Older Age, Infections Tied to Poor Outcomes in AAV with Lung Hemorrhage

Older Age, Infections Tied to Poor Outcomes in AAV with Lung Hemorrhage
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Outcomes for people with ANCA-associated vasculitis (AAV) who have an alveolar hemorrhage (bleeding in the lungs’ air sacs) are likely to be worse if they are age 65 or older, need respiratory support, or develop infections, a study reports.

The study, “Alveolar haemorrhage in ANCA-associated vasculitis: Long-term outcome and mortality predictors,” was published in the Journal of Autoimmunity.

Alveolar hemorrhage is one of the most severe manifestations of AAV. However, prior studies of such bleeding in AAV have been limited by small numbers of patients, making it difficult to definitively assess how such hemorrhages affect or predict patient outcomes.

Researchers in Italy aimed to identify likely predictors of poor outcomes, and to assess signs and symptoms that could help establish an early diagnosis and timely treatment.

A total of 106 patients, median age of 55, were diagnosed with an AAV-associated alveolar hemorrhage (AH) from 2007 to 2016. They were followed at one of 29 Italian centers for a mean of 37 months (3 years and one month) after hemorrhage onset. In most patients (71.7%), AH was diagnosed simultaneously with AAV.

Fifty-one of these patients had  microscopic polyangiitis (MPA), 49 had granulomatosis with polyangiitis  (GPA), and six eosinophilic granulomatosis with polyangiitis (EGPA); these are the three forms of vasculitis.

Over 72% of patients had renal complications, followed by cardiovascular manifestations in almost half (49.1%).

Upon diagnosis, 97 patients (92.4%) had anemia, 54 (51.9%) had hemoptysis (coughing blood) and 68 (66.7%) respiratory failure, 48 of whom needed respiratory support. Thirty one patients were hospitalized in the intensive care unit and 11 needed an approach called extracorporeal membrane oxygenation.

By 37 months after AH onset, 19 had died (17.9%), mostly due to active disease and infection, the study noted. Seven of the 19 died within three months of starting to hemorrhage, including four with multi-organ failure, two due to infections, and one due to both infections and the hemorrhage.

Older age, 65 and above, and a need for respiratory support at AH onset were predictors of mortality. But when the researchers excluded patients followed for about three months, infections were a greater predictive factor than respiratory support. In turn, cumulative dose of cyclophosphamide was the only protective parameter (the higher the dose, the lower the risk).

Neither the Revisited Five Factor Score of prognosis, or the Vasculits Activity Score version 3 of disease activity were able to accurately predict mortality after an AH, “meaning that in this particular subset of patients, dedicated tools are needed,” the researchers wrote.

All patients were treated with glucocorticoids (steroid hormones that can ease inflammation), most commonly methylprednisolone. Eighty (77.7%) received cyclophosphamide, 14 (13.5%) were given rituximab (sold as Rituxan, among others), 25 (24%) took both cyclophosphamide and rituximab, and 46 patients also underwent plasma exchange (plasmapheresis) therapy.

Rituximab is a monoclonal antibody that binds to CD20, a protein found on the surface of certain B-cells. The medication has been approved by the U.S. Food and Drug Administration (FDA) for two types of AAV: GPA and MPA. Plasma exchange involves replacing a person’s plasma, the largely colorless liquid portion of blood.

“We highlighted that outcome is strongly influenced by both factors that are an expression of intrinsic frailty [such as older age and infections], and factors that point to a more severe lung involvement (the need for respiratory support at onset),” the researchers wrote.

“As a consequence, treatment must be individualized and [kept] into account, alongside with AH severity, the patient’s baseline characteristics, frailty and risk of infection,” they added.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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