Brunton, Amanda E.

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 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.

Abstract Introduction: Non-Cystic Fibrosis Bronchiectasis (NCFB) is an obstructive pulmonary disease associated with structural lung disease, altered mucociliary clearance, hyper mucus secretion, recurrent infection, and airway inflammation that results in significant morbidity and mortality. Aspergillus sp (Asp) is a common fungi isolated in respiratory specimens of those with lung disease and is associated with both infectious and allergic pulmonary diseases such as Asthma and Cystic Fibrosis. Despite individuals with NCFB having similar phenotypes as these conditions, the impact of Asp on this population is poorly understood. Methods: We performed a cross-sectional retrospective analysis from the US Bronchiectasis and NTM Research Registry (BRR). NCFB patients without a history of lung transplant who had at least one respiratory Asp culture were included. We compared patients with no history of Asp grown from respiratory culture to those with at least one positive respiratory culture for Asp during the available period. Patient demographics, bacterial culture history, lung function, comorbidities, modified Bronchiectasis Severity Index (mBSI), and sputum parameters were analyzed descriptively. Comparisons between groups were conducted using Kruskal-Wallis, independent sample t-tests, and chi-square tests for continuous and categorical variables as appropriate. Results: 3985 people with NCFB met inclusion criteria. 3359 (84.3%) individuals were Asp culture negative compared to 626 (15.7%) individuals with Asp. There were notable differences in race, showing higher proportions of non-Hispanic white (90.4 vs 82.2%) in this population. While the frequency of Chronic Obstructive Pulmonary Disease and Primary Ciliary Dyskinesia were similar, there were more individuals with Asthma (31.3 vs 24.7%, p<0.001) and Allergic Bronchopulmonary Aspergillosis (ABPA) (6.4 vs 2.4%, p<0.001) in the Asp positive group (Figure 1A). The Asp positive group had higher blood eosinophils (150.0 vs 124.0 cells/uL, p=0.026, Figure 1B), had nominally lower lung function (73.5 vs 75.3% ppFEV1, p=0.089), and were more likely to have at least one or more positive bacterial cultures (62.9 vs 51.9%, p<0.001, Figure 1C). There was no significant difference in sex, age, exacerbations, Pseudomonas aeruginosa or NTM positive cultures, sputum volume, or mBSI. Conclusion: Individuals with NCFB and history of one or more positive Asp cultures were more likely to be non-Hispanic white, have a diagnosis of Asthma and/or ABPA, higher blood eosinophils, and more positive airway bacterial cultures. Further work is needed to better understand how Asp contributes to bronchiectasis progression. More expansive analysis and multivariant modeling is underway to better understand the impact of Asp in people with NCFB.

Abstract Rationale Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Abstract Background Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic lung infection that is challenging to treat, especially refractory NTMPD. Data are limited on the natural history, risk profile, and burden of refractory NTMPD. The objective of this study was to evaluate the burden of illness (BOI) among patients with NTMPD who later develop refractory NTMPD vs those who do not. Methods This was a retrospective analysis using BRR data. Patients treated for NTMPD were included and stratified as refractory (received oral clofazimine/bedaquiline or inhaled amikacin/ALIS, or remained sputum culture positive despite ≥ 6 months of treatment) or nonrefractory. Modified bronchiectasis severity index (mBSI) at baseline visit and BOI including comorbid conditions and surgeries at the treatment visit were compared by cross-sectional analysis between the two groups. Longitudinal analysis of BOI focused on exacerbations and hospitalizations in the refractory group at their pre-refractory visit and refractory visit (first visit meeting the refractory definition). Results A total of 1,064 patients treated for NTMPD were included: 462 (43.4%) refractory and 602 (56.6%) nonrefractory. During the baseline period, the refractory group had more severe bronchiectasis (Table 1, mBSI, mean [SD], 7.3 [3.4] vs 6.7 [3.4]). At the time of treatment, bronchiectasis was more common in the refractory than nonrefractory (96.2% vs 89.7%) group, as were hemoptysis (26.6% vs 16.3%) and GERD (50.5% vs 39.9%). Except BMI, there were no statistically significant differences between the pre-refractory and nonrefractory treatment visits (Table 2). In the refractory group, exacerbations and hospitalizations remained high from the pre-refractory to refractory visit (45.6% vs 39.4% and 13.3% vs 12.8%, respectively). Oxygen and bronchial hygiene use increased from the pre-refractory to the refractory visit (5.2% vs 9.3% and 54.5% vs 61.7%, respectively) consistent with increased management of respiratory conditions when not responding to treatment (Table 2). Conclusion Refractory NTMPD imposes a high disease burden on patients in the BRR. This high burden was present at pre-refractory visits and through the development of refractory status. Disclosures Timothy R. Aksamit, MD, AstraZeneca: Advisor/Consultant|Baxter International, Hill-Rom: Advisor/Consultant|Insmed Incorporated: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Redhill Biopharma: Advisor/Consultant|RespirTech: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Zambon: Advisor/Consultant David M. Mannino, MD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Up to Date: Advisor/Consultant Ping Wang, PhD, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds Mariam Hassan, PhD, B. Pharm, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds