Microscopic polyangiitis presenting as a “pulmonary‐muscle” syndrome: Is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?

Birnbaum, Julius; Danoff, Sonye K.; Askin, Frederic B.; Stone, John H.

doi:10.1002/art.22633

Cited by 75 publications

(44 citation statements)

References 23 publications

(20 reference statements)

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“…Previous studies demonstrated that patients with AAV may have subclinical alveolar hemorrhage (9,39), which may cause subsequent pulmonary fibrosis in MPA (40). However, the patients with clinically apparent DAH in our study were less likely to show a reticular pattern.…”

Section: Discussioncontrasting

confidence: 62%

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

Yamagata

Ikeda

Tsushima

et al. 2016

Arthritis & Rheumatology

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Objective. To determine the prevalence of lung abnormalities on chest computed tomography (CT) in patients with microscopic polyangiitis (MPA), to assess the responsiveness of such abnormalities to initial treatment, and to assess associations between these abnormalities and patient and disease characteristics and mortality.Methods. We retrospectively identified 167 consecutive hospital-based patients with MPA in 3 hospitals in Japan. We longitudinally collected clinical information for 150 of these patients, for whom CT images obtained before treatment were available. We then determined the presence of 22 imaging components of lung abnormalities in these patients.Results. The vast majority of patients (97%) had at least 1 lung abnormality on chest CT images, including interstitial lung lesions (66%), airway lesions (66%), pleural lesions (53%), and emphysematous lesions (37%). In multivariate analyses, ground-glass opacity was associated with the Birmingham Vasculitis Activity Score, whereas 3 of 4 airway lesions were associated with myeloperoxidase-antineutrophil cytoplasmic antibodies. Latent class analysis identified a distinct group of patients with airwaypredominant lung lesions. Airway lesions such as bronchiolitis and bronchovascular bundle thickening were among the components that showed improvement within 3 months of the initial treatment. An idiopathic pulmonary fibrosis pattern was the only chest CT variable that was independently associated with shorter survival.Conclusion. Abnormalities in a wide range of anatomic areas, including the whole airway, can be identified in the lungs of patients with MPA before treatment. The prevalence, clustering patterns, and responsiveness to treatment of individual lung abnormalities provide groundwork for informing future studies to understand the pathophysiology of MPA.Microscopic polyangiitis (MPA) is a necrotizing systemic vasculitis that affects small to medium-sized vessels. In MPA, immune deposits on the vessel wall are usually absent, and serum antineutrophil cytoplasmic antibodies (ANCAs) are frequently present. MPA shares these

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Section: Discussioncontrasting

confidence: 62%

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

Yamagata

Ikeda

Tsushima

et al. 2016

Arthritis & Rheumatology

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“…Recurrent occult alveolar haemorrhage has been suggested as a putative mechanism leading to fibrosis, in a manner similar to that described for pulmonary fibrosis in patients with idiopathic haemosiderosis and haemoptysis [6,22]. Subclinical alveolar haemorrhage is frequently detected in patients with ANCA-associated vasculitides and pulmonary disease [23].…”

Section: Discussionmentioning

confidence: 93%

“…Diffuse alveolar haemorrhage secondary to pulmonary capillaritis is the most frequent manifestation of respiratory involvement, expressed clinically as haemoptysis, dyspnoea and anaemia [2,3]. Recently, case reports or small patient series [4][5][6][7][8][9][10][11][12][13][14][15] have also described pulmonary fibrosis in MPA and raised the question that pulmonary fibrosis may also be an important clinical manifestation of the disease. However, the precise prevalence of pulmonary fibrosis and its impact on patient survival remain largely unknown.…”

mentioning

confidence: 99%

Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis

Tzelepis¹,

Kokosi²,

Tzioufas³

et al. 2009

European Respiratory Journal

140

150

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We sought to determine the type of pulmonary involvement in microscopic polyangiitis (MPA), primarily focusing on pulmonary fibrosis (PF), its prevalence, temporal relationship with other disease manifestations and outcome.33 patients (16 males) with biopsy proven perinuclear anti-neutrophilic cytoplasmic antibodypositive MPA (age 63.5 yrs) participated in the study. Pulmonary involvement was assessed using standard methods, including radiographic imaging (chest radiographs and high-resolution computed tomography), pulmonary function testing, bronchoscopy and bronchoalveolar lavage, and, if indicated, lung biopsy. All-cause mortality was analysed by the Kaplan-Meier method and was compared between MPA patients with and without PF.At the time of diagnosis, renal involvement was detected in all patients, with renal biopsies being consistent with segmental necrotising glomerulonephritis in all patients. The most common respiratory symptom was haemoptysis, which was found in nine (27%) patients. PF was present in 12 (36%) patients at the time of diagnosis, whereas one patient developed PF while on therapy ,10 yrs after disease diagnosis. In seven patients with PF, respiratory symptoms related to fibrosis preceded other disease manifestations by a median (range) period of 13 (5-120) months. Patients were followed up for a period of 38¡30 months. Presence of PF was associated with increased mortality (p50.02), with six deaths occurring in the fibrotic group and one in the nonfibrotic group. In the fibrotic group most deaths were related to PF.PF occurs frequently in MPA, may precede other disease manifestations by a variable length of time and has a poor prognosis.

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“…Classical pulmonary involvement consists of alveolar haemorrhage secondary to pulmonary capillaritis [1,2]. Pulmonary fibrosis is also a potentially severe manifestation of MPA, but mild pulmonary fibrosis is significantly associated with an increased rate of mortality [2][3][4]. Although pulmonary fibrosis in MPA might result from iterative episodes of alveolar haemorrhage, half of patients with pulmonary fibrosis have no history of haemoptysis and pulmonary fibrosis can be the initial manifestation of the disease, sometimes several years prior to the diagnosis of MPA [2,5].…”

mentioning

confidence: 99%

The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis

Guilpain¹,

Chéreau²,

Goulvestre³

et al. 2010

European Respiratory Journal

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Lung fibrosis is considered a severe manifestation of microscopic polyangiitis (MPA). Antimyeloperoxidase (anti-MPO) antibodies in MPA patients' sera can activate MPO and lead to the production of reactive oxygen species (ROS). While high levels of ROS are cytotoxic, low levels can induce fibroblast proliferation. Therefore, we hypothesised that the oxidative stress induced by anti-MPO antibodies could contribute to lung fibrosis.24 MPA patients (45 sera) were enrolled in the study, including nine patients (22 sera) with lung fibrosis. Serum advanced oxidation protein products (AOPP), MPO-induced hypochlorous acid (HOCl) and serum-induced fibroblast proliferation were assayed.AOPP levels, MPO-induced HOCl production and serum-induced fibroblast proliferation were higher in patients than in healthy controls (p,0.0001, p50.0001 and p50.0005, respectively). Increased HOCl production was associated with active disease (p50.002). Serum AOPP levels and serum-induced fibroblast proliferation were higher in patients with active MPA and lung fibrosis (p,0.0001). A significant linear relationship between fibroblast proliferation, AOPP levels and HOCl production was observed only in patients with lung fibrosis.Oxidative stress, in particular the production of HOCl through the interaction of MPO with anti-MPO antibodies, could trigger the fibrotic process observed in MPA.

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Microscopic polyangiitis presenting as a “pulmonary‐muscle” syndrome: Is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?

Cited by 75 publications

References 23 publications

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

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

Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis

The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis

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