Winthrop, K.L.

Abstract Introduction Bronchiectasis is a chronic respiratory disease that increases fatigue, disability, and impairs quality of life. However, the impact of fatigue on patients with bronchiectasis, even in short-term follow-up, has not been sufficiently examined. We explored the association between fatigue and clinical outcomes among patients with bronchiectasis. Methods Adult bronchiectasis patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry were retrospectively analyzed. Patients with at least one annual follow-up visit in the 3-5 years post baseline and with fatigue data at both baseline and follow-up were included. Patients were grouped as experiencing fatigue versus not experiencing fatigue in the 2-years prior to baseline as reported at their baseline visit. We explored the relationship between baseline fatigue with patient demographics, co-existing conditions, components of the modified bronchiectasis severity index at baseline and follow-up. Wilcoxon, chi-square, and Fisher’s exact tests were used to assess the differences in continuous variables and associations between categorical variables, respectively. Stepwise multivariable logistic regression models explored the relationship of baseline fatigue with exacerbations and hospitalizations at follow-up. Model selection predictors were evaluated based on clinical relevance or p < 0.05 in univariable analyses. Results 1265 adults with bronchiectasis met the inclusion criteria. 563(45%) reported experiencing fatigue and 702 (55%) did not. The median age (interquartile range) was 70(62-78) years and patients were predominantly female (n = 1042, 83%). At baseline, patients experiencing fatigue had a higher proportion of co-existing diagnoses such as gastroesophageal reflux disease, chronic obstructive pulmonary disease, and rheumatologic disease, compared to those without fatigue (all p < 0.05). Furthermore, patients with fatigue had a higher prevalence of pulmonary-related hospitalizations (p < 0.001) at baseline and follow-up. Pseudomonas aeruginosa colonization and elevated dyspnea (modified Medical Research Council [mMRC] grade≥1) were more prevalent among those experiencing baseline fatigue compared to those without (all, p < 0.05). History of prior exacerbations (Odds Ratio [OR]:1.67, 95% CI:1.17-2.41) and baseline Pseudomonas aeruginosa colonization (OR:1.22, 95% CI:1.01-1.47) were significantly associated with increased odds of exacerbations at follow-up. In multivariable stepwise logistic regression, there was an increased odds of at least 1-hospitalization at follow-up among males (OR:2.23, 95% CI 1.12-4.42), patients with decreased Body Mass Index (OR:0.93, 95% CI: 0.87-1.0), and among patients with elevated dyspnea (mMRC grade ≥1) at baseline (OR:2.22, 95% CI: 1.16-4.24),[Table 1]. Conclusions Fatigue in bronchiectasis patients is associated with a more severe disease and greater healthcare utilization, although it may not independently predict future exacerbations or hospitalizations when accounting for other factors. This abstract is funded by: Bronchiectasis and NTM Association

