The role of chest computed tomography in the evaluation and management of chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: The purpose of this review is to compile recent data on the clinical associations of computed tomography (CT) scan findings in the literature and potential avenues for implementation into clinical practice. RECENT FINDINGS: Airways dysanapsis, emphysema, chronic bronchitis, and pulmonary vascular metrics have all recently been associated with poor chronic obstructive pulmonary disease (COPD) outcomes when controlled for clinically relevant covariables, including risk of mortality in the case of emphysema and chronic bronchitis. Other authors suggest that CT scan may provide insight into both lung parenchymal damage and other clinically important comorbidities in COPD. SUMMARY: CT scan findings in COPD relate to clinical outcomes. There is a continued need to develop processes to best implement the results of these studies into clinical practice.

Predicting Adverse Events Among Patients With COPD Exacerbations in the Emergency Department.

BACKGROUND: COPD exacerbations lead to excessive health care utilization, morbidity, and mortality. The Ottawa COPD Risk Scale (OCRS) was developed to predict short-term serious adverse events (SAEs) among patients in the emergency department (ED) with COPD exacerbations. We assessed the utility of the OCRS, its component elements, and other clinical variables for ED disposition decisions in a United States population. METHODS: We compared the OCRS and other factors in predicting SAEs among a retrospective cohort of ED patients with COPD exacerbations. We followed subjects for 30 d, and the primary outcome, SAE, was defined as any death, admission to monitored unit, intubation, noninvasive ventilation, major procedure, myocardial infarction, or revisit with hospital admission. RESULTS: A total of 246 subjects (median 61-y old, 46% male, total admission rate to ward 52%) were included, with 46 (18.7%) experiencing SAEs. Median OCRS scores did not differ significantly between those with and without an SAE (difference: 0 [interquartile range 0-1)]. The OCRS predicted SAEs poorly (Hosmer-Lemeshow goodness of fit [H-L GOF] P ≤ .001, area under the receiver operating characteristic [ROC] curve 0.519). Three variables were significantly related to SAEs in our final model (H-L GOF P = .14, area under the ROC curve 0.808): Charlson comorbidity index (odds ratio [OR] 1.3 [1.1-1.5] per 1-point increase); triage venous PCO2 (OR 1.7 [1.2-2.4] per 10 mm Hg increase); and hospitalization within previous year (OR 9.1 [3.3-24.8]). CONCLUSIONS: The OCRS did not reliably predict SAEs in our population. We found 3 risk factors that were significantly associated with 30-d SAE in our United States ED population: triage [Formula: see text] level, Charlson comorbidity index, and hospitalization within the previous year. Further studies are needed to develop generalizable decision tools to improve safety and resource utilization for this patient population.

Oral Positive Expiratory Pressure Device for Excessive Dynamic Airway Collapse Caused by Emphysema.

Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George's Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema.

Cytomegalovirus Seropositivity is Associated with Airflow Limitation in a Cohort of Veterans with a High Prevalence of Smoking.

BACKGROUND: Cytomegalovirus (CMV) represents an understudied chronic infection, usually contracted early in life, that causes chronic immune system alterations which may contribute to airflow limitations in a cohort of veterans with a high prevalence of smoking. We studied 172 participants at-risk for and with airflow limitation with available CMV serology to assess the relationship between CMV infection and chronic obstructive pulmonary disease (COPD)-related outcomes. METHODS: The study cohort includes 172 veterans who are smokers with or at risk for the development of COPD. Clinical data were obtained by chart abstraction at enrollment. CMV affinity (ever-exposure) and avidity testing (length of exposure) were performed on plasma samples collected at enrollment. Bivariable and multivariable logistic regression was used to determine the relationship between both cytomegalovirus affinity and avidity and odds of prevalent airflow limitation (post-bronchodilator forced expiratory volume in 1 second to forced vital capacity ratio <0.70) at enrollment. In those with airflow limitation (n=84), bivariable and multivariable logistic regression was used to determine relationships between CMV serostatus and reported exacerbations of COPD over 2 years prior to enrollment. RESULTS: Positive CMV serostatus was independently associated with a 136% higher odds of airflow limitation (95% confidence interval 1.11-5.06, P=0.03) at enrollment. Neither CMV affinity nor avidity was associated with COPD exacerbations in the 2 years prior to enrollment. CONCLUSIONS: CMV serostatus is independently associated with airflow limitation in a cohort of veterans who smoke. Investigation into the timing of infection and alterations in cellular immunity caused by chronic CMV infection and smoking-related airways disease-related outcomes is warranted.

