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Towards development of evidence to inform recommendations for the evaluation and management of bronchiectasis

Flume, Patrick A; Basavaraj, Ashwin; Garcia, Bryan; Winthrop, Kevin; Di Mango, Emily; Daley, Charles L; Philley, Julie V; Henkle, Emily; O'Donnell, Anne E; Metersky, Mark
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.
PMID: 36931575
ISSN: 1532-3064
CID: 5462672

Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort

Maselli, Diego Jose; Yen, Andrew; Wang, Wei; Okajima, Yuka; Dolliver, Wojciech R; Mercugliano, Christina; Anzueto, Antonio; Restrepo, Marcos I; Aksamit, Timothy R; Basavaraj, Ashwin; Aliberti, Stefano; Young, Kendra A; Kinney, Gregory L; Wells, J Michael; San José Estépar, Raúl; Lynch, David A; Diaz, Alejandro A
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.
PMID: 34156303
ISSN: 1527-1315
CID: 4918322

A pre-post analysis assessing the 3-year long-term impact of high frequency chest wall oscillation therapy on clinical outcomes, healthcare cost and utilization in adult patients with non-cystic fibrosis bronchiectasis in the u.s [Meeting Abstract]

Basavaraj, A; Shah, D; DeKoven, M; Becker, B C; Urrea, C; Murray, A; Wanjala, M
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
ISSN: 1535-4970
CID: 4915722

Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study

Choate, Radmila; Aksamit, Timothy R; Mannino, David; Addrizzo-Harris, Doreen; Barker, Alan; Basavaraj, Ashwin; Daley, Charles L; Daniels, M Leigh Anne; Eden, Edward; DiMango, Angela; Fennelly, Kevin; Griffith, David E; Johnson, Margaret M; Knowles, Michael R; McShane, Pamela J; Metersky, Mark L; Noone, Peadar G; O'Donnell, Anne E; Olivier, Kenneth N; Salathe, Matthias A; Schmid, Andreas; Thomashow, Byron; Tino, Gregory; Winthrop, Kevin L; Stone, Glenda
RATIONALE/BACKGROUND:Non-cystic fibrosis bronchiectasis (NCFB) is characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Pseudomonas aeruginosa (PA) is one of the most frequently isolated pathogens in patients with NCFB. The purpose of this study was to evaluate the association between presence of PA and disease severity in patients within the US Bronchiectasis and Nontuberculous mycobacteria (NTM) Research Registry (BRR). METHODS:Baseline US BRR data from adult patients with NCFB collected between 2008 and 2018 was used for this study. The presence of PA was defined as one or more positive PA cultures within two years prior to enrollment. Modified Bronchiectasis Severity Index (m-BSI) and modified FACED (m-FACED) were computed to evaluate severity of bronchiectasis. Unadjusted and multivariable multinomial regression models were used to assess the association between presence of PA and severity of bronchiectasis. RESULTS: = 2.06 (95%CI:1.37-3.09) severity vs. low severity on m-BSI. CONCLUSION/CONCLUSIONS:The presence of PA is common in patients with NCFB within the Bronchiectasis and NTM Research Registry. Severity of bronchiectasis is significantly greater in patients with PA which emphasizes high burden of the disease.
PMID: 33401148
ISSN: 1532-3064
CID: 4738812

Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM Research Registry

Basavaraj, Ashwin; Choate, Radmila; Addrizzo-Harris, Doreen; Aksamit, Timothy R; Barker, Alan; Daley, Charles L; Anne Daniels, M Leigh; Eden, Edward; DiMango, Angela; Fennelly, Kevin; Griffith, David E; Johnson, Margaret M; Knowles, Michael R; Metersky, Mark L; Noone, Peadar G; O'Donnell, Anne E; Olivier, Kenneth N; Salathe, Matthias A; Schmid, Andreas; Thomashow, Byron; Tino, Gregory; Winthrop, Kevin L
BACKGROUND:In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies. RESEARCH QUESTION/OBJECTIVE:The primary objective was to describe differences in patients with bronchiectasis and productive cough who utilized ACTs and those who did not. Secondary objectives included assessment of bronchiectasis exacerbation frequency and change in pulmonary function at one-year follow-up. STUDY DESIGN/METHODS:and methods:Adult patients with bronchiectasis and productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow-up. Association between ACT use and clinical outcomes was assessed using unadjusted and adjusted multinomial logistic regression models. RESULTS:Of the overall study population (n=905), 59% utilized ACTs at baseline. A greater proportion of patients using ACTs at baseline and follow-up continuously had Pseudomonas aeruginosa (47% vs. 36%, p=0.021) and experienced an exacerbation (81% vs. 59%, p<0.0001) or hospitalization for pulmonary illness (32% vs. 22%, p=0.001) in the prior two years, compared to those not using ACTs. Fifty-eight percent of patients who utilized ACTs at baseline did not use ACTs at one-year follow-up. There was no significant change in pulmonary function for those that used ACTs at follow-up, compared to baseline. Patients using ACTs at baseline and follow-up had greater odds for experiencing exacerbations at follow-up compared to those not using ACTs.
PMID: 32622820
ISSN: 1931-3543
CID: 4517182

