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Robert M Burkes,1,2 Ralph J Panos1,2 1University of Cincinnati Division of Pulmonary, Critical Care, and Sleep Medicine, Cincinnati, OH, USA; 2Department of Pulmonary, Critical Care, and Sleep Medicine, Cincinnati Veterans’ Affairs Medical Center, Cincinnati, OH, USACorrespondence: Ralph J PanosCincinnati Veterans’ Affairs Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USATel +1 513-861-3100 x 7002Email ralph.panos@va.govIntroduction: Inhaled β-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. β-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.Keywords: chronic obstructive pulmonary disease, COPD, β-agonist, long-acting β-agonist, LABA, ultra long-acting β-agonist, ULABA

Ralph J Panos1,2 1Pulmonary, Critical Care, and Sleep Medicine Division, Cincinnati Veterans Affairs Medical Center, 2Pulmonary, Critical Care, and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, OH, USA Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and its treatment is critical to improve quality of life, reduce symptoms, and diminish the frequency of COPD exacerbations. Due to the harmful environmental effects of pressurized metered-dose inhalers (pMDIs) containing chlorofluorocarbons (CFCs), newer systems for delivering respiratory medications have been developed. Methods: A search of the literature in the PubMed database was undertaken using the keywords “COPD,” “albuterol,” “ipratropium bromide,” and “Respimat® Soft Mist Inhaler™”; pertinent references within the identified citations were included. The environmental effect of CFC-pMDIs, the invention of the Respimat® Soft Mist Inhaler™ (SMI) (Boehringer Ingelheim, Ingelheim, Germany), and its use to deliver the combination of albuterol and ipratropium bromide for the treatment of COPD were reviewed. Results: The adverse environmental effects of CFC-pMDIs stimulated the invention of novel delivery systems including the Respimat SMI. This review presents its development, internal mechanism, and use to deliver the combination of albuterol and ipratropium bromide. Conclusion: CFC-pMDIs contributed to the depletion of the ozone layer and the surge in disorders caused by harmful ultraviolet B radiation. The banning of CFCs spurred the development of novel delivery systems for respiratory medications. The Respimat SMI is an innovative device that produces a vapor of inhalable droplets with reduced velocity and prolonged aerosol duration that enhance deposition within the lower airway and is associated with improved patient satisfaction. Clinical trials have demonstrated that the Respimat SMI can achieve effects equivalent to pMDIs but with lower medication doses. The long-term safety and efficacy remain to be determined. The Respimat SMI delivery device is a novel, efficient, and well-received system for the delivery of aerosolized albuterol and ipratropium bromide to patients with COPD; however, the presence of longer-acting, less frequently dosed respiratory medications provide patients and providers with other therapeutic options. Keywords: Respimat® Soft Mist Inhaler™, COPD, pressurized metered-dose inhaler, chlorofluorocarbons

