Nebulized hypertonic saline and positive expiratory pressure device use in patients with bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry.

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.

Association between bronchiectasis exacerbations and longitudinal changes in FEV1 in patients from the US bronchiectasis and NTM research registry.

BACKGROUND: This study aimed to evaluate the association between the number of non-cystic fibrosis bronchiectasis (bronchiectasis) exacerbations during baseline and follow-up (objective 1) and to identify longitudinal changes in FEV1 associated with exacerbation frequency (objective 2). METHODS: This was a retrospective cohort study of adult patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry September 2008 to March 2020. Objective 1 outcome was association between exacerbations during baseline (24 months) and 0-to-24 month and 24-to-48 month follow-up windows. Objective 2 outcomes were change in FEV1 and FEV1 % predicted over 24 months stratified by baseline exacerbation frequency. RESULTS: Objective 1 cohort (N = 520) baseline frequency of any exacerbations was 59.2%. Overall, 71.4% and 75.0% of patients with ≥1 baseline exacerbations had ≥1 exacerbations during the 0-to-24 and 24-to-48 month follow-ups. Having ≥1 exacerbation during baseline was significantly associated with ≥1 exacerbation during the 0-to-24 month (P = 0.0085) and 24-to-48 month follow-ups (P=<0.0001). Objective 2 cohort (N = 431) baseline FEV1 was significantly lower in patients who had more exacerbations; however, decline in FEV1 from baseline was not significantly different between patients with 0, 1, and ≥2 exacerbations. In patients with more baseline exacerbations, FEV1 % predicted was significantly lower at baseline (P < 0.0001) and at 12 (P = 0.0002) and 24 month follow-ups (P < 0.0001). CONCLUSIONS: Patients with frequent bronchiectasis exacerbations may be more likely than those with less frequent exacerbations to experience disease progression based on future exacerbation frequency and lower FEV1 at baseline, although FEV1 decline may not differ by baseline exacerbation frequency.

Five-Year Outcomes Among U.S. Bronchiectasis and Nontuberculous Mycobacterial Registry Patients.

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. OBJECTIVE: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. METHODS: Patients in the United States Bronchiectasis and Nontuberculous Mycobacteria 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 forced expiratory volume in 1 second % predicted, age, hospitalization within 2 years before baseline, body mass index, and gender (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 irrespective 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.

Severity of bronchiectasis predicts use of and adherence to high frequency chest wall oscillation therapy - Analysis from the United States Bronchiectasis and NTM research registry.

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: NA.

Diagnostic Criteria and the Decision to Treat Nontuberculous Mycobacterial Pulmonary Disease.

The diagnosis of nontuberculous mycobacterial (NTM) pulmonary disease is based on three criteria: patient's symptoms, radiographic findings, and microbiologic results. The microbiologic criterion is the most complicated because it requires more than one positive sputum acid-fast bacilli culture. Clinicians are challenged to apply the diagnostic criteria in the context of variable patient symptoms, NTM pathogenicity, and host susceptibility. The decision to treat NTM pulmonary disease entails assessment of the risks and benefits of therapy and the patient's wishes and ability to receive treatment.

Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study.

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

Artificial Intelligence-based CT Assessment of Bronchiectasis: The COPDGene Study.

Background CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans. Purpose To determine the extent of AARs using an artificial intelligence-based chest CT and assess the association of AARs with exacerbations over time. Materials and Methods In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of airway dilatation) in each participant on chest CT scans was determined. Pulmonary exacerbations were prospectively determined through biannual follow-up (from July 2009 to September 2021). Multivariable zero-inflated regression models were used to assess the association between the percentage of airways with AAR greater than 1 and the total number of pulmonary exacerbations over follow-up. Covariates included demographics, lung function, and conventional CT parameters. Results Among 4192 participants (median age, 59 years; IQR, 52-67 years; 1878 men [45%]), 1834 had chronic obstructive pulmonary disease (COPD). During a 10-year follow-up and in adjusted models, the percentage of airways with AARs greater than 1 (quartile 4 vs 1) was associated with a higher total number of exacerbations (risk ratio [RR], 1.08; 95% CI: 1.02, 1.15; P = .01). In participants meeting clinical and imaging criteria of bronchiectasis (ie, clinical manifestations with ≥3% of AARs >1) versus those who did not, the RR was 1.37 (95% CI: 1.31, 1.43; P < .001). Among participants with COPD, the corresponding RRs were 1.10 (95% CI: 1.02, 1.18; P = .02) and 1.32 (95% CI: 1.26, 1.39; P < .001), respectively. Conclusion In ever-smokers with chronic obstructive pulmonary disease, artificial intelligence-based CT measures of bronchiectasis were associated with more exacerbations over time. Clinical trial registration no. NCT00608764 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Schiebler and Seo in this issue.