The STS case study: an analysis method for longitudinal qualitative research for implementation science.

BACKGROUND: Ethnographic approaches offer a method and a way of thinking about implementation. This manuscript applies a specific case study method to describe the impact of the longitudinal interplay between implementation stakeholders. Growing out of science and technology studies (STS) and drawing on the latent archaeological sensibilities implied by ethnographic methods, the STS case-study is a tool for implementors to use when a piece of material culture is an essential component of an innovation. METHODS: We conducted an ethnographic process evaluation of the clinical implementation of tele-critical care (Tele-CC) services in the Department of Veterans Affairs. We collected fieldnotes and conducted participant observation at virtual and in-person education and planning events (n = 101 h). At Go-Live and 6-months post-implementation, we conducted site visits to the Tele-CC hub and 3 partnered ICUs. We led semi-structured interviews with ICU staff at Go-Live (43 interviews with 65 participants) and with ICU and Tele-CC staff 6-months post-implementation (44 interviews with 67 participants). We used verification strategies, including methodological coherence, appropriate sampling, collecting and analyzing data concurrently, and thinking theoretically, to ensure the reliability and validity of our data collection and analysis process. RESULTS: The STS case-study helped us realize that we must think differently about how a Tele-CC clinician could be noticed moving from communal to intimate space. To understand how perceptions of surveillance impacted staff acceptance, we mapped the materials through which surveillance came to matter in the stories staff told about cameras, buttons, chimes, motors, curtains, and doorbells. CONCLUSIONS: STS case-studies contribute to the literature on longitudinal qualitive research (LQR) in implementation science, including pen portraits and periodic reflections. Anchored by the material, the heterogeneity of an STS case-study generates questions and encourages exploring differences. Begun early enough, the STS case-study method, like periodic reflections, can serve to iteratively inform data collection for researchers and implementors. The next step is to determine systematically how material culture can reveal implementation barriers and direct attention to potential solutions that address tacit, deeply rooted challenges to innovations in practice and technology.

How might endotyping guide chronic obstructive pulmonary disease treatment? Current understanding, knowledge gaps and future research needs.

PURPOSE OF REVIEW: This review discusses emerging therapies directed at chronic obstructive pulmonary disease (COPD) endotypes and pathobiological processes that manifest as the disease. RECENT FINDINGS: Specific endotypes have been targeted in COPD. These include eosinophilic inflammation, overproduction of interleukin-17, chronic bronchitis and altered nature of mucous, and chronic infection. Therapies exactly directed at the cause of these endotypes or their resultant clinical findings have been assessed. Although some intermediate outcomes have seemed promising, there have been no findings that shift the paradigm of COPD therapy. SUMMARY: Basic and clinical scientists continue to define endotypes that may be directly addressed with therapeutics. As of the time of this up-to-date review, there is yet to be an endotype-directed therapy to demonstrate great clinical effect.

Ultra Long-Acting ß-Agonists in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Inhaled ß-agonists have been foundational medications for maintenance COPD management for decades. Through activation of cyclic adenosine monophosphate pathways, these agents relax airway smooth muscle and improve expiratory airflow by relieving bronchospasm and alleviating air trapping and dynamic hyperinflation improving breathlessness, exertional capabilities, and quality of life. ß-agonist drug development has discovered drugs with increasing longer durations of action: short acting (SABA) (4-6 h), long acting (LABA) (6-12 h), and ultra-long acting (ULABA) (24 h). Three ULABAs, indacaterol, olodaterol, and vilanterol, are approved for clinical treatment of COPD. PURPOSE: This article reviews both clinically approved ULABAs and ULABAs in development. CONCLUSION: Indacaterol and olodaterol were originally approved for clinical use as monotherapies for COPD. Vilanterol is the first ULABA to be approved only in combination with other respiratory medications. Although there are many other ULABA's in various stages of development, most clinical testing of these novel agents is suspended or proceeding slowly. The three approved ULABAs are being combined with antimuscarinic agents and corticosteroids as dual and triple agent treatments that are being tested for clinical use and efficacy. Increasingly, these clinical trials are using specific COPD clinical characteristics to define study populations and to begin to develop therapies that are trait-specific.

Resting Borg score as a predictor of safe discharge of chronic obstructive pulmonary disease from the emergency department observation unit.