Daniel E Murphy,1,2 Ralph J Panos1,2 1Pulmonary, Critical Care and Sleep Medicine Division, Cincinnati Veterans Affairs Medical Center, 2Pulmonary, Critical Care and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, OH, USA Abstract: Chronic obstructive pulmonary disease (COPD) is frequently under-recognized and underdiagnosed. To determine the natural history of recognized and unrecognized COPD, we studied the rate of diagnosis, health care utilization, and mortality in patients with airflow limitation (AFL). Three hundred forty-seven outpatients at the Cincinnati Veterans Administration Medical Center performed spirometry and completed a respiratory questionnaire. Patients were followed for a minimum of 30 months and medical records were reviewed for COPD diagnosis, mortality, respiratory-related health care utilization, comorbidities, and respiratory medications. Three hundred twenty-five of 347 (94%) patients performed technically adequate spirometry and completed questionnaires. When AFL was defined by fixed ratio (FR, forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] < 0.7), patients with AFL and a diagnosis of COPD had a higher annual mortality rate (7.1% ± 2% versus 2.4% ± 0.8%, P = 0.01), more hospitalizations per year (0.2 ± 0.06 versus 0.04 ± 0.01, P < 0.001 mean ± standard error of the mean), increased respiratory symptoms (12.0 ± 0.9 versus 7.2 ± 0.6, P < 0.0001), and higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage compared with undiagnosed patients. Ninety-two of 137 patients with AFL (67%) had unrecognized AFL; 16 (17%) of the 92 were subsequently diagnosed. When AFL was defined by the lower limit of normal (LLN, FEV1/FVC < LLN), 67 of 103 patients (65%) had unrecognized AFL; 12 (18%) of the 67 were subsequently diagnosed. Patients with AFL defined by FR who were subsequently diagnosed had more emergency department visits per year (0.33 ± 0.11 versus 0.11 ± 0.05, P = 0.009), increased respiratory symptoms (10.2 ± 1.6 versus 6.5 ± 0.7, P < 0.05), and higher GOLD stage, but similar mortality and hospitalizations compared with the persistently undiagnosed patients. The annual rate of documented COPD diagnosis was 7% for both FR and LLN definitions. Patients with AFL and a diagnosis of COPD have more severe disease, higher health care utilization, and mortality than undiagnosed patients. The annual rate of COPD diagnosis is 7% among individuals with unrecognized AFL. Worse AFL, increased respiratory symptoms, and ED visits are associated with a subsequent COPD diagnosis in individuals with unrecognized AFL. Keywords: COPD, diagnosis, airflow limitation, Veterans Healthcare Administration

Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.Design: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans Affairs hospital-based outpatient clinics.Participants: Patients hospitalized for COPD in the past year.Intervention: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size.Measurements: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy.Results: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053).Limitations: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited.Conclusion: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions. [ABSTRACT FROM AUTHOR]

Long-term use of supplemental oxygen improves survival in patients with COPD and severe resting hypoxemia. However, the role of oxygen in symptomatic patients with COPD and more moderate hypoxemia at rest and desaturation with activity is unclear. The few long-term reports of supplemental oxygen in this group have been of small size and insufficient to demonstrate a survival benefit. Short-term trials have suggested beneficial effects other than survival in patients with COPD and moderate hypoxemia at rest. In addition, supplemental oxygen appeared to improve exercise performance in small short-term investigations of patients with COPD and moderate hypoxemia at rest and desaturation with exercise, but long-term trials evaluating patient-reported outcomes are lacking. This article reviews the evidence for long-term use of supplemental oxygen therapy and provides a rationale for the National Heart, Lung, and Blood Institute Long-term Oxygen Treatment Trial. The trial plans to enroll subjects with COPD with moderate hypoxemia at rest or desaturation with exercise and compare tailored oxygen therapy to no oxygen therapy. [ABSTRACT FROM AUTHOR]

Although chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality within the Veterans Health care Administration, its prevalence and recognition are not known. We measured airflow limitation and diagnosed COPD at the Cincinnati Veteran's Administration Medical Center. Participants were 326 outpatients who performed spirometry and completed questionnaires. Health care-provider-diagnosis and self-diagnosis of COPD were compared with COPD defined by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.7 (fixed ratio) and (FEV1/FVC)/lower limit of normal (LLN) < 1.0. COPD prevalence was 43% (95% confidence interval: 36.9, 48.1) by fixed ratio and 33% (95% confidence interval: 27.2, 36.8) by LLN. Eighteen percent of the patients had health care-provider-recorded and 23% had self-reported diagnoses of COPD. Positive predictive values for the diagnosis of COPD were 79% and 64% for healthcare providers versus 68% and 62% for patients; negative predictive values were 64% and 74% for healthcare providers versus 64% and 76% for patients (fixed ratio and LLN, respectively). COPD prevalence is higher among Cincinnati veterans than among general U.S. population. COPD is under-recognized by both health care providers and veterans. [ABSTRACT FROM AUTHOR]

Pulmonary rehabilitation is an effective therapy that improves day-to-day symptoms and quality of life in patients with chronic obstructive pulmonary disease. In this review, we look at the role of virtual programs, implementation of artificial intelligence, emerging areas of improvement within the educational components of programs, and the benefit of advanced practice providers in directorship roles., Competing Interests: None declared., (Thieme. All rights reserved.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Drs Zafar and Panos are the co-inventors of the o-PEP device and are the owners of PEP Buddy LLC. The University of Cincinnati Institutional Review Board has approved their involvement in this study. The remaining authors have disclosed no conflicts of interest.

