Dataset Information

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

ABSTRACT:

Background

Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases.

Methods

French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016.

Results

One hundred four patients (54% of men) with median age of 56 [32-68] years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR [95%CI] 0.97 [0.96-0.99] per 10?years, p?ConclusionDAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.

SUBMITTER: Mirouse A

PROVIDER: S-EPMC7236262 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

Mirouse Adrien A Parrot Antoine A Audigier Vincent V Demoule Alexandre A Mayaux Julien J Géri Guillaume G Mariotte Eric E Bréchot Nicolas N de Prost Nicolas N Vautier Mathieu M Neuville Mathilde M Bigé Naïke N de Montmollin Etienne E Cacoub Patrice P Resche-Rigon Matthieu M Cadranel Jacques J Saadoun David D

Critical care (London, England) 20200518 1

<h4>Background</h4>Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases.<h4>Methods</h4>French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016.<h4>Results</h4>One hundred four patients (54% of ...[more]

PMID: 32423434

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Project description:BackgroundIncreasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression of miRNAs and increased formation of neutrophil extracellular traps (NETs) and apoptosis participate in autoimmune-mediated diffuse alveolar hemorrhage (DAH), mostly associated with pulmonary capillaritis in systemic lupus erythematosus (SLE) patients. In particular, besides the inhibition of apoptosis, miR-146a can control innate and acquired immune responses, and regulate the toll-like receptor pathway through targeting TRAF6 to reduce the expression of pro-inflammatory cytokines/chemokines like IL-8, a NETosis inducer.MethodsExpression of miR-146a, TRAF6 and NETs were examined in peripheral blood neutrophils (PBNs) and lung tissues from SLE-associated DAH patients, and in neutrophils and pristane-induced DAH lung tissues from C57BL/6 mice. To assess NETs formation, we examined NETosis-related DNAs morphology and crucial mediators including protein arginine deiminase 4 and citrullinated Histone 3. Expression of miR-146a and its endogenous RNA SNHG16 were studied in HL-60 promyelocytic cells and MLE-12 alveolar cells during NETosis and apoptosis processes, respectively. MiR-146a-overexpressed and CRISPR-Cas13d-mediated SNHG16-silenced HL-60 cells were investigated for NETosis. MiR-146a-overexpressed MLE-12 cells were analyzed for apoptosis. Pristane-injected mice received intra-pulmonary miR-146a delivery to evaluate therapeutic efficacy in DAH.ResultsIn DAH patients, there were down-regulated miR-146a levels with increased TRAF6 expression and PMA/LPS-induced NETosis in PBNs, and down-regulated miR-146a levels with increased TRAF6, high-mobility group box 1 (HMGB1), IL-8, NETs and apoptosis expression in lung tissues. HMGB1-stimulated mouse neutrophils had down-regulated miR-146a levels with increased TRAF6, IL-8 and NETs expression. PMA-stimulated HL-60 cells had down-regulated miR-146a levels with enhanced NETosis. MiR-146a-overexpressed or SNHG16-silenced HL-60 cells showed reduced NETosis. Apoptotic MLE-12 cells had down-regulated miR-146a expression and increased HMGB1 release, while miR-146a-overexpressed MLE-12 cells showed reduced apoptosis and HMGB1 production. There were down-regulated miR-146a levels with increased TRAF6, HMGB1, IL-8, NETs and apoptosis expression in mouse DAH lung tissues. Intra-pulmonary miR-146a delivery could suppress DAH by reducing TRAF6, IL-8, NETs and apoptosis expression.ConclusionsOur results demonstrate firstly down-regulated pulmonary miR-146a levels with increased TRAF6 and IL-8 expression and NETs and apoptosis formation in autoimmune-mediated DAH, and implicate a therapeutic potential of intra-pulmonary miR-146a delivery.

Project description:Diffuse alveolar hemorrhage (DAH) can be caused by various conditions, categorized as autoimmune and non-autoimmune. Immunofactor-mediated vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, and antiphospholipid antibody syndrome, are common autoimmune causes. Non-autoimmune factors include infectious or toxic exposures and neoplastic conditions. The diagnosis of DAH, resulting from excessive catecholamine release from an adrenal pheochromocytoma or extra-adrenal paraganglioma, can present diagnostic challenges and necessitate prompt treatment. In this report, we present a case of pheochromocytoma that manifested as an adrenal incidentaloma (diagnosed during the management of sudden-onset DAH after cholecystectomy). Case report: A 39-year-old female patient with adrenal incidentaloma developed DAH following a cholecystectomy procedure, presenting with sudden-onset hemoptysis and dyspnea. Administration of glucocorticoids, known to precipitate pheochromocytoma crisis (PCC), was required before the cause was determined. Intubation and mechanical ventilation were necessary due to persistent hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). The patient in this case experienced two epidoses of PCC while she was on mechanical ventilation. Subsequent work-up revealed a 26 × 25 mm left adrenal adenoma with hormonal confirmation of catecholamine hypersecretion. A laparoscopic adrenalectomy was done eight months later to excise the left adrenal gland. Subsequent examination of the tissue revealed pheochromocytoma, thereby validating the initial diagnosis. Conclusion: Adrenal incidentalomas may be pheochromocytomas (adrenal incidentalomas can manifest as pheochromocytomas), even without adrenergic symptoms. It is recommended that adrenal incidentalomas undergo evaluation for pheochromocytoma before undergoing invasive surgery or receiving corticosteroid treatment. When considering potential causes of DAH without further elucidation, including a pheochromocytoma or paraganglioma (PPGLs) in the differential diagnosis is important.

Dataset Information

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

Background

Methods

Results

Publications

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

Similar Datasets

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