BACKGROUND: Chronic obstructive pulmonary disease exacerbations (eCOPD) can be life-threatening and costly. Emergency department (ED) observation units (ED-Obs) offer short-term care to safely reduce preventable hospitalizations. Accurately identifying eCOPD patients who can be discharged safely will improve outcomes. OBJECTIVES: The objective were to: I) evaluate utility of conventional clinical variables as predictors of safe discharge and II) assess utility of serial resting Borg score and novel Dyspnea Assessment Score (DAS) for identifying eCOPD patients who can be safely discharged from ED-Obs. METHODS: This study was carried out in a 680-bed tertiary, academic hospital with >700 annual eCOPD ED encounters and a 16-bed ED-Obs. A two-phase study of eCOPD patients admitted to ED-Obs was performed. Objective I was a retrospective study including all eCOPD admits from April 2016 to May 2017. Predictor variables (demographics, COPD severity, comorbid conditions, exacerbation severity, clinical care in ED) and outcome variables (ED-Obs disposition, ED revisits) were obtained through electronic medical records. Safe discharge was defined as home disposition from ED-Obs without 7-day revisit. A stepwise regression was performed for predictors of safe discharge. Objective II was a prospective observation study for change in every 4-hour serial resting Borg score and DAS as identifiers of safe discharge. Comparative and receiver operating characteristic (ROC) analyses were performed. A p-value of <0.05 was considered significant. RESULTS: In Objective I, 171 patients with age, FEV1 %, and body mass index of 59.8 (±9.5) years, 35 (±24)%, and 28.8 (±8) m2 /kg were included. After ED-Obs treatment 78 (45.6%) were hospitalized and 93 (54.4%) were discharged home, of whom 11 (6.4%) had 7-day ED revisit. Safe discharge occurred in 82 (48%). None of the predictor variables correlated with safe discharge. In Objective II, of 38 patients included, 20 (52.6%) had safe discharge. Among others, 16 (42%) were hospitalized and two (5.2%) had 7-day ED revisit. The admission Borg scores and DASs were similar in both groups. The predisposition Borg score was significantly lower in patients with safe discharge (2.75 vs. 5.28, p < 0.001) and had the highest area under curve on ROC (0.77) for safe discharge. DAS was not significantly different between groups. CONCLUSIONS: Routine clinical variables do not identify eCOPD patients who can be safely discharged from ED-Obs. Change in resting Borg score during the course of ED-Obs treatment safely identifies patients for discharge. Prospective, external validation is needed to incorporate serial Borg scores in ED-Obs disposition decision for improved safety.

Evaluation of clinician interaction with alerts to enhance performance of the tele-critical care medical environment.

OBJECTIVE: Identify opportunities to improve the interaction between clinicians and Tele-Critical Care (Tele-CC) programs through an analysis of alert occurrence and reactivation in a specific Tele-CC application. MATERIALS AND METHODS: Data were collected automatically through the Philips eCaremanager® software system used at multiple hospitals in the Avera health system. We evaluated the distribution of alerts per patient, frequency of alert types, time between consecutive alerts, and Tele-CC clinician choice of alert reactivation times. RESULTS: Each patient generated an average of 79.8 alerts during their ICU stay (median 31.0; 25th - 75th percentile 10.0-89.0) with 46.4 for blood pressure and 38.4 for oxygenation. The most frequent alerts for continuous physiological parameters were: MAP limit (28.9 %), O2/RR (26.4 %), MAP trend (16.5 %), HR trend (12.1 %), and HR limit (11.3 %). The median time between consecutive alerts for one parameter was less than 10 min for 86 % of patients. Tele-CC providers responded to all alert types with immediate reactivation 47-88 % of the time. Limit alerts had longer reactivation times than their trend alert counterparts (p-value < .001). CONCLUSIONS: The alert type specific differences in frequency, time occurrence and provider choice of reactivation time provide insight into how clinicians interact with the Tele-CC system. Systems engineering enhancements to Tele-CC software algorithms may reduce alert burden and thereby decrease clinicians' cognitive workload for alert assessment. Further study of Tele-CC alert generation, alert presentation to clinicians, and the clinicians' options to respond to these alerts may reduce provider workload, minimize alert desensitization, and optimize the ability of Tele-CC clinicians to provide efficient and timely critical care management.

Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis.

BACKGROUND: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations. RESEARCH QUESTION: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. STUDY DESIGN AND METHODS: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. RESULTS: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001. INTERPRETATION: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial.

BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. COPD is frequently punctuated by acute exacerbations that are precipitated primarily by infections, which increase both morbidity and mortality and inflates healthcare costs. Despite the significance of exacerbations, little understanding of immune function in COPD exacerbations exists. Natural killer (NK) cells are important effectors of innate and adaptive immune responses to pathogens and NK cell function is altered in smokers and COPD. Using high-dimensional flow cytometry, we phenotyped peripheral blood NK cells from never smokers, smokers, and COPD patients and employed a non-supervised clustering algorithm to define and detect changes in NK cell populations. We identified greater than 1,000 unique NK cell subpopulations across patient groups and describe 13 altered NK populations in patients who experienced prior exacerbations. Based upon cluster sizes and associated fluorescence data, we generated a logistic regression model to predict patients with a history of exacerbations with high sensitivity and specificity. Moreover, highly enriched NK cell subpopulations implicated in the regression model exhibited enhanced effector functions as defined by in vitro cytotoxicity assays. These novel data reflect the effects of smoking and disease on peripheral blood NK cell phenotypes, provide insight into the potential immune pathophysiology of COPD exacerbations, and indicate that NK cell phenotyping may be a useful and biologically relevant marker to predict COPD exacerbations.

Utilized or Underutilized: A Qualitative Analysis of Building Coherence During Early Implementation of a Tele-Intensive Care Unit.

Background: Generating, reading, or interpreting data is a component of Telemedicine-Intensive Care Unit (Tele-ICU) utilization that has not been explored in the literature. Introduction: Using the idea of "coherence," a construct of Normalization Process Theory, we describe how intensive care unit (ICU) and Tele-ICU staff made sense of their shared work and how they made use of Tele-ICU together. Materials and Methods: We interviewed ICU and Tele-ICU staff involved in the implementation of Tele-ICU during site visits to a Tele-ICU hub and 3 ICUs, at preimplementation (43 interviews with 65 participants) and 6 months postimplementation (44 interviews with 67 participants). Data were analyzed using deductive coding techniques and lexical searches. Results: In the early implementation of Tele-ICU, ICU and Tele-ICU staff lacked consensus about how to share information and consequently how to make use of innovations in data tracking and interpretation offered by the Tele-ICU (e.g., acuity systems). Attempts to collaborate and create opportunities for utilization were supported by quality improvement (QI) initiatives. Discussion: Characterizing Tele-ICU utilization as an element of a QI process limited how ICU staff understood Tele-ICU as an innovation. It also did not promote an understanding of how the Tele-ICU used data and may therefore attenuate the larger promise of Tele-ICU as a potential tool for leveraging big data in critical care. Conclusions: Shared data practices lay the foundation for Tele-ICU program utilization but raise new questions about how the promise of big data can be operationalized for bedside ICU staff.

COPD Care Bundle in Emergency Department Observation Unit Reduces Emergency Department Revisits.

BACKGROUND: COPD exacerbations lead to accelerated decline in lung function, poor quality of life, and increased mortality and cost. Emergency department (ED) observation units provide short-term care to reduce hospitalizations and cost. Strategies to improve outcomes in ED observation units following COPD exacerbations are needed. We sought to reduce 30-d ED revisits for COPD exacerbations managed in ED observation units through implementation of a COPD care bundle. The study setting was an 800-bed, academic, safety-net hospital with 700 annual ED encounters for COPD exacerbations. Among those discharged from ED observation unit, the 30-d all-cause ED revisit rate (ie, the outcome measure) was 49% (baseline period: August 2014 through September 2016). METHODS: All patients admitted to the ED observation unit with COPD exacerbations were included. A multidisciplinary team implemented the COPD bundle using iterative plan-do-study-act cycles with a goal adherence of 90% (process measure). The bundle, adopted from our inpatient program, was developed using care-delivery failures and unmet subject needs. It included 5 components: appropriate inhaler regimen, 30-d inhaler supply, education on devices available after discharge, standardized discharge instructions, and a scheduled 15-d appointment. We used statistical process-control charts for process and outcome measures. To compare subject characteristics and process features, we sampled consecutive patients from the baseline (n = 50) and postbundle (n = 83) period over 5-month and 7-month intervals, respectively. Comparisons were made using t tests and chi-square tests with P < .05 significance. RESULTS: During baseline and postbundle periods, 410 and 165 subjects were admitted to the ED observation unit, respectively. After iterative plan-do-study-act cycles, bundle adherence reached 90% in 6 months, and the 30-d ED revisit rate declined from 49% to 30% (P = .003) with a system shift on statistical process-control charts. There was no difference in hospitalization rate from ED observation unit (45% vs 51%, P = .16). Subject characteristics were similar in the baseline and postbundle periods. CONCLUSIONS: Reliable adherence to a COPD care bundle reduced 30-d ED revisits among those treated in the ED observation unit.