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 P CO 2 (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., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

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., (JCOPDF © 2021.)

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 mm 2 that increased to 170 mm 2 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., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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, FEV 1 %, and body mass index of 59.8 (±9.5) years, 35 (±24)%, and 28.8 (±8) m 2 /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., (© 2020 by the Society for Academic Emergency Medicine.)

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., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

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 %), O 2 /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., Competing Interests: Declaration of Competing Interest Omar Badawi is an employee at Philips. The remaining authors have no competing interests to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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 (FEV 1 ) 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.)., (Copyright © 2019 Massachusetts Medical Society.)

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., (Copyright © 2019 The Joint Commission. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The effect of ICU telemedicine on transfers is not well studied. This study tests the hypothesis that ICU telemedicine decreases ICU patient interhospital transfers., Methods: Data were retrieved for patients admitted to 306 Veterans Affairs ICUs in 117 acute care facilities between 2011 and 2015. Telemedicine was provided to 52 ICUs in 23 acute care facilities by two support centers located in Minneapolis and Cincinnati. We compared interhospital transfer rates in ICU telemedicine-affiliated hospitals with transfer rates of facilities with no telemedicine program. We used generalized linear mixed multivariable models to assess the association of ICU telemedicine with transfer rates and 30-day mortality., Results: A total of 553,523 admissions to Veterans Affairs ICUs (97,256 to telemedicine hospitals; 456,267 to non-telemedicine hospitals) were analyzed. Transfers decreased from 3.46% to 1.99% in the telemedicine hospitals and from 2.03% to 1.68% in the non-telemedicine facilities between pre- and post-telemedicine implementation periods (P < .001). After adjusting for demographics, illness severity, admission diagnosis, and facility, ICU telemedicine was associated with overall reduced transfers with a relative risk (RR) of 0.79 (95% CI, 0.71-0.87; P < .001); this reduction occurred in patients with moderate (RR, 0.77; 95% CI, 0.61-0.98; P =.034), moderate to high (RR, 0.79; 95% CI, 0.63-0.98; P =.035), and high illness severity (RR, 0.73; 95% CI, 0.60-0.90; P =.003) and in nonsurgical patients (RR, 0.82; 95% CI, 0.73-0.92; P =.001). Transfers decreased in patients admitted with GI (RR, 0.55; 95% CI, 0.41-0.74, P < .001) and respiratory admission diagnoses (RR, 0.52; 95% CI, 0.38-0.71; P < .001). ICU telemedicine was not associated with an increase in 30-day mortality., Conclusions: ICU telemedicine was associated with a decrease in interhospital ICU transfers., (Published by Elsevier Inc.)

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are chronic pulmonary diseases that affect ~70,000 and 251 million individuals worldwide, respectively. Although these two diseases have distinctly different pathophysiologies, both cause chronic respiratory insufficiency that erodes quality of life and causes significant morbidity and eventually death. In both CF and COPD, the respiratory microbiome plays a major contributing role in disease progression and morbidity. Pulmonary pathogens can differ dramatically during various stages of each disease and frequently cause acute worsening of lung function due to disease exacerbation. Despite some similarities, outcome and timing/type of exacerbation can also be quite different between CF and COPD. Given these clinical distinctions, both patients and physicians should be aware of emerging therapeutic options currently being offered or in development for the treatment of lung infections in individuals with CF and COPD. Although interventions are available that prolong life and mitigate morbidity, neither disorder is curable. Both acute and chronic pulmonary infections contribute to an inexorable downward course and may trigger exacerbations, culminating in loss of lung function or respiratory failure. Knowledge of the pulmonary pathogens causing these infections, their clinical presentation, consequences, and management are, therefore, critical. In this review, we compare and contrast CF and COPD, including underlying causes, general outcomes, features of the lung microbiome, and potential treatment strategies.

