatology/ker236 . DOI: 10.1093/rheumatology/ker236 http://doi.org/10.1093/rheumatology/ker236

Li ZY , Chang DY , Zhao MH , et al . Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated vasculitis: a study of 439 cases in a single Chinese center . Arthritis Rheumatol 2014 ; 66 ( 7 ): 1920 - 6 . doi: 10.1002/art.38621 https://dx.doi.org/10.1002/art.38621 . DOI: 10.1002/art.38621 http://doi.org/10.1002/art.38621 http://doi.wiley.com/10.1002/art.v66.7 http://doi.wiley.com/10.1002/art.v66.7

Kadura S , Raghu G . Antineutrophil cytoplasmic antibody-associated interstitial lung disease: a review . Eur Respir Rev 2021 ; 30 ( 162 ): 210123 . doi: 10.1183/16000617.0123-2021 https://dx.doi.org/10.1183/16000617.0123-2021 . DOI: 10.1183/16000617.0123-2021 http://doi.org/10.1183/16000617.0123-2021

Sebastiani M , Manfredi A , Vacchi C , et al . Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis . Clin Exp Rheumatol 2020 ; 38 ( 2 ): 221 - 31 .

Hervier B , Pagnoux C , Agard C , et al . Pulmonary fibrosis associated with ANCA-positive vasculitides. Retrospective study of 12 cases and review of the literature . Ann Rheum Dis 2009 ; 68 ( 3 ): 404 - 7 . doi: 10.1136/ard.2008.096131 https://dx.doi.org/10.1136/ard.2008.096131 . DOI: 10.1136/ard.2008.096131 http://doi.org/10.1136/ard.2008.096131

Tzelepis GE , Kokosi M , Tzioufas A , et al . Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis . Eur Respir J 2010 ; 36 ( 1 ): 116 - 21 . doi: 10.1183/09031936.00110109 https://dx.doi.org/10.1183/09031936.00110109 . DOI: 10.1183/09031936.00110109 http://doi.org/10.1183/09031936.00110109

Comarmond C , Crestani B , Tazi A , et al . Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature . Medicine (Baltimore) 2014 ; 93 ( 24 ): 340 - 9 . doi: 10.1097/MD.0000000000000217 https://dx.doi.org/10.1097/MD.0000000000000217 . DOI: 10.1097/MD.0000000000000217 http://doi.org/10.1097/MD.0000000000000217 https://journals.lww.com/00005792-201411040-00003 https://journals.lww.com/00005792-201411040-00003

Fernandez Casares M , Gonzalez A , Fielli M , et al . Microscopic polyangiitis associated with pulmonary fibrosis . Clin Rheumatol 2015 ; 34 ( 7 ): 1273 - 7 . doi: 10.1007/s10067-014-2676-1 https://dx.doi.org/10.1007/s10067-014-2676-1 . DOI: 10.1007/s10067-014-2676-1 http://doi.org/10.1007/s10067-014-2676-1

Huang H , Wang YX , Jiang CG , et al . A retrospective study of microscopic polyangiitis patients presenting with pulmonary fibrosis in China . BMC Pulm Med 2014 ; 14 : 8 . doi: 10.1186/1471-2466-14-8 https://dx.doi.org/10.1186/1471-2466-14-8 . DOI: 10.1186/1471-2466-14-8 http://doi.org/10.1186/1471-2466-14-8

Hozumi H , Kono M , Hasegawa H , et al . Clinical significance of interstitial lung disease and its acute exacerbation in microscopic polyangiitis . Chest 2021 ; 159 ( 6 ): 2334 - 45 . doi: 10.1016/j.chest.2021.01.083 https://dx.doi.org/10.1016/j.chest.2021.01.083 . DOI: 10.1016/j.chest.2021.01.083 http://doi.org/10.1016/j.chest.2021.01.083

Kagiyama N , Takayanagi N , Kanauchi T , et al . Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis . BMJ Open Respir Res 2015 ; 2 ( 1 ): e000058 . doi: 10.1136/bmjresp-2014-000058 https://dx.doi.org/10.1136/bmjresp-2014-000058 . DOI: 10.1136/bmjresp-2014-000058 http://doi.org/10.1136/bmjresp-2014-000058 https://bmjopenrespres.bmj.com/lookup/doi/10.1136/bmjresp-2014-000058 https://bmjopenrespres.bmj.com/lookup/doi/10.1136/bmjresp-2014-000058

Zhou P , Li Z , Gao L , et al . Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients . BMC Pulm Med 2022 ; 22 ( 1 ): 35 . doi: 10.1186/s12890-022-01829-y https://dx.doi.org/10.1186/s12890-022-01829-y . DOI: 10.1186/s12890-022-01829-y http://doi.org/10.1186/s12890-022-01829-y

Sarica SH , Dhaun N , Sznajd J , et al . Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study . Rheumatology (Oxford) 2020 ; 59 ( 10 ): 3014 - 22 . doi: 10.1093/rheumatology/keaa070 https://dx.doi.org/10.1093/rheumatology/keaa070 . DOI: 10.1093/rheumatology/keaa070 http://doi.org/10.1093/rheumatology/keaa070

Lauque D , Cadranel J , Lazor R , et al . Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature . Medicine (Baltimore) 2000 ; 79 ( 4 ): 222 - 33 . doi: 10.1097/00005792-200007000-00003 https://dx.doi.org/10.1097/00005792-200007000-00003 . DOI: 10.1097/00005792-200007000-00003 http://doi.org/10.1097/00005792-200007000-00003 http://journals.lww.com/00005792-200007000-00003 http://journals.lww.com/00005792-200007000-00003

Matsuda S , Kotani T , Suzuka T , et al . Evaluation of poor prognostic factors of respiratory related death in microscopic polyangiitis complicated by interstitial lung disease . Sci Rep 2021 ; 11 ( 1 ): 1490 . doi: 10.1038/s41598-021-81311-7 https://dx.doi.org/10.1038/s41598-021-81311-7 . DOI: 10.1038/s41598-021-81311-7 http://doi.org/10.1038/s41598-021-81311-7

Kida T , Tanaka T , Yokota I , et al . Association between preexisting lung involvements and the risk of diffuse alveolar hemorrhage in patients with microscopic polyangiitis: a multi-center retrospective cohort study . Mod Rheumatol 2020 ; 30 ( 2 ): 338 - 44 . doi: 10.1080/14397595.2019.1601855 https://dx.doi.org/10.1080/14397595.2019.1601855 . DOI: 10.1080/14397595.2019.1601855 http://doi.org/10.1080/14397595.2019.1601855

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