Treatment of Nontuberculous Mycobacterial (NTM) Pulmonary Infection in the US Bronchiectasis and NTM Registry: Treatment Patterns, Adverse Events, and Adherence to American Thoracic Society/Infectious Disease Society of America Treatment Guidelines.

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy.

Impact of initiation of amikacin liposome inhalation suspension on hospitalizations and other healthcare resource utilization measures: a retrospective cohort study in real-world settings.

BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) is an infection that is increasing in frequency, associated with substantial disease burden, and often refractory to treatment. Amikacin liposome inhalation suspension (ALIS) is the first therapy approved for refractory MAC-LD. In the CONVERT study of adult patients with refractory MAC-LD, adding ALIS to a multidrug background regimen showed evidence of MAC infection elimination in sputum by month 6, which was maintained in most patients through the end of treatment (≤ 12 months post-conversion). This study assessed changes in healthcare resource utilization (HCRU) among patients initiating ALIS in real-world settings. METHODS: This retrospective cohort study of the All-Payer Claims Database (October 2018-April 2020) included patients aged ≥ 18 years with ≥ 1 pharmacy claim for ALIS and ≥ 12 months of continuous health plan enrollment pre- and post-ALIS initiation. Respiratory disease-related (and all-cause) HCRU (hospitalizations, length of stay [LOS], emergency department [ED] visits, and outpatient office visits) were compared 12 months pre- and post-ALIS initiation. Outcomes were reported at 6-month intervals; 0-6 months pre-ALIS initiation was the reference period for statistical comparisons. RESULTS: A total of 331 patients received ALIS, with HCRU highest in the 6 months pre-ALIS initiation. Compared with 26.9% during the reference period, respiratory-related hospitalizations decreased to 19.3% (P < 0.01) and 15.4% (P < 0.0001) during 0-6 and 7-12 months post-ALIS initiation, respectively. Mean number of respiratory disease-related hospitalizations per patient/6-month period decreased from 1.0 (reference period) to 0.6 (P < 0.0005) at both timepoints post-ALIS initiation. A similar pattern was observed for all-cause hospitalizations and hospitalizations per patient/6-month period (both P < 0.005). Reductions in all-cause and respiratory disease-related LOS post-ALIS initiation were significant (both P < 0.05). ED visits were few and unchanged during the study. Significant reductions per patient/6-month period in all-cause and respiratory-related outpatient office visits were observed post-ALIS initiation (all P < 0.01). CONCLUSIONS: In this first real-world study of ALIS, respiratory disease-related (and all-cause) hospitalizations and outpatient visits were reduced in the 12 months following ALIS initiation. The results of this study provide HCRU-related information to better understand the impact of initiating ALIS treatment. TRIAL REGISTRATION: Not appliable.

Artificial Intelligence-Augmented Propensity Score, Cost Effectiveness and Computational Ethical Analysis of Cardiac Arrest and Active Cancer with Novel Mortality Predictive Score.

Background and objectives: Little is known about outcome improvements and disparities in cardiac arrest and active cancer. We performed the first known AI and propensity score (PS)-augmented clinical, cost-effectiveness, and computational ethical analysis of cardio-oncology cardiac arrests including left heart catheterization (LHC)-related mortality reduction and related disparities. Materials and methods: A nationally representative cohort analysis was performed for mortality and cost by active cancer using the largest United States all-payer inpatient dataset, the National Inpatient Sample, from 2016 to 2018, using deep learning and machine learning augmented propensity score-adjusted (ML-PS) multivariable regression which informed cost-effectiveness and ethical analyses. The Cardiac Arrest Cardio-Oncology Score (CACOS) was then created for the above population and validated. The results informed the computational ethical analysis to determine ethical and related policy recommendations. Results: Of the 101,521,656 hospitalizations, 6,656,883 (6.56%) suffered cardiac arrest of whom 61,300 (0.92%) had active cancer. Patients with versus without active cancer were significantly less likely to receive an inpatient LHC (7.42% versus 20.79%, p < 0.001). In ML-PS regression in active cancer, post-arrest LHC significantly reduced mortality (OR 0.18, 95%CI 0.14−0.24, p < 0.001) which PS matching confirmed by up to 42.87% (95%CI 35.56−50.18, p < 0.001). The CACOS model included the predictors of no inpatient LHC, PEA initial rhythm, metastatic malignancy, and high-risk malignancy (leukemia, pancreas, liver, biliary, and lung). Cost-benefit analysis indicated 292 racial minorities and $2.16 billion could be saved annually by reducing racial disparities in LHC. Ethical analysis indicated the convergent consensus across diverse belief systems that such disparities should be eliminated to optimize just and equitable outcomes. Conclusions: This AI-guided empirical and ethical analysis provides a novel demonstration of LHC mortality reductions in cardio-oncology cardiac arrest and related disparities, along with an innovative predictive model that can be integrated within the digital ecosystem of modern healthcare systems to improve equitable clinical and public health outcomes.