Background: Readmissions of chronic obstructive pulmonary disease (COPD) have devastating effects on patient quality-of-life, disease progression and healthcare cost. Effective interventions to reduce COPD readmissions are needed., Objectives: Reduce 30-day all-cause readmissions by (1) creating a COPD care bundle that addresses care delivery failures, (2) using improvement science to achieve 90% bundle adherence., Setting: An 800-bed academic hospital in Ohio, USA. The COPD 30-day all-cause readmission rate was 22.7% from August 2013 to September 2015., Method: We performed a cross-sectional study of COPD 30-day readmissions from October 2014 to March 2015 to identify care delivery failures. We interviewed readmitted patients with COPD to identify their needs after discharge. A multidisciplinary team created a care bundle designed to mitigate system failures. Using a quasi-experimental study and 'Model for Improvement', we redesigned care delivery to improve bundle adherence. We used statistical process control charts to analyse bundle adherence and all-cause 30-day readmissions., Results: Cross-sectional review of the index (first-time) admissions revealed COPD was the most common readmission diagnosis and identified 42 system-level failures. The most prevalent failures were deficient inhaler regimen at discharge, late or non-existent follow-up appointments, and suboptimal discharge instructions. Patient interviews revealed confusing discharge instructions, especially regarding inhaler use. The COPD care-bundle components were: (1) appropriate inhaler regimen, (2) 30-day inhaler supply, (3) inhaler education on the device available postdischarge, (4) follow-up within 15 days (5) standardised patient-centred discharge instructions. The adherence to completing bundle components reached 90% in 5.5 months and was sustained. The COPD 30-day readmission rate decreased from 22.7% to 14.7%. Patients receiving all bundle components had a readmission rate of 10.9%. As a balancing measure for the targeted reduction in readmission rate, we assessed length of stay, which did not change (4.8 days before vs 4.6 days after; p=0.45)., Conclusion: System-level failures and unmet patient needs are modifiable risks for readmissions. Development and reliable implementation of a COPD care bundle that mitigates these failures reduced COPD readmissions., Competing Interests: Competing interests: The authors have no conflict of interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Positive expiratory pressure(PEP) breathing modalities are commonly prescribed in obstructive lung diseases, however practical methods of airway pressures(AP) quantification for therapeutic efficacy are lacking. Excessive dynamic airway collapse(EDAC) is characterized by expiratory central airway collapse leading to dyspnea and poor quality of life(QoL), with limited therapeutic options., Purpose: To measure AP and exertional dyspnea in EDAC patients during normal breathing and with use of pursed-lip breathing(PLB), nasal PEP device(nPEP), and oral-PEP valve(oPEP) during rest and exercise using an Esophageal Manometer., Methods: EDAC patients exercised on a bicycle ergometer sequentially using normal breathing, PLB, nPEP, and oPEP for five-minute intervals. AP's were measured by continuous topographic upper airway manometry. Pre- and post-exercise BORG dyspnea scores were recorded and QoL measured with the St. George's respiratory questionnaire(SGRQ-C). The most effective and patient-preferred PEP modality was prescribed for daily activities and SGRQ-C repeated after one week., Results: Three women with symptomatic EDAC participated. Expiratory laryngopharyngeal AP's during exercise with normal breathing, PLB, nPEP and oPEP in patient-1 were 1.7, 14, 4.5, and 7.3 mmHg, in patient-2; 2.3, 8, 8.3, and 12 mmHg, and in patient-3; 1, 15, unobtainable, and 9 mmHg, respectively. Maximal reduction in BORG scores occurred with PLB in patient 1 and with oPEP in patients 2 and 3. After 1 week mean SGRQ-C scores declined by 17-points., Conclusions: Upper airway manometry directly measures laryngopharyngeal pressures during rest and exercise and can be used to select and optimize PEP breathing techniques to improve respiratory symptoms in EDAC patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Given the complexity of high-acuity health care, designing an effective clinical note template can be beneficial to both document patient care and clarify how telemedicine is used. We characterized documented interactions via a standardized note template between bedside intensive care unit (ICU) providers and teleintensivists in 2 Veterans Health Administration ICU telemedicine support centers. All ICUs linked to support centers and providing care from October 2012 through September 2014 were considered. Interactions were assessed based on initiation site, bedside initiator, contact type, and patient care change. Of 14 511 ICU admissions with teleintensivist access, teleintensivist interaction was documented in 21.6% (N = 3136). In particular, contacts were primarily initiated by bedside staff (74.4%), use increased over time, and of contacts resulting in changes in patient care, most were initiated by a bedside nurse (84.3%). Given this variation, future research necessitates inclusion of utilization in evaluation of Tele-ICU and patient outcomes., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

