Labban, M. El

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.

Abstract RATIONALE: Absolute Blood Eosinophil Counts (BEC) in bronchiectasis patients offer insights into inflammatory patterns and potential treatments. In non-cystic fibrosis bronchiectasis (NCFB), BEC≥300 cells/μL characterizes Eosinophilic Bronchiectasis (EB), a type-2 inflammation endotype estimated in 20% of patients. Guidance on BEC assessment strategy (i.e., number, frequency and timing of BEC≥300 defining this endotype) is unclear. We hypothesize that EB incidence varies by BEC≥300 assessment strategy. We also investigate eosinophilic inflammation in CF for comparison. Objectives: Assess BEC≥300 incidence in NCFB and CF cohorts. METHODS: From January 2023 to October 2024, BEC were measured in 9,953 stable bronchiectasis patients across Mayo Clinic, including 9,806 with NCFB (J47.9; 66,780 CBCs) and 147 with CF (E84.0; 1,405 CBCs). Incidence of BEC≥300 was evaluated in relation to CBC frequency and timing (i.e., BEC≥300 on first, second, last, any, any two, first two simultaneously) and the number of CBCs per patient. RESULTS: In the NCFB cohort, median age was 74 years (IQR:66-82), with 59.5% female. Median CBCs/patient was 3 (IQR:1-7). Incidence of BEC≥300 on the first CBC was 19.8%. Among patients with ≥2 CBCs (n=7,075), incidence was 20.1% on the first, 19.8% on the second, and 20.0% on the last. This incidence rose to 36.3% when considering any CBC/patient. BEC≥300 on at least two CBCs was 29.3%, decreasing to 11.8% when considering consecutive BEC≥300 on both first and second CBCs. The incidence of BEC≥300 increased linearly with the number of CBCs obtained: 24.6% for those with 1-3 CBCs, up to 64.6% for >12 CBCs. In the CF cohort, median age was 36 years (IQR:27-52), with 55.1% female. Median CBCs/patient was 4 (IQR:2-8). BEC≥300 was present in 22.9% of first CBCs, rising to 36.3% when considering any CBC and 29.3% when present on at least two CBCs. Similar to the NCFB cohort, incidence increased with the number of CBCs: 26.5% for 1-3, up to 77.3% for >12. CONCLUSIONS: The incidence of BEC≥300 in our NCFB cohort remained steady at 20% at any specific measurement point, consistent with prospective literature. However, nearly half of those with BEC≥300 on the first or second CBC did not meet this threshold on both. Incidence significantly increased when any CBC was considered, and more CBCs were available. Similar observations were made in the CF cohort. Clearer BEC assessment strategies are needed to define clinically significant eosinophilic inflammation in bronchiectasis, to better identify patients who may most benefit from type 2 inflammation-targeted treatments.

Abstract Purpose: Frail and malnourished patients with bronchiectasis have worse outcomes. This study examines frailty and malnutrition as predictors of 30-day readmission after bronchiectasis exacerbation (BE). Methods: We utilized the 2018 Nationwide Readmissions Database to analyze hospitalizations for BE. Patients with BE were identified through principal and secondary ICD-10 diagnosis codes J47.0 and J47.1. Among those who survived the index hospitalization, only individuals discharged to home were included in the analysis. The primary objective was to identify predictors of 30-day readmission, with a specific focus on frailty and malnutrition. Frailty was measured using the validated Hospital Frailty Risk Score, as described by Gilbert et al. (Lancet, 2018), while malnutrition was identified using ICD-10 codes E43, E44.0, E44.1, and E46. Comorbidity burden was categorized using the Charlson Comorbidity Index: mild (score 0-2), moderate (3-5), and severe (≥6). A multivariate logistic regression model was employed to calculate adjusted odds ratios (ORs) for readmission, with statistical significance defined as p < 0.05. Results: Among 20,742 patients discharged home following bronchiectasis exacerbation, 4% (830) were readmitted within 30 days. Patients with readmission were younger (median age 63 vs. 69 years, p<0.01) and more likely to be treated at urban hospitals (84.9% vs. 80.0%, p=0.01). They also had higher rates of frailty (52.6% vs. 46.5%, p=0.01), malnutrition (21.0% vs. 14.7%, p<0.01), and Pseudomonas pneumonia (5.9% vs. 3.9%, p=0.03). The comorbidity burden was not different (p=0.29). After adjusting for age, malnutrition demonstrated a trend toward higher odds of readmission (OR 1.31, 95% CI 0.99-1.73, p=0.059), though this did not reach statistical significance. In contrast, frailty was significantly associated with increased readmission (OR 1.36, 95% CI 1.12-1.66). The presented Table describes the demographic characteristics and outcomes of ALL hospitalized patients with BE (n = 40, 789) stratified by frailty and malnutrition. Conclusions: Frailty is a significant predictor of 30-day readmission following BE. Targeted interventions addressing frailty in hospitalized patients with BE may help reduce readmission rates.

Abstract Rationale: Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by the accumulation of surfactant in the alveoli, primarily seen in autoimmune PAP (aPAP), which accounts for over 90% of cases. The COVID-19 pandemic has highlighted the potential for viral infections to exacerbate or induce PAP, complicating diagnosis and treatment. Objective: This study aims to provide updated clinical and demographic characteristics of patients with pulmonary alveolar proteinosis (PAP) and to analyze trends in the use of whole lung lavage before the COVID-19 pandemic, as well as assess the impact of the pandemic on WLL utilization. Methods: Using data from the National Inpatient Sample from 2017 to 2021, the authors identified PAP, other diagnoses, and procedures. using the respective ICD-10 codes. Statistical analysis was performed on the trends of whole lung lavage and other outcomes across the five years. Results: A total of 3,030 hospitalized PAP patients were included in the study, with demographic and clinical characteristics reported for the cohort. Although the use of WLL increased from 11.55% pre-pandemic to 14.67% during the pandemic, this difference was not statistically significant. However, there was a significant rise in the incidence of acute respiratory failure during the pandemic (35.7% vs. 45.78%, p = 0.02). While transbronchial lung biopsies increased and open lung biopsies declined, these trends were not statistically significant. Conclusion: In recent years, despite a decline in the use of WLL for treating PAP and open lung biopsies for diagnosis, the rates have risen due to the impact of the COVID-19 pandemic.