Nutrition and Markers of Disease Severity in Patients With Bronchiectasis

Despotes, Katherine A; Choate, Radmila; Addrizzo-Harris, Doreen; Aksamit, Timothy R; Barker, Alan; Basavaraj, Ashwin; Daley, Charles L; Eden, Edward; DiMango, Angela; Fennelly, Kevin; Philley, Julie; Johnson, Margaret M; McShane, Pamela J; Metersky, Mark L; O'Donnell, Anne E; Olivier, Kenneth N; Salathe, Matthias A; Schmid, Andreas; Thomashow, Byron; Tino, Gregory; Winthrop, Kevin L; Knowles, Michael R; Daniels, Mary Leigh Anne; Noone, Peadar G
Background/UNASSIGNED:Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S. Bronchiectasis Nontuberculous Mycobacterial Research Registry (U.S. BRR). Methods/UNASSIGNED:This was a retrospective, observational, longitudinal study using 5-year follow-up data from the BRR. Bronchiectasis was confirmed on computed tomography (CT). We stratified patients into nutrition categories using body mass index (BMI), and correlated BMI to markers of disease severity. Results/UNASSIGNED:, non-tuberculous mycobacteria, or by cause of bronchiectasis. The majority of patients demonstrated stable BMI over 5 years. Conclusions/UNASSIGNED:Although underweight patients with bronchiectasis have lower lung function, lower BMI does not appear to relate to other markers of disease severity in this patient population.
PMID: 33108111
ISSN: 2372-952x
CID: 4646522

Building the Pyramids [Editorial]

Bhatt, Alok; Nair, Sunil; Postelnicu, Radu; Basavaraj, Ashwin; Uppal, Amit; Mukherjee, Vikramjit
PMID: 32413345
ISSN: 1931-3543
CID: 4431752

Clinical Outcomes in Critically Ill Coronavirus Disease 2019 Patients: A Unique New York City Public Hospital Experience

Mukherjee, Vikramjit; Toth, Alexander T; Fenianos, Madelin; Martell, Sarah; Karpel, Hannah C; Postelnicu, Radu; Bhatt, Alok; Deshwal, Himanshu; Kreiger-Benson, Elana; Brill, Kenneth; Goldlust, Sandra; Nair, Sunil; Walsh, B Corbett; Ellenberg, David; Magda, Gabriela; Pradhan, Deepak; Uppal, Amit; Hena, Kerry; Chitkara, Nishay; Alviar, Carlos L; Basavaraj, Ashwin; Luoma, Kelsey; Link, Nathan; Bails, Douglas; Addrizzo-Harris, Doreen; Sterman, Daniel H
To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2.
PMID: 32885172
ISSN: 2639-8028
CID: 4583592

Evaluation of the airway microbiome in non-tuberculous mycobacteria

Sulaiman, Imran; Wu, Benjamin G; Li, Yonghua; Scott, Adrienne S; Malecha, Patrick; Scaglione, Benjamin; Wang, Jing; Basavaraj, Ashwin; Chung, Samuel; Bantis, Katrina; Carpenito, Joseph; Clemente, Jose C; Shen, Nan; Bessich, Jamie; Rafeq, Samaan; Michaud, Gaetene; Donington, Jessica; Naidoo, Charissa; Theron, Grant; Schattner, Gail; Garofano, Suzette; Condos, Rany; Kamelhar, David; Addrizzo-Harris, Doreen; Segal, Leopoldo N
Background: Aspiration is associated with non-tuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.Methods: 297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and a nested mycobacteriome sequencing approaches characterised microbiota composition. Inflammatory profiles of lower airway samples were also examined.Results: The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristic or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some non-pathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.Conclusions: The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples which are culture positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.
PMID: 30093571
ISSN: 1399-3003
CID: 3226712

The Microbiota of Non-Tuberculosis Mycobacterium Leads to a Distinct Inflammatory Profile [Meeting Abstract]

Sulaiman, I.; Wu, B.; Scaglione, B. D.; Wang, J.; Basavaraj, A.; Li, Y.; Scott, A. S.; Chung, S.; Bantis, K.; Clemente, J.; Shen, N.; Bessich, J. L.; Rafeq, S.; Michaud, G. C.; Donington, J. S.; Naidoo, C.; Theron, G.; Condos, R.; Kamelhar, D.; Addrizzo-Harris, D. J.; Segal, L. N.
ISSN: 1073-449x
CID: 3513172