Faculty Bibliography

BACKGROUND AND OBJECTIVE/UNASSIGNED:Treatable traits in bronchiectasis have been classified as pulmonary, etiological, extra-pulmonary and behavioral or lifestyle factors. A range of non-pharmacological interventions may be applied to address these traits, with selected therapies applicable to multiple traits. The aim of this narrative review was to synthesize the evidence for non-pharmacological therapies through the lens of treatable traits for adults with bronchiectasis and highlight the clinical effects of these treatments. METHODS/UNASSIGNED:Electronic searches of PubMed and Medline using specific keywords were conducted. Articles underwent screening for relevance, with potential sources from review articles, systematic and scoping reviews, case series, prospective and retrospective studies, clinical practice guidelines and statements, and editorials in peer-reviewed journals. The data included were limited to English publications from 1980 to 2024. KEY CONTENT AND FINDINGS/UNASSIGNED:Of those traits which fall under the pulmonary and etiology categories, treatment options include airway clearance therapy, adjuncts to airway clearance such as mucoactive agents, smoking cessation programs, non-invasive ventilation and oxygen therapy, including high flow nasal therapy. Extra-pulmonary traits that are amenable to non-pharmacological approaches included psychological symptoms, nutritional concerns, gastroesophageal reflux disease, rhinosinusitis and cardiovascular disease. Treatment options span from cognitive behavioral therapy and counselling, nutritional advice and supplements, lifestyle adjustments and nasal-sinus irrigation. Key behavioral or lifestyle traits are low treatment adherence, smoking and lack of exercise. These are addressed via education and self-management programs, smoking cessation, pulmonary rehabilitation and other forms of exercise or physical activity. CONCLUSIONS/UNASSIGNED:A variety of non-pharmacological therapies may be applied to address treatable traits in those with bronchiectasis and adopting an integrated approach is important to optimize patient outcomes. Further studies could guide the implementation of non-pharmacological interventions for newly identified treatable traits in this population.

BACKGROUND:Nebulized Hypertonic saline (HS) and positive expiratory pressure device (PEP) are often used in patients with bronchiectasis. We sought to describe the clinical characteristics in patients using HS and PEP, utilizing a large national database registry. METHODS:Data from the US Bronchiectasis and NTM Research Registry were used in this study. Patients with a diagnosis of bronchiectasis were included. Eligible patients were assigned to one of four mutually exclusive groups: HS only, PEP only, HS & PEP, or no airway clearance or mucoactive agent. Descriptive statistics were computed for the overall study population and stratified by the four groups. One-way ANOVA and chi-square tests were used to test the difference in the means in continuous variables and the association between categorical variables (respectively) across the four groups. RESULTS:A total of 2195 patients were included. Of those with bronchiectasis and a productive cough, a greater number of patients utilized HS only vs PEP only (17.5 % vs 9.1 %, p < 0.001). Similar association was found in those with Pseudomonas aeruginosa (22.3 % HS only vs 6.5 % PEP only, p < 0.001). There was a higher number of patients who used HS and PEP therapy in combination vs PEP therapy alone (25.0 % vs 9.1 %, p = 0.002), in those with a productive cough. CONCLUSIONS:In patients with bronchiectasis and a productive cough or Pseudomonas aeruginosa, HS is used more often than PEP alone. There is a need for further analysis to compare these two modalities and explore the factors influencing their utilization.

BACKGROUND:High frequency chest wall oscillation (HFCWO) is a form of airway clearance therapy that has been available since the mid-1990s and is routinely used by patients suffering from retained pulmonary secretions. Patients with cystic fibrosis (CF), neuromuscular disease (NMD), and other disorders, including bronchiectasis (BE) and COPD (without BE), are commonly prescribed this therapy. Limited evidence exists describing HFCWO use in the BE population, its impact on long-term management of disease, and the specific patient populations most likely to benefit from this therapy. This study sought to characterize the clinical characteristics of patients with BE who have documented use of HFCWO at baseline and 1-year follow-up. METHODS:An analysis from a large national database registry of patients with BE was performed. Demographic and clinical characteristics of all patients receiving HFCWO therapy at baseline are reported. Patients were stratified into two groups based on continued or discontinued use of HFCWO therapy at 1-year follow-up. RESULTS:Over half (54.8 %) of patients who reported using HFCWO therapy had a Modified Bronchiectasis Severity Index (m-BSI) classified as severe, and the majority (81.4 %) experienced an exacerbation in the prior two years. Of patients with 1-year follow-up data, 73 % reported continued use of HFCWO. Compared to patients who discontinued therapy, these patients were more severe at baseline and at follow-up suggesting that patients with more severe disease are more likely to continue HFCWO therapy. CONCLUSIONS:Patients who have more severe disease and continue to experience exacerbations and hospitalizations are more likely to continue HFCWO therapy. CLINICAL TRIAL REGISTRATION/BACKGROUND:NA.

