Advertisement

Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis

Published:February 08, 2021DOI:https://doi.org/10.1016/j.chest.2021.01.083

      Background

      Presence of interstitial lung disease (ILD) is thought to be associated with mortality in microscopic polyangiitis (MPA); however, evidence on MPA-ILD remains lacking. Acute exacerbation (AE) refers to rapidly progressive, fatal respiratory deterioration that may develop in patients with various ILDs. No study has investigated the clinical significance of AE in MPA-ILD.

      Research Question

      We aimed to determine the clinical picture and prognostic factors, the incidence of AE, and the risk factors in patients with MPA-ILD.

      Study Design and Methods

      Eighty-four consecutive patients with MPA-ILD and 95 patients with MPA-non-ILD were analyzed. We also compared 80 patients with MPA-ILD and 80 patients with idiopathic interstitial pneumonia without myeloperoxidase-antineutrophil cytoplasmic antibody positivity (ILD alone), who were matched for age, sex, and chest high-resolution CT scan pattern.

      Results

      The MPA-ILD group had a higher frequency of men and smokers and was associated with higher mortality than the MPA-non-ILD group. The matched MPA-ILD group had a higher mortality rate than the matched ILD alone group. There was no significant difference in AE incidence between the matched MPA-ILD and ILD alone groups (1-year AE cumulative incidence rate, 7.5% and 5.2%, respectively; P = .75). In the MPA-ILD group, a lower percent predicted FVC (%FVC) was independently associated with a higher mortality rate (hazard ratio [HR], 0.96 per 1% increase; P < .01) and a higher AE incidence rate (HR, 0.96 per 1% increase; P = .01). On multivariable Cox regression analysis with time-dependent covariates, developing AE during their clinical course was strongly associated with shorter survival (HR, 17.1; P < .001).

      Interpretation

      MPA-ILD represented a distinct phenotype with poor prognosis. Lower %FVC was an independent prognostic factor. Patients with lower %FVC had a risk of developing AE, which was a strong prognostic determinant. The specific management for MPA-ILD and AE should be established.

      Key Words

      Abbreviations:

      AAV (ANCA-associated vasculitide), AE (acute exacerbation), ANCA (antineutrophil cytoplasmic antibody), CS (corticosteroid), DAH (diffuse alveolar hemorrhage), GPA (granulomatosis with polyangiitis), HR (hazard ratio), HRCT (high-resolution CT), ILD (interstitial lung disease), IPF (idiopathic pulmonary fibrosis), KL-6 (Krebs von den Lungen-6), MPA (microscopic polyangiitis), MPO (myeloperoxidase), %FVC (percent predicted FVC), PR3 (proteinase 3), RA-ILD (rheumatoid arthritis-associated ILD), UIP (usual interstitial pneumonia)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jennette J.C.
        • Falk R.J.
        • Bacon P.A.
        • et al.
        2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.
        Arthritis Rheum. 2013; 65: 1-11
        • Watts R.
        • Lane S.
        • Hanslik T.
        • et al.
        Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies.
        Ann Rheum Dis. 2007; 66: 222-227
        • Lane S.E.
        • Watts R.A.
        • Shepstone L.
        • Scott D.G.
        Primary systemic vasculitis: clinical features and mortality.
        QJM. 2005; 98: 97-111
        • Mukhtyar C.
        • Flossmann O.
        • Hellmich B.
        • et al.
        Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.
        Ann Rheum Dis. 2008; 67: 1004-1010
        • Jardel S.
        • Puechal X.
        • Le Quellec A.
        • et al.
        Mortality in systemic necrotizing vasculitides: a retrospective analysis of the French Vasculitis Study Group registry.
        Autoimmun Rev. 2018; 17: 653-659
        • Lyons P.A.
        • Rayner T.F.
        • Trivedi S.
        • et al.
        Genetically distinct subsets within ANCA-associated vasculitis.
        N Engl J Med. 2012; 367: 214-223
        • Cornec D.
        • Cornec-Le Gall E.
        • Fervenza F.C.
        • Specks U.
        ANCA-associated vasculitis - clinical utility of using ANCA specificity to classify patients.
        Nat Rev Rheumatol. 2016; 12: 570-579
        • Chen M.
        • Kallenberg C.G.
        ANCA-associated vasculitides--advances in pathogenesis and treatment.
        Nat Rev Rheumatol. 2010; 6: 653-664
        • Greco A.
        • De Virgilio A.
        • Rizzo M.I.
        • et al.
        Microscopic polyangiitis: advances in diagnostic and therapeutic approaches.
        Autoimmun Rev. 2015; 14: 837-844
        • Tzelepis G.E.
        • Kokosi M.
        • Tzioufas A.
        • et al.
        Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis.
        Eur Respir J. 2010; 36: 116-121
        • Arulkumaran N.
        • Periselneris N.
        • Gaskin G.
        • et al.
        Interstitial lung disease and ANCA-associated vasculitis: a retrospective observational cohort study.
        Rheumatology (Oxford). 2011; 50: 2035-2043
        • Schirmer J.H.
        • Wright M.N.
        • 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: 71-79
        • Maillet T.
        • Goletto T.
        • Beltramo G.
        • et al.
        Usual interstitial pneumonia in ANCA-associated vasculitis: a poor prognostic factor.
        J Autoimmun. 2020; 106: 102338
        • 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: 713-723
        • Collard H.R.
        • Ryerson C.J.
        • Corte T.J.
        • et al.
        Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report.
        Am J Respir Crit Care Med. 2016; 194: 265-275
        • Raghu G.
        • Remy-Jardin M.
        • Myers J.L.
        • et al.
        Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT Clinical Practice Guideline.
        Am J Respir Crit Care Med. 2018; 198: e44-e68
        • Suda T.
        • Kaida Y.
        • Nakamura Y.
        • et al.
        Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases.
        Respir Med. 2009; 103: 846-853
        • Park I.N.
        • Kim D.S.
        • Shim T.S.
        • et al.
        Acute exacerbation of interstitial pneumonia other than idiopathic pulmonary fibrosis.
        Chest. 2007; 132: 214-220
        • Hozumi H.
        • Nakamura Y.
        • Johkoh T.
        • et al.
        Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study.
        BMJ Open. 2013; 3e003132
        • Jennette J.C.
        • Falk R.J.
        • Andrassy K.
        • et al.
        Nomenclature of systemic vasculitides. Proposal of an international consensus conference.
        Arthritis Rheum. 1994; 37: 187-192
        • Hozumi H.
        • Oyama Y.
        • Yasui H.
        • et al.
        Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idiopathic interstitial pneumonias.
        PLoS One. 2018; 13e0199659
        • Liu G.Y.
        • Ventura I.B.
        • Achtar-Zadeh N.
        • et al.
        Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in North American patients with idiopathic pulmonary fibrosis.
        Chest. 2019; 156: 715-723
        • 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: 338-344
        • Casian A.
        • Jayne D.
        Management of alveolar hemorrhage in lung vasculitides.
        Semin Respir Crit Care Med. 2011; 32: 335-345
        • Guillevin L.
        • Lhote F.
        • Gayraud M.
        • et al.
        Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.
        Medicine. 1996; 75: 17-28
        • Furuta S.
        • Chaudhry A.N.
        • Hamano Y.
        • et al.
        Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan.
        J Rheumatol. 2014; 41: 325-333
        • Suzuki A.
        • Sakamoto S.
        • Kurosaki A.
        • et al.
        Chest high-resolution CT findings of microscopic polyangiitis: a Japanese first nationwide prospective cohort study.
        AJR Am J Roentgenol. 2019; 213: 104-114
        • Shi J.
        • Shen Q.
        • Chen X.M.
        • Du X.G.
        Clinical characteristics and outcomes in microscopic polyangiitis patients with renal involvement: a study of 124 Chinese patients.
        BMC Nephrol. 2019; 20: 339
        • Corral-Gudino L.
        • Borao-Cengotita-Bengoa M.
        • Del Pino-Montes J.
        • Lerma-Márquez J.L.
        Overall survival, renal survival and relapse in patients with microscopic polyangiitis: a systematic review of current evidence.
        Rheumatology (Oxford). 2011; 50: 1414-1423
        • Alba M.A.
        • Flores-Suarez L.F.
        • Henderson A.G.
        • et al.
        Interstital lung disease in ANCA vasculitis.
        Autoimmun Rev. 2017; 16: 722-729
        • Noble P.W.
        • Albera C.
        • Bradford W.Z.
        • et al.
        Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.
        Lancet. 2011; 377: 1760-1769
        • Richeldi L.
        • du Bois R.M.
        • Raghu G.
        • et al.
        Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.
        N Engl J Med. 2014; 370: 2071-2082
        • Flaherty K.R.
        • Wells A.U.
        • Cottin V.
        • et al.
        Nintedanib in progressive fibrosing interstitial lung diseases.
        N Engl J Med. 2019; 381: 1718-1727
        • Distler O.
        • Highland K.B.
        • Gahlemann M.
        • et al.
        Nintedanib for systemic sclerosis-associated interstitial lung disease.
        N Engl J Med. 2019; 380: 2518-2528
        • Maher T.M.
        • Corte T.J.
        • Fischer A.
        • et al.
        Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial.
        Lancet Respir Med. 2020; 8: 147-157
        • Ley B.
        • Ryerson C.J.
        • Vittinghoff E.
        • et al.
        A multidimensional index and staging system for idiopathic pulmonary fibrosis.
        Ann Intern Med. 2012; 156: 684-691
        • Winstone T.A.
        • Assayag D.
        • Wilcox P.G.
        • et al.
        Predictors of mortality and progression in scleroderma-associated interstitial lung disease: a systematic review.
        Chest. 2014; 146: 422-436
        • Solomon J.J.
        • Chung J.H.
        • Cosgrove G.P.
        • et al.
        Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease.
        Eur Respir J. 2016; 47: 588-596
        • Fujisawa T.
        • Hozumi H.
        • Kono M.
        • et al.
        Prognostic factors for myositis-associated interstitial lung disease.
        PLoS One. 2014; 9e98824
        • Kamiya Y.
        • Fujisawa T.
        • Kono M.
        • et al.
        Prognostic factors for primary Sjogren's syndrome-associated interstitial lung diseases.
        Respir Med. 2019; 159: 105811
        • Kolb M.
        • Bondue B.
        • Pesci A.
        • et al.
        Acute exacerbations of progressive-fibrosing interstitial lung diseases.
        Eur Respir Rev. 2018; 27
        • Leuschner G.
        • Behr J.
        Acute exacerbation in interstitial lung disease.
        Front Med (Lausanne). 2017; 4: 176
        • Birnbaum J.
        • Danoff S.
        • Askin F.B.
        • Stone J.H.
        Microscopic polyangiitis presenting as a "pulmonary-muscle" syndrome: is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?.
        Arthritis Rheum. 2007; 56: 2065-2071