Faculty Bibliography

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.

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.

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.

INTRODUCTION: Bronchiectasis is a common chronic pulmonary condition characterized by inflammation and recurrent infections. There is evidence that gastroesophageal reflux disease (GERD) is associated with bronchiectasis and can increase the severity of pulmonary disease. Data regarding esophageal function in this population is sparse. We aimed to assess whether patients with bronchiectasis have an increased prevalence of esophageal motility disturbances and GERD.
METHOD(S): We conducted a single-center matched cohort study of all adult patients with confirmed bronchiectasis who underwent esophageal high-resolution manometry (HRM) between 11/ 2014-3/2018. All cases were randomly matched with a control by age (65 years) and sex. Chicago Classification 3.0 was used to characterize HRM findings. Combined multichannel intraluminal impedance-pH (pH-MII) was utilized to assess reflux burden. Statistical relationships between proportions were evaluated by Chi-square or Fisher's exact test and continuous variables were compared using t-test or rank sum test.
RESULT(S): 63 bronchiectasis patients underwent HRM, of which 54 underwent pH-MII. Of the controls, 63 underwent HRM, of which 39 underwent pH-MII. Baseline characteristics between cases and controls were similar. Mean age of bronchiectasis patients was 65 (SD 12.73), mean body mass index was 25.51 (SD 8.50), 70% were female, and 48% had a smoking history (Table). HRM did not demonstrate any significant differences between cases and controls. pH-MII trended towards a greater reflux burden among controls. However, nearly half of cases had conclusive evidence of pathologic reflux by esophageal acid exposure on pH-MII. On endoscopy, no significant differences were noted.
CONCLUSION(S): Esophageal motility and acid exposure did not significantly differ among patients with bronchiectasis and controls, which may indicate that esophageal physiology in bronchiectasis is not unique. Nevertheless, more than half of the bronchiectasis group had evidence of abnormal esophageal motility and almost half of patients had conclusive evidence of pathologic reflux. Small differences are likely due to the high prevalence of GERD and associated motility disorders in the control group. Larger studies are warranted to further characterize esophageal physiology in these patients and the potential impact on pulmonary pathology. (Table Presented)

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2.

Introduction: Treatment options for refractory MAC-LD are limited. By month 6 in CONVERT, culture conversion rates in adults with refractory MAC-LD were 29.0% (65/224) with ALIS, a nebulized, liposome-encapsulated amikacin formulation, + guideline-based therapy (GBT) vs 8.9% (10/112; P<.0001) with GBT alone.
Aim(s): We report safety, culture conversion durability, and functional response (6-minute walk test; 6MWT) with extended (up to 16 mo) ALIS therapy.
Method(s): In CONVERT, patients were randomly assigned to receive ALIS 590mg QD + GBT or GBT alone. Patients with culture conversion (3 consecutive monthly MAC-negative sputum cultures) by month 6 continued treatment for 12 months after the time of culture conversion.
Result(s): In patients who converted by month 6 and continued treatment, 63% (41/65) of those on ALIS+GBT and 30% (3/10) on GBT alone remained culture negative after 12 months of subsequent treatment; 63% (41/65) vs 0% (0/10) remained culture-negative 3 months off all antibiotics. There was no difference between treatment arms in the change in 6MWT distance from baseline to month 8 (P=0.84). Extended ALIS exposure did not alter overall safety findings (Griffith, AJRCCM 2018) with ALIS+GBT and GBT alone; respectively, 84.7% (195/223) and 50.9% (57/112) had respiratory treatment-emergent adverse events (TEAEs); 20.2% (45/223) and 20.5% (23/112) had serious TEAEs.
Conclusion(s): Addition of ALIS to GBT in patients with refractory MAC-LD improved culture conversion, which was maintained during therapy and for 3 months posttreatment. No new safety signals emerged with extended treatment

Objective/UNASSIGNED:This study compares and contrasts the clinical features of non-cystic fibrosis bronchiectasis with 3 uncommon disorders known to be associated with bronchiectasis but with distinctly different underlying defined pathophysiologic derangements, namely severe alpha-1 antitrypsin deficiency (AATD), common variable immunodeficiency (CVI) and primary ciliary dyskinesia (PCD). Methods/UNASSIGNED:The Bronchiectasis Research Registry provides a central database for studying patients with non-cystic fibrosis bronchiectasis. This report consists of information from 13 U.S. sites pertaining to the 3 study diagnoses. Patients with AATD (SZ and ZZ phenotypes only), CVI (patients with IgG≤500), PCD (history of physician diagnosed Kartagener's syndrome or PCD), and patients with confirmed absence of the above 3 diagnoses (idiopathic control group) were included in the study. Descriptive statistics were computed for the main demographic and clinical characteristics of the sample stratified by group. Values between the groups were compared using Kruskal-Wallis test, and Chi-squared/ Fisher's exact tests respectively. The significance level was set at 0.05. Software SAS 9.4 was used to perform the statistical analyses. Results/UNASSIGNED:were the organisms most commonly isolated from sputum. Mycobacterial infection was most commonly reported in those with AATD. Conclusion/UNASSIGNED:. A greater percentage of those with AATD reported mycobacterial lung involvement.

Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite ≥6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS+GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT-alone, n=112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS+GBT and 10 of 112 (8.9%) with GBT alone (OR, 4.22; 95% CI [2.08, 8.57]; P<0.001). Patients in the ALIS+GBT arm vs GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% CI, [2.00, 7.60]). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS+GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02344004.