There was no significant difference in survival after controlling for age, sex, and baseline pulmonary function (hazard ratio, 0.84; 95%?CI, 0.39-1.80; em P /em ?= .65). Open in a separate window Figure?1 Kaplan-Meier curve comparing transplant-free survival in patients with idiopathic pulmonary fibrosis that are positive vs?negative for ANCA. patients with IPF were positive for ANCAs at the time of diagnosis in the discovery and replication cohorts, respectively. Among those positive for MPO antibodies, two of six (33%) in the discovery cohort and three of 12 (25%) in the replication cohort developed vasculitis. None of the patients who were PR3-positive developed vasculitis. Patients who were ANCA-positive were more likely to be women than patients who were ANCA-negative, and were more likely to have some ground-glass opacities on CT scan. In the combined cohort of 745 patients, median transplant-free survival was not significantly different in patients who were ANCA-positive vs?ANCA-negative (test as appropriate. Transplant-free survival between the two groups was visualized using Kaplan-Meier survival plots and compared using the log-rank test and Cox proportional hazards models (stratified by cohort), both unadjusted and adjusted for other baseline variables commonly associated with survival in IPF; these included age, sex, FVC %?predicted, and diffusing capacity of the lung for carbon monoxide %?predicted. Results Clinical Characteristics Among 353 patients with IPF in the discovery cohort, 14 (4.0%, 95%?CI, 2.2-6.5) were found to have ANCAs present at the time of study enrollment. Of the patients with ANCAs, eight of 14 (57%) had PR3 antibodies and?six of 14 (43%) had MPO antibodies. The proportion of patients with positive ANCAs was similar in the replication cohort (20 of 392 [5.1%]; 95%?CI, 3.1-7.8). Of these, two of 20 (10%) had PR3 antibodies, 12 of 20 (60%) had MPO antibodies, and six of 20 (30%) had nonspecific ANCA positivity (positive by immunofluorescence, but subsequent Diethyl oxalpropionate PR3 and MPO antibody testing negative). The comparison of clinical characteristics between patients with ANCA-positive and ANCA-negative IPF is summarized in Table?1. Diethyl oxalpropionate Compared with patients with ANCA-negative IPF, patients with ANCA-positive IPF were more likely to be?women in both cohorts (discovery cohort: 47.1%?vs?22.9%, ValueValueValueValue /th /thead Total No. with CT PLXNC1 scan scored31312UIP, definite or possiblea249 (79.6)9 (75.0).72Reticulation, moderate or severeb249 (79.6)8 (66.7).28Traction bronchiectasis present307 (98.1)12 (100.0) .99?Moderate or severeb195 (62.3)4 (33.3).07Honeycombing present211 (67.4)9 (75.0).76?Moderate or severeb33 (10.5)4 (33.3).04Fibrosis, cranial-caudal distribution.64?Diffuse14 (4.5)1 (8.3)?Lower288 (92.0)11 (91.7)?Middle or upper11 (3.5)0 (0.0)Fibrosis, axial distribution .99?Central2 (0.6)0 (0.0)?Diffuse23 (7.3)1 (8.3)?Peripheral288 (92.0)11 (91.7)Ground-glass opacity present29 (9.3)4 (33.3).02Consolidation present11 (3.5)0 (0.0) .99Nodules present2 (0.6)0 (0.0) .99Small airways disease present68 (97)4/4 (100) .99 Open in a separate window CT scans of the chest evaluated for UIP pattern and specific radiographic findings pertinent to interstitial lung disease. Values are No. (%) or as otherwise indicated. See Table?1 and ?and22 legends for expansion of abbreviations. aDefinite or possible UIP pattern vs?inconsistent with UIP pattern. bModerate or severe vs?mild or none. Histopathologic Features Eight patients with ANCA-positive IPF in the discovery cohort had lung biopsies, five of which were formally scored using a standardized data collection form. Ten patients with ANCA-positive IPF in the replication cohort had lung biopsies, and results were obtained from chart review and were not formally scored. Given the limited number of patients with lung biopsies, Diethyl oxalpropionate there were no statistical comparisons made between patients with ANCA-positive and ANCA-negative IPF. Summary of pathologic findings for patients with ANCA-positive IPF are included in Table?2. None of these patients had evidence of capillaritis or vasculitis on pathology. Treatment and Outcomes After a median follow-up time of 18.3?months by chart review, two of the six patients (33%) with MPO antibodies in the discovery cohort developed a clinical diagnosis of MPA, both at least 1 year after their diagnosis of IPF (Table?2). In the replication cohort, three of 12 patients (25%) with MPO antibodies subsequently developed clinical vasculitis (one developed MPA and two developed nonspecific ANCA-associated vasculitis) after a median follow-up of 10.5?months. Additionally, all patients who developed vasculitis in both the discovery and replication cohorts were women. The clinical manifestations of vasculitis seen in these patients were renal disease (three of five patients), mononeuritis multiplex (two of five patients), purpura (one of five patients), sinusitis (one of five patients), and inflammatory arthritis (one of five patients). None of the patients with PR3 or nonspecific ANCAs developed vasculitis during the follow-up period. As outlined in Table?2, the choice of pharmacologic treatment in the discovery cohort appears to be based largely on time of study enrollment. The three patients with ANCA-positive IPF enrolled before 2012, when the?results of the Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis trial had been published, were all recommended azathioprine, and most patients enrolled after this time were recommended antifibrotic agents alone.13 In the replication cohort, 15 of the 20 patients with ANCA-positive IPF received immunosuppressive medications, either with or without antifibrotic agents. Of the 15 patients who received immunosuppression, two were treated prior to the results of the Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis trial, eight were treated.