Comparative safety of inhaled corticosteroids and macrolides in Medicare enrolees with bronchiectasis.

Introduction: Bronchiectasis is an increasingly common chronic inflammatory airway disease. We evaluated secondary safety outcomes in a comparative effectiveness study of chronic inhaled corticosteroids (ICS) and macrolide monotherapy in bronchiectasis patients. Methods: We conducted a retrospective study using US Medicare Parts A, B and D (but not C) 2006-2014 datasets. Among those with a pulmonologist-associated bronchiectasis claim (ICD-9-CM 494.0 or 494.1), without cystic fibrosis, we identified the first new use of either chronic (>28 days) ICS or macrolide monotherapy. For each drug exposure, we calculated crude incidence rates of the secondary safety outcomes: arrhythmia, myocardial infarction, sensorineural hearing loss, hip fracture and opportunistic infections. We calculated a propensity score (PS) for ICS use using demographic, clinical and utilisation characteristics and compared risks of macrolides versus ICS for each outcome using PS decile-adjusted Cox regression models. Results: Of 285 043 Medicare patients with bronchiectasis, we identified 6500 (2%) macrolide and 83 589 (29%) ICS new users. Key covariates were balanced across exposure groups within decile. Myocardial infarction, hip fracture and opportunistic infection were not significantly associated with treatment. Macrolides were associated with a decreased risk of arrhythmia (adjusted hazard ratio (aHR) 0.87, 95% CI 0.80-0.94) and an increased risk of sensorineural hearing loss (aHR 1.38, 95% CI 1.56-1.22) compared to ICS. Conclusions: Macrolides were not associated with an elevated risk of acute cardiac events compared to ICS. The increased risk of hearing loss in macrolide users compared to ICS users in older bronchiectasis patients should be balanced against known benefits of macrolides.

Stenotrophomonas maltophilia in patients with bronchiectasis: An analysis of the US bronchiectasis and NTM Research Registry.

INTRODUCTION: Little information is available about Stenotrophomonas maltophilia in patients with bronchiectasis. We analyzed data from the US Bronchiectasis and NTM Research Registry to determine its prevalence and association with patient characteristics and severity of disease. METHODS: Baseline and follow-up data were entered into a central web-based database. Patients were grouped into four cohorts based on their baseline cultures: 1) S. maltophilia, no Pseudomonas aeruginsosa, 2) P. aeruginosa, no S. maltophilia, 3) No pathogens, 4) Pathogens other than P. aeruginosa and S. maltophilia. The association between S. maltophilia, demographic characteristics, pulmonary function, exacerbations and hospitalizations was assessed at baseline and one year follow-up. RESULTS: Among 2659 patients, 134 (5.0%) had grown S. maltophilia at baseline. The prior exacerbation rate at baseline was similar in patients with S. maltophilia and P. aeruginosa, but significantly higher than the other two groups. Hospitalizations were more frequent in patients with S. maltophilia or P. aeruginosa. Pre-bronchodilator FEV1 among S. maltophilia patients was between that of Pseudomonas patients and patients without either organism, but was not significantly different from any of the other groups. For all risk-adjusted one-year outcomes, patients with S. maltophilia had a non-significant trend towards worse outcomes compared to patients without P. aeruginosa, but were more similar to patients with P aeruginosa. DISCUSSION: Bronchiectasis patients with S. maltophilia may have worse outcomes than patients without this organism or without P. aeruginosa; further study is needed to determine if the non-significant trends we note are clinically significant.

New therapies for nontuberculous mycobacterial lung infection.

PURPOSE OF REVIEW: Although nontuberculous mycobacterial pulmonary disease is increasing in incidence, outcomes remain less than optimal highlighting the unmet need for developing novel therapies. RECENT FINDINGS: Several new antibiotic formulations, novel antibiotics, and novel nonantibiotic treatments have recently demonstrated positive results in treating nontuberculous mycobacterial pulmonary disease. SUMMARY: Promising novel therapies are currently under investigation fueling much needed interest and enthusiasm in the nontuberculous mycobacterial pulmonary disease space and will hopefully lead to improved understanding and outcomes in this complex disease.

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.