Background: Although inhaled medications are effective therapies for COPD, many patients and providers use them incorrectly., Methods: We recruited providers who prescribe inhalers or teach inhaler technique and assessed their use of metered-dose inhalers (MDIs), various dry powder inhalers (DPIs), and Respimat using predefined checklists. Then they watched tablet-based multimedia educational videos that demonstrated correct inhaler technique by a clinical pharmacist with teach-back from a patient and were re-evaluated. We also recruited patients with COPD and assessed their use of their prescribed inhalers and then retested them after 3-6 months. Baseline and follow-up respiratory symptoms were measured by the COPD Assessment Test., Results: Fifty-eight providers and 50 subjects participated. For all providers, correct inhaler technique (reported as percentage correct steps) increased after the videos: MDI without a spacer (72% vs 97%) MDI with a spacer (72% vs 96%), formoterol DPI (50% vs 94%), mometasone DPI (43% vs 95%), tiotropium DPI (73% vs 99%), and Respimat (32% vs 93%) (before vs after, P < .001 for all comparisons). Subjects also improved their inhaler use technique after viewing the educational videos: MDI without a spacer (69% vs 92%), MDI with a spacer (73% vs 95%), and tiotropium DPI (83% vs 96%) (before vs after, P < .001 for all comparisons). The beneficial effect of this educational intervention declined slightly for subjects but was durably improved after several months. COPD Assessment Test scores did not demonstrate any change in respiratory symptoms., Conclusions: A tablet-based inhaler education tool improved inhaler technique for both providers and subjects. Although this intervention did show durable efficacy for improving inhaler use by patients, it did not reduce their respiratory symptoms., (Copyright © 2017 by Daedalus Enterprises.)

Introduction: Long acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction by antagonizing para-sympathetic bronchoconstricting effects within the airways. For years, tiotropium, has been the cornerstone LAMA for chronic obstructive pulmonary disease (COPD) management. Recently, new agents, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide, have been developed and introduced into clinical practice. Areas covered: This article reviews the clinical efficacy and adverse effects of currently available LAMAs in COPD treatment as well as developing LAMAs in early clinical trials and preclinical studies (V0162, TD-4208, CHF 5407, AZD9164, AZD8683, bencycloquidium). In addition, a new class of molecule that combines muscarinic antagonist and β2-adrenergic properties (MABA) is described and current developmental progress discussed (GSK-961081, THRX-200495). Expert opinion: Future key areas for developing drugs for the management of COPD include prolonged duration of action, optimal delivery systems, synergistic combinations with other drugs, maximization of benefits and minimization of adverse effects. The development of new LAMA and MABA molecules provides exciting progress towards simpler and more effective COPD management.

