Chest
Recent Advances in Chest MedicineAntineutrophil Cytoplasmic Antibody-Associated Vasculitides and Respiratory Disease
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In Vitro and In Vivo Models Studying the Pathogenic Role of ANCAs in Vasculitis
The close clinical association between MPO-ANCA and PR3-ANCA and AAV, together with evidence from in vitro and animal models,3, 5 suggests that they play a critical role in the pathogenesis of vascular damage in patients with AAV. ANCA antigens are mainly located within the cytoplasmic granules of resting neutrophils, “sheltered” from circulating ANCAs. However, when neutrophils are primed by tumor necrosis factor (TNF)-α, other cytokines, or microbial products, MPO and PR3 traffic to the
Clinical Forms of Lung Disease in AAV
Table 2 shows the spectrum of respiratory abnormalities found in patients with AAV. The recent European League Against Rheumatism recommendations27 for the management of primary small- and medium-vessel vasculitis classified AAV in different disease patterns, according to the extension and severity of the disease. These patterns were localized, (upper respiratory tract disease, lower respiratory tract disease, or both with no other systemic involvement or constitutional symptoms), early
Prognosis of Pulmonary Complications of AAV
AAV is potentially life threatening. Although outcomes differ, untreated NGV and MPA are normally rapidly progressive and fatal. MPA mortality is highest in the first year after diagnosis, whereas NGV mortality increases progressively, perhaps reflecting the nature of the underlying disease.37 When glucocorticoids and other immunosuppressants are administered, patient survival improves dramatically, and > 90% of patients achieve remission at 6 months.38 However, relapse rates remain at around
Treating Pulmonary Complications
Table 3 shows the therapeutic options for AAV and indications according to the results of clinical trials. Therapy with glucocorticoids in combination with other immunosuppressants, such as cyclophosphamide or methotrexate, are the current mainstay of AAV treatment.42 Cotrimoxazole therapy has shown benefit when coadministered with the standard immunosuppressant therapy for remission maintenance of patients with NGV and upper respiratory tract disease.48
The therapeutic options for pulmonary
Conclusions
Pulmonary involvement in patients with AAV is frequent. Depending on the nature of the lesions (nodules, infiltrates, or alveolar hemorrhage), patients may require different therapeutic approaches. In addition to glucocorticoids and other immunosuppressant agents, biological agents are emerging as potential therapies in refractory cases, although only rituximab and infliximab have been trialed with apparent initial clinical success. The results of ongoing and concluded trials are eagerly
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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Funding/Support: This study was in part supported by the Ministerio de Educación y Ciencia and Fondo Europeo de Desarrollo Regional (SAF 08/04328) and Marató TV3 (06/0710).
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