Metoprolol for the Prevention of Acute Exacerbations of COPD.

BACKGROUND: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. METHODS: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol. RESULTS: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. CONCLUSIONS: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).

Pragmatic Challenge of Sustainability: Long-Term Adherence to COPD Care Bundle Maintains Lower Readmission Rate.

Long-term sustainability of successful improvement initiatives remains a pragmatic challenge with limited literature guidance. A chronic obstructive pulmonary disease (COPD) care bundle was developed and implemented to mitigate care-delivery failures and unmet patient needs at University of Cincinnati Medical Center that led to a 35% reduction in 30-day all-cause readmissions. Here, two-year outcomes and the method of achieving sustainability are presented. METHODS: After implementation of the COPD care bundle, 30-day all-cause readmissions reduced from 22.7% to 14.7%. In 2016 the project transitioned from implementation to the sustainability phase. A four-member sustainability team was formed (pulmonologist, hospitalist, respiratory therapist, and pharmacist) with clearly defined roles for monitoring and facilitating sustainability actions. The process of bundle delivery was purposefully designed for higher reliability. Staff education and daily operations were updated to incorporate the new process. Outcome (readmission rate) and process (bundle adherence) measures were monitored monthly. Any significant drop (special cause variation) would be reviewed by the team and further action taken, if needed. The National Health Service sustainability model was used, with adjustments made to meet our contextual needs. RESULTS: The 30-day all-cause readmission rate remained the same as during the initial implementation phase (14.9%). Adherence to COPD care bundle components was 87.7%. During the two-year period, three occasions triggered a team discussion and detailed review. CONCLUSION: Sustainability requires a purposefully designed, resilient process; standard work; engagement of the team and leadership; and a monitoring system of key process and outcome measures. Application of sustainability models should be adjusted for specific contextual needs.

The anti-sigma factor MucA of Pseudomonas aeruginosa: Dramatic differences of a mucA22 vs. a ΔmucA mutant in anaerobic acidified nitrite sensitivity of planktonic and biofilm bacteria in vitro and during chronic murine lung infection.

Mucoid mucA22 Pseudomonas aeruginosa (PA) is an opportunistic lung pathogen of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients that is highly sensitive to acidified nitrite (A-NO2-). In this study, we first screened PA mutant strains for sensitivity or resistance to 20 mM A-NO2- under anaerobic conditions that represent the chronic stages of the aforementioned diseases. Mutants found to be sensitive to A-NO2- included PA0964 (pmpR, PQS biosynthesis), PA4455 (probable ABC transporter permease), katA (major catalase, KatA) and rhlR (quorum sensing regulator). In contrast, mutants lacking PA0450 (a putative phosphate transporter) and PA1505 (moaA2) were A-NO2- resistant. However, we were puzzled when we discovered that mucA22 mutant bacteria, a frequently isolated mucA allele in CF and to a lesser extent COPD, were more sensitive to A-NO2- than a truncated ΔmucA deletion (Δ157-194) mutant in planktonic and biofilm culture, as well as during a chronic murine lung infection. Subsequent transcriptional profiling of anaerobic, A-NO2--treated bacteria revealed restoration of near wild-type transcript levels of protective NO2- and nitric oxide (NO) reductase (nirS and norCB, respectively) in the ΔmucA mutant in contrast to extremely low levels in the A-NO2--sensitive mucA22 mutant. Proteins that were S-nitrosylated by NO derived from A-NO2- reduction in the sensitive mucA22 strain were those involved in anaerobic respiration (NirQ, NirS), pyruvate fermentation (UspK), global gene regulation (Vfr), the TCA cycle (succinate dehydrogenase, SdhB) and several double mutants were even more sensitive to A-NO2-. Bioinformatic-based data point to future studies designed to elucidate potential cellular binding partners for MucA and MucA22. Given that A-NO2- is a potentially viable treatment strategy to combat PA and other infections, this study offers novel developments as to how clinicians might better treat problematic PA infections in COPD and CF airway diseases.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

RATIONALE: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. OBJECTIVES: To identify patient characteristics at the time of oxygen initiation associated with its adherence. METHODS: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0-10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0-30 days), medium-term (months 9-12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. RESULTS: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40) and 94% (OR 1.94, 95% CI 1.45-2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90-31.79; intermittent, OR 38.08, 95% CI 6.96-208.20). CONCLUSIONS: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.