RATIONALE; Severe asthmatics suffer from a disease that is poorly understood and uncontrolled with traditional therapy. Although asthma was widety considered as a Th2·rike disease. evidence that Th t and Th 17 patterns are contributing to severity and ueatment· resistance In asthma is increasing. METHODS: We performed a retrospective review of medic.al rKords of consecutive patients W1th a d1a9nos1s of ·severe asthma• who underwent video-assisted thoracoscopic surgery (VATS) for lung biopsy. Medical records were searched for diagnoses of autofmmune diseases (AID), in duding ANCA·auoeiated vasculrt1s. connective tissue disease. innammatory bowel disease and others. Additionally, family history (FH) for AID and asthma and treatment with 1mmunosuppresslve drugs and response to those treatments were recorded. RESULTS: Thirty-nine patients who underwent VATS biopsy had a median age of S4 yrs (range 30-69). The overall median age at asthma onset was 26 yrs (range 1 65), 82 Iii!> were females and 59 ~ had a FH of asthma. All met severe asthma definitions by ATSIERS guidelines and were on systemic corticosteroids ccsi 24 (62 Clti) severe asthmatics were dassified as having a background of autoimmune disease (SA·AI): 16 patten ts (41 ~} were diagnosed W1lh AID (4 W1th und1ffetentiated systemk: rheumatic disease. 4 systemic lupus etythematosus. 2 rheumatoid arthritis. 2 ulcerative colitis. 1 Sjogren's syndrome, 1 antiphospholipid syndrome, 1 eosinophilic granulomatosis with polyangitlS, 1 diabetes mellitus type I). Addrttonal 4 patients (10 ~) had a positive FH of AID and 4 (10 %) a history of thyroid dysfunction (poss.ible marker (or 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 1n SA-Al with median tme of t 2 (IQR 3-25) vs 23 yrs (IQR 11-35. p - 0.066). All patents rece ived 1mmunosuppress1ve treatment (azathioprine 95 ' mycophenolate 54 Cit>. methottexate 1 S citi). Treatment response, as defined by overall impres51on of the anend1ng physician, appeared better in patients with AID or FH of AID compared to SA patients with 2318 vs 9/1 O responders/non responders. respectively (p 0.054). CONCLUSION: M<> of very severe CS dependent asthmatics undergouig VA TS biopsies had a background of autoimmune disease. Those patients tend to have a more rapid progression to ATS ERS defined severe disease. HO\vevet, alternative m muoosuppressants may be a more effective treatment in this subset of sevefe asthmatics. although the mechanisms for their efficacy remain unknown.
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