Background: The predictive characteristics of different screening surveys for the recognition of individuals at risk for airflow obstruction (AFO) have not been evaluated simultaneously in the same population., Purpose: To compare five AFO/COPD screening questionnaires., Methods: 383 individuals completed the Veterans Airflow Obstruction Screening Questionnaire, Personal Level Screener for COPD (VAFOSQ), the 11-Q COPD Screening Questionnaire (11-Q), the COPD Population Screener (COPD-PS) and the Lung Function Questionnaire (LFQ) and performed spirometry. AFO was defined as forced expiratory volume in one second divided by the forced vital capacity (FEV 1 /FVC) < 0.7, fixed ratio (FR) or FEV 1 /FVC < lower limit of normal (LLN). The predictive characteristics of the five questionnaires were calculated and non-parametric receiver operating characteristic (ROC) curves estimated by logistic regression., Results: 376 participants completed at least two of the questionnaires and performed technically acceptable spirometry. AFO was present in 102 (27.1%) and 150 (39.9%) based on LLN and FR, respectively. The number of individuals positively selected by the VAFOSQ was 227, PLS 128, 11-Q 236, COPD-PS 217, and LFQ 328. The area under the ROC curves for the questionnaires was between 0.60 and 0.66 (LLN) and 0.58 and 0.66 (FR)., Conclusions: Although these screening surveys have acceptable and similar predictive ability for the identification of AFO, their published thresholds lead to substantially different classification rates. The choice of an appropriate threshold for the identification of individuals with possible AFO/COPD should consider the underlying prevalence of AFO/COPD in the target population and the relative costs of misclassifying affected and unaffected cases., Clinical Trial Registration: None., Primary Source of Funding: Veterans Health Administration., (Published by Elsevier Ltd.)

Background: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation., Methods: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo 2 ], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo 2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked., Results: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes., Conclusions: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .).

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality within the Veterans Healthcare Administration (VHA) and is frequently under-diagnosed. We developed the Veterans Airflow Screening Questionnaire (VAFOSQ) to improve the identification of Veterans with airflow obstruction (AFO), the most commonly used criterion for the diagnosis of COPD.We created an initial survey with 78 variables that have been associated with AFO. A total of 825 patients in 3 primary care clinics performed spirometry after bronchodilator administration and completed the initial survey. Best sets regression was used to build a model that predicted AFO optimally. A total of 195 of 825 (23.3%) patients had AFO and 7 items positively predicted AFO. When the questionnaire score was greater than 25, the VAFOSQ accurately identified AFO with an area under the receiver operating curve of 0.72. In a prospective validation cohort of 376 participants, the positive predictive value was 32% and negative predictive value 81%. The VAFOSQ is a reliable and valid instrument for the identification of veterans at risk for AFO who would benefit from further evaluation with spirometry and assessment for COPD. The VAFOSQ is straightforward to use and can be easily self-administered and self-scored enabling widespread application within the VHA., Competing Interests: The authors have no relevant interests to declare.

Introduction: Phosphodiesterase (PDE) inhibitors modulate lung inflammation and cause bronchodilation by increasing intracellular cyclic adenosine 3', 5'-monophosphate in airway smooth muscle and inflammatory cells. Roflumilast is the only approved PDE-4 inhibitor (PDE4I) for use in chronic obstructive pulmonary disease (COPD). Its beneficial clinical effects occur preferentially in patients with chronic bronchitis and frequent COPD exacerbations. Use of roflumilast as adjunctive or alternate therapy to other COPD medications reduces exacerbations and modestly improves lung function., Areas Covered: This article reviews the current role of PDE4I in COPD treatment emphasizing roflumilast's clinical efficacy and adverse effects. This article also reviews developing PDE4Is in early clinical trials and in preclinical studies., Expert Opinion: After decades of research in drug development, PDE4Is are a welcomed addition to the COPD therapeutic armamentarium. In its current clinical role, the salubrious clinical effects of PDE4I in reducing exacerbations and stabilizing the frequent exacerbator phenotype have to be cautiously balanced with numerous adverse effects. Developing drugs may provide similar or better clinical benefits while minimizing adverse effects by changing the mode of drug delivery to inhaled formulations, combining dual PDE isoenzyme inhibitors (PDE1/4I and PDE3/4I) and by forming hybrid molecules with other bronchodilators (muscarinic receptor antagonist/PDE4I and β2-agonist/PDE4I).