Abstract Introduction Burkholderia, Achromobacter, and Stenotrophomonas species are associated with worse clinical outcomes in cystic fibrosis (CF),1 though little is known about their prevalence or pathogenicity in non-CF bronchiectasis (pwBE). Herein we describe the prevalence and clinical characteristics of pwBE who isolated each of these three organisms. Methods We conducted a retrospective cross-sectional analysis of baseline data from the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR). Adult bronchiectasis patients with known Achromobacter, Burkholderia cepacia complex (BCC), or Stenotrphomonas maltophilia culture results were included. Patients were stratified according to the presence of at least one positive culture among the gram-negative species. Demographics, clinical characteristics, and first annual follow-up culture results were summarized descriptively for the overall study population and between groups. No inferential analyses or hypothesis testing was performed. Results 5003 pwBE met the inclusion criteria, of which 39 (0.78%) isolated Achromobacter species, 11 isolated Burkholderia (0.22%), and 288 isolated Stenotrophomonas maltophilia (5.8%). Patients with Achromobacter were older, with a median age (interquartile range) of 76 (73.0-79.0) years, compared to the overall bronchiectasis cohort (69.0 years). Those with Burkholderia or Stenotrophomonas were younger, at 69.0 (53.0-75.0) and 71.0 (63.0-77.0) years, respectively. A high proportion of those with Achromobacter were male (31%) versus those with Burkholderia (9%) and Stenotrophomonas (24%), were current or former smokers (46%), were more likely to have had one or more exacerbations in the 2 years prior to enrollment (87%) than the overall BE cohort (57%), and were more likely to have had pulmonary-related hospitalization than those with either Burkholderia or Stenotrophomonas (46% vs. 27% and 19%, respectively). PwBE who isolated Burkholderia were less likely to have co-colonization with Pseudomonas aeruginosa or NTM species (9% each). At first annual follow-up, no patients with baseline Burkholderia isolated them at follow-up, and only 31% with baseline Stenotrophomonas isolated it at follow-up. Conclusion Overall prevalence of Achromobacter, Burkholderia, and Stenotrophomonas species in the BE cohort was low. Patients who isolated Achromobacter species were older, more likely to be current or former smokers, and more likely to experience pulmonary exacerbation and hospitalization. 15 patients who had not previously isolated Achromobacter, and 3 patients who had not previously isolated Burkholderia did so at annual follow-up. Interestingly, no patients with baseline Burkholderia isolates went on to isolate it at annual follow-up, which contradicts earlier studies in pwCF.2 The number of patients isolating Burkholderia in the U.S. BRR is very low, thereby limiting interpretation. This abstract is funded by: None

Abstract Introduction Persistent dyspnea increases the risk of disability and impairs quality of life in older patients with bronchiectasis. The impact of dyspnea and fatigue on patients with bronchiectasis in long term follow-up has not been adequately established. We sought to determine if fatigue and higher-grade dyspnea are associated with worse clinical outcomes in 5-years of longitudinal follow-up. Methods We analyzed data collected from a prospective cohort of adult patients with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry. Patients with a modified Medical Research Council (mMRC) dyspnea score collected at baseline and during 3-5 years of follow-up were included and stratified as mMRC<2 versus mMRC ≥2. Kruskal-Wallis, independent sample t-tests and chi-square tests were used to test the differences in medians and means for continuous variables and associations between categorical variables, respectively, between the baseline mMRC groups and bronchiectasis severity index (BSI) components at follow-up. A multivariable logistic regression analysis was performed to determine the association between dyspnea and clinical outcomes (exacerbations and hospitalizations) at follow-up. Results 1185 adult patients with bronchiectasis met the inclusion criteria. The median age (interquartile range) was 76 (68 to 83) years. At baseline, patients with mMRC ≥2 had a higher proportion of co-existing diagnoses such as asthma, chronic obstructive pulmonary disease (COPD), otitis/rhinosinusitis, rheumatologic disease, and pneumonia compared to patients with mMRC <2 (all p<0.05, data not shown). Furthermore, patients with mMRC > 2 compared to patients with mMRC <2 had higher prevalence of fatigue, acute exacerbations and pulmonary related hospitalizations, and lower mean percentage predicted forced expiratory volume in one second (FEV1) at follow-up (all p< 0.05) (Table 1). Interestingly, body mass index was slightly higher among those with baseline mMRC ≥2 compared to mMRC <2 (p=0.02). Among those with mMRC ≥2 at both baseline and follow-up (n=67, 42%), the odds of having ≥1 exacerbation was 2.4 times higher (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.45-4.1) and 2.8 times higher for ≥1 hospitalization (OR 2.8, 95% CI 1.45-5.2) during follow-up after adjusting for fatigue. Conclusion Elevated dyspnea was associated with a greater proportion of patients with bronchiectasis exhibiting acute exacerbations and pulmonary related hospitalizations and lower lung function during follow-up. Research is still needed to understand the causes (drivers) of dyspnea to implement better treatment strategies and reduce adverse outcomes in bronchiectasis patients.