RATIONALE: Severe asthmatics suffer from a disease that is poorly understood and uncontrolled with traditional therapy. Although asthma was widely considered as a Th2-like disease, evidence that Th1 and Th17 patterns are contributing to severity and treatment-resistance in asthma is increasing. METHODS: We performed a retrospective review of medical records of consecutive patients with a diagnosis of “severe asthma” who underwent video-assisted thoracoscopic surgery (VATS) for lung biopsy. Medical records were searched for diagnoses of autoimmune diseases (AID), including ANCA-associated vasculitis, connective tissue disease, inflammatory bowel disease and others. Additionally, family history (FH) for AID and asthma and treatment with immunosuppressive drugs and response to those treatments were recorded. RESULTS: Thirty-nine patients who underwent VATS biopsy had a median age of 54 yrs (range 30-69). The overall median age at asthma onset was 26 yrs (range 1-65), 82 % were females and 59 % had a FH of asthma. All met severe asthma definitions by ATS/ERS guidelines and were on systemic corticosteroids (CS). 24 (62 %) severe asthmatics were classified as having a background of autoimmune disease (SA-AI): 16 patients (41 %) were diagnosed with AID (4 with undifferentiated systemic rheumatic disease, 4 systemic lupus erythematosus, 2 rheumatoid arthritis, 2 ulcerative colitis, 1 Sjögren's syndrome, 1 antiphospholipid syndrome, 1 eosinophilic granulomatosis with polyangitis, 1 diabetes mellitus type I). Additional 4 patients (10 %) had a positive FH of AID and 4 (10 %) a history of thyroid dysfunction (possible marker for AID). Median age at onset of asthma in SA-AI and SA patients was 29 (IQR 10-41) vs 13 yrs (IQR 3-42, p = 0.185), respectively, and time to progression to severe disease tends to be shorter in SA-AI with median time of 12 (IQR 3-25) vs 23 yrs (IQR 11-35, p = 0.066). All patients received immunosuppressive treatment (azathioprine 95 %, mycophenolate 54 %, methotrexate 15 %). Treatment response, as defined by overall impression of the attending physician, appeared better in patients with AID or FH of AID compared to SA patients with 23/8 vs 9/10 responders/non-responders, respectively (p = 0.054). CONCLUSION: More than 60 % of very severe CS dependent asthmatics undergoing VATS biopsies had a background of autoimmune disease. Those patients tend to have a more rapid progression to ATS-ERS defined severe disease. However, alternative immunosuppressants may be a more effective treatment in this subset of severe asthmatics, although the mechanisms for their efficacy remain unknown.
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