Introduction: For the last two decades, long-acting β agonists (LABAs) have been a cornerstone in the management of chronic obstructive pulmonary disease (COPD). They relax airway smooth muscle and augment expiratory airflow, which reduces hyperinflation and improves dyspnea, functional capacity and quality of life. In recent years, Indacaterol, a LABA with an ultra-long duration of action (ultra-LABA), which only requires once-daily dosing, was approved by the FDA. The clinical efficacy of indacaterol is comparable, and, in some aspects better, than the currently available LABAs., Areas Covered: This article reviews the pharmacological properties, clinical efficacy, safety and potential role of the ultra-LABAs in COPD management., Expert Opinion: Ultra-LABAs are effective bronchodilators with a prolonged duration of action. By decreasing dosing frequency, ultra-LABAs potentially may improve respiratory medication adherence, which is associated with better survival and less healthcare utilization. In addition to their salubrious benefits, β agonists may produce untoward effects. Increased mortality and hospitalizations among patients with left ventricular heart failure, who were treated with β agonists, has caused concern about their use in patients with COPD and heart disease. Further experience and testing will determine the optimal role of ultra-LABAs in the management of COPD.

Purpose: To measure respiratory health and respiratory-related (RR) health care utilization in veterans with chronic obstructive pulmonary disease referred to pulmonary rehabilitation (PR) at the Cincinnati Veterans Administration (VA) Medical Center., Methods: We reviewed the records of 430 patients referred for PR from 2008 to 2010: 78 met inclusion criteria and completed PR (PR group); 92 qualified for PR but declined participation (referral group). All PR participants completed the St. George's Respiratory Questionnaire (SGRQ), BODE index, 6-minute walk test (6MWT), UCSD Shortness of Breath Questionnaire (UCSDSOBQ), Pulmonary Disease Knowledge Test, and self-reported use of short-acting bronchodilators before and after PR. All VA health care encounters during the 12 months before and after PR (PR group) or referral (referral group) were reviewed., Results: Respiratory health improved after PR: SGRQ (60.6 ± 15.1, 51.1 ± 16.7), BODE (4.65 ± 1.93, 3.41 ± 1.84), 6MWT (497 ± 367 m, 572 ± 397 m), UCSDSOBQ (68.3 ± 21.1, 61.0 ± 20.9), Pulmonary Disease Knowledge Test (75.9 ± 12.4%, 85.9 ± 11.1%), short-acting bronchodilator (22.5 ± 25.3, 12.8 ± 15.6 inhalations per week) (before, after PR; P < .001 for all comparisons). The RR emergency department (ED) visits (0.71 ± 1.44, 0.44 ± 0.86; P = .04) and RR hospitalizations (0.41 ± 0.73, 0.23 ± 0.51; P = .03) (visits/patient/year; pre-PR, post-PR) decreased following PR. RR ED visits and hospitalizations were the same for the PR and referral groups prior to PR but declined post-PR (0.44 ± 0.86, 0.78 ± 1.36 ED visits/patient/year; P = .05) and (0.23 ± 0.51, 0.59 ± 1.20 hospitalizations/patient/year; P = .01). Ninety-four percent of PR participants achieved the minimal clinically important difference in at least 1 univariate scale (Modified Medical Research Council, UCSDSOBQ, SGRQ, and 6MWT); 82%, 2 scales; 59%, 3 scales; and 24%, all 4 scales., Conclusions: Pulmonary rehabilitation improves respiratory health in veterans with chronic obstructive pulmonary disease and decreases RR health care utilization.

