Doumat, George

Abstract Rationale Gastroesophageal reflux disease (GERD) is a common comorbidity in non-cystic fibrosis bronchiectasis (NCFB), yet its impact on clinical outcomes remains poorly defined. We sought to determine whether GERD is associated with worse clinical outcomes in patients with NCFB using a large, real-world database. Methods We conducted a retrospective cohort study using the TriNetX platform, identifying patients with NCFB (ICD-10 J47*) with and without concurrent GERD (ICD-10 K21*), excluding those with cystic fibrosis (ICD-10 E84*). Propensity score matching (PSM) was performed using 1:1 nearest neighbor matching without replacement, controlling for age, sex, race/ethnicity, obesity, socioeconomic risk factors, and tobacco use. Primary outcomes included pneumonia, bronchiectasis exacerbations, intensive care unit admission, mechanical ventilation, and mortality. Statistical analyses included risk ratios and Cox proportional hazards modeling for survival outcomes. Results Out of 421,710 patients with NCFB in the dataset from January 2000 to September 2025, 186,874 (44%) had a diagnosis of GERD. After propensity score matching, 179,753 patients with NCFB+GERD and 179,753 patients with NCFB-only were included (mean age 74.0±13.1 years, 58.8% female, 67.1% White). Baseline characteristics were well-balanced after matching. Median follow-up was approximately 2.5 years for both cohorts (898 vs 889 days; similar means and IQR), ensuring balanced observation time. Compared to NCFB-only, NCFB+GERD was associated with increased risks for mortality (risk ratio 1.04, 95% CI 1.02-1.05; p < 0.001), pneumonia (risk ratio 1.06, 95% CI 1.05-1.08; p < 0.001), bronchiectasis exacerbations (risk ratio 1.03, 95% CI 1.01-1.06; p = 0.006), and mechanical ventilation (risk ratio 1.14, 95% CI 1.10-1.18; p < 0.001). Intensive care unit admission rates were comparable between groups (risk ratio 1.00; p = 0.65). Conclusions In this large propensity score-matched analysis, concurrent GERD in NCFB is independently associated with increased mortality, pneumonia, bronchiectasis exacerbations, and mechanical ventilation requirements. These findings suggest GERD may represent a modifiable risk factor warranting aggressive management in NCFB patients. Study limitations include retrospective design, reliance on ICD-10 coding accuracy, and potential unmeasured confounders. Our results support systematic screening and treatment of GERD in NCFB, but whether targeted GERD management can modify the natural history of NCFB future investigation. This abstract is funded by: None

Abstract Background: Bronchiectasis is a recognized pulmonary manifestation of ANCA-associated vasculitides (AAV). Although positive AAV workup has been observed in patients with isolated airway diseases, without other systemic involvement, AAV workup is not routinely obtained in patients presenting with bronchiectasis. Patients with bronchiectasis and positive AAV workup may represent a distinct subgroup with unique characteristics and outcomes. Objectives: To establish a cohort of patients with bronchiectasis who also have a positive AAV workup (i.e., presence of ANCA by indirect immunofluorescence AND elevated antibodies to PR3 or MPO) and to describe their characteristics. METHODS: There were 944 patients across Mayo clinic sites with bronchiectasis (J47.9, J47.0 and J 47.1) who underwent AAV workup. Of these 315 (33.36%) had evidence of ANCA on immunofluorescence and an abnormal level of antibodies to PR3 or MPO. Chest CT scans were reviewed, and 118 patients were excluded because their pulmonary disease was mostly interstitial or had no clear bronchiectasis. Co-morbidities were evaluated using respective ICD-10 codes and respiratory cultures were collected. RESULTS: A total of 197 patients were identified with Bronchiectasis (76% female; mean age 66 years, BMI 25 kg/m2), 112 (56.8%) were diagnosed before antibody detection and 85 (43.1%) after. MPO (positive [>0.9] or equivocal [0.4-0.9]) was detected in 177 (89.8%) patients; PR3 (positive [>0.9] or equivocal [0.4-0.9]) in 34 (17.2%). P-ANCA and c-ANCA patterns occurred in 185 (94%) and 15 (4%) patients, respectively. The most common antigen-target/ANCA combinations were MPO/p-ANCA (177, 89.8%), PR3/p-ANCA (22, 11.2%), and PR3/c-ANCA (14, 7.1%). Comorbidities included asthma (66, 33.5%), COPD (58, 29.4%), GERD (64, 32.5%), hypothyroidism (56, 28.4%), and autoimmune/inflammatory conditions (e.g., rheumatoid arthritis [23, 11.7%], IBD [25, 12.7%]). Neurologic (42, 23.9%) and renal (25, 14.7%) manifestations occurred. Respiratory cultures (n=122) isolated yeast (57, 46.7%), Aspergillus (34, 27.9%), and Pseudomonas (30, 24.6%); Mycobacteria and other molds (e.g., Penicillium) each appeared in 23-24 patients (∼19%). Conclusion: This work identifies a cohort of patients with bronchiectasis who also have a positive AAV workup, mostly MPO/p-ANCA. While AAV workup is not routine for patients presenting for bronchiectasis evaluation, some patients in this cohort had primarily airway disease with an abnormal AAV workup, in the absence of other common manifestations of AAV. Further research on this cohort will be conducted to determine whether these patients represent a distinct group with unique characteristics, treatment patterns, and outcomes.