Bronchiectasis (BE) is a chronic condition characterized by airway dilation as a consequence of a variety of pathogenic processes. It is often associated with persistent airway infection and an inflammatory response resulting in cough productive of purulent sputum, which has an adverse impact on quality of life. The prevalence of BE is increasing worldwide. Treatment guidelines exist for managing BE, but they are generally informed by a paucity of high-quality evidence. This review presents the findings of a scientific advisory board of experts held in the United States in November 2020. The main focus of the meeting was to identify unmet needs in BE and propose ways to identify research priorities for the management of BE, with a view to developing evidence-based treatment recommendations. Key issues identified include diagnosis, patient evaluation, promoting airway clearance and appropriate use of antimicrobials. Unmet needs include effective pharmacological agents to promote airway clearance and reduce inflammation, control of chronic infection, clinical endpoints to be used in the design of BE clinical trials, and more accurate classification of patients using phenotypes and endotypes to better guide treatment decisions and improve outcomes.

Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV₁, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.

RATIONALE High Frequency Chest Wall Oscillation (HFCWO) is an airway clearance therapy prescribed for patients with non-cystic fibrosis bronchiectasis. The objective of this study was to examine the long-term impact of HFCWO among bronchiectasis patients in the United States. METHODS A retrospective pre-post cohort study was conducted using the IQVIA PharMetrics Database. The population of interest was patients with bronchiectasis receiving HFCWO (1st claim=Index date) between January 1, 2009 and November 30, 2018. Clinical outcomes, healthcare resource utilization (HCRU) and costs were measured in the 12-month pre- and 36 month post-index periods. Comparisons were conducted using McNemar's test for categorical variables and the Wilcoxon signed-rank test for continuous variables. RESULTS One hundred thirty-nine subjects and 73 met two year and three year criteria, respectively. The mean age of the cohort was 55.8 years (SD=14.5), and predominantly female (69.9%). Fifty-four percent had a high risk Bronchiectasis Aetiology and Comorbidity Index (BACI) score. In all-cause outcomes, the proportion of oral antibiotic use reduced by 8% in year one (P=0.03), 13% in year two (P<0.01) and 16% in year three (P=0.01) after initiation of HFCWO, compared to baseline. Inhaled beta agonist/steroid use reduced in all three years (P<0.03). IV antibiotic use trended down. Emergency room visits reduced by 33% in year two (P<0.01). Pulmonologists visits reduced in all three years (P<0.01). Chest X-ray use reduced by 28% in year two (P<.001) and 38% in year three (P<.001). Bronchoscopy use reduced significantly as well (P<0.01) in all three years. The median all-cause hospital length of stay reduced by 25% in year three (P=0.02). In disease-specific outcomes, the proportion of physician office visits reduced in all three years, compared to baseline (P<.001). Bronchoscopy, laboratory, and radiology utilization significantly reduced in all three years. Ancillary services use increased in year one by 21% (P<.001), however reduced by 19% in year two (P<0.01) and 46% in year three (P<.001). Hospitalizations and exacerbations both reduced by 73% in year one (P=0.03) and 64% in year two (P=0.03). Mean total disease-specific costs increased by $8,029 in year one (P<.001), likely due to device costs. At year two, total costs reduced by $2,065 (P<0.01), and reduced further at year three by $3,459 (P<0.01). Mean disease specific hospitalization costs reduced by 80% within the first year (P=0.03). CONCLUSIONS High frequency chest wall oscillation therapy may provide significant long-term clinical benefits and cost savings to patients with bronchiectasis. Further study is needed