Chronic obstructive pulmonary disease (COPD), a disease manifested by significantly impaired airflow, afflicts ∼14.2 million cases in the United States alone with an estimated 63 million people world-wide. Although there are a number of causes, the predominant cause is excessive tobacco smoke. In fact, in China, there have been estimates of 315,000,000 people that smoke. Other less frequent causes are associated with indirect cigarette smoke, air pollutants, biomass fuels, and genetic mutations. COPD is often associated with heart disease, lung cancer, osteoporosis and conditions can worsen in patients with sudden falls. COPD also affects both innate and adaptive immune processes. Cigarette smoke increases the expression of matrix metalloproteases and proinflammatory chemokines and increases lung titers of natural killer cells and neutrophils. Yet, neutrophil reactive oxygen species (ROS) mediated by the phagocytic respiratory burst and phagocytosis is impaired by nicotine. In contrast to innate immunity in COPD, dendritic cells represent leukocytes recruited to the lung that link the innate immune responses to adaptive immune responses by activating naïve T cells through antigen presentation. The autoimmune process that is also a significant part of inflammation associated with COPD. Moreover, coupled with restricted FEV1 values, are the prevalence of patients with single or multiple infections by bacteria, viruses and fungi. Finally, we focus on one of the more problematic infectious agents, the Gram-negative opportunistic pathogenic bacterium, Pseudomonas aeruginosa. Specifically, we delve into the development of highly problematic biofilm infections that are highly refractory to conventional antibiotic therapies in COPD. We offer a non-conventional, biocidal treatment that may be effective for COPD airway infections as well as with combinations of current antibiotic regimens for more effective treatment outcomes and relief for patients with COPD.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common disorder of Veterans that causes significant morbidity and mortality. To measure Veterans' perceptions about COPD, the effect of COPD on their lives and health, and their needs for improved health, we performed a postal survey., Methods: 3263 Veterans with a diagnosis of COPD who received care at the Cincinnati Veterans Affairs Medical Center in 2008 were stratified into quintiles by Veterans Health Administration-associated COPD healthcare cost and uniformly sampled., Results: 493 of 1000 surveys (49%) were completed and returned. COPD had different effects on respondents in top and bottom quintiles (highest and lowest COPD-related cost) for: knowledge of COPD diagnosis (89% vs. 73%, p = 0.03); activities affected by breathing, including work (69% vs. 45%), recreation (85% vs. 62%), change in living arrangements (36% vs 16%), and increased need for help (54% vs. 25%) (p < 0.05 for all comparisons); emotional effect of respiratory symptoms, including depression (53% vs. 30%), fear (41% vs. 15%), and helplessness (49% vs. 24%) (p < 0.05 for all comparisons). 91% of Veterans were prescribed inhalers and one-quarter had difficulties using them. 25% of Veterans did nothing when they had symptoms of an exacerbation., Conclusions: COPD has profound effects on Veterans' breathing related activities and generates many negative emotions. Primary care providers are critical in conveying the diagnosis of COPD and providing information about the disease and its management. Veterans with COPD adhere poorly to their medications, and report little instruction about COPD or its management., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: COPD is a significant cause of morbidity and mortality in the Veterans Health Administration (VHA). To determine the clinical factors associated with the cost of COPD management, we analyzed the relationship between clinical characteristics and COPD healthcare costs at the Cincinnati VAMC., Methods: We queried the VHA Decision Support System for patients diagnosed with COPD at the Cincinnati VAMC and calculated their VHA COPD-related encounters and costs in FY2008. Patients were ranked by COPD-related cost. We determined the detailed clinical characteristics of patients selected by modified systematic sampling and performed univariate and multivariable ordinary linear regression analysis to determine factors associated with cost., Results: 3263 Veterans had 11,869 encounters with a primary or secondary diagnosis of COPD: 10,032 clinic visits, 505 emergency department (ED) visits, and 1,332 hospitalizations and incurred a total COPD-related healthcare cost of $21.4 M: $2.4 M clinic visits, $0.21 M ED visits, and $18.7 M hospitalizations and $0.89 M for COPD-related prescription costs. When the patients were ranked by VHA healthcare costs, the top 20% of patients accounted for 86% of the total costs and 57% of the total encounters with a primary or secondary diagnosis code of COPD and 90% of the total costs and 75% of the total encounters with a primary diagnosis code of COPD. The clinical characteristics and VHA healthcare costs of 840 of the 3263 unique individuals with COPD were analyzed to determine those characteristics associated with increased COPD-related costs. Univariate analysis showed significant associations with 24 clinical variables; the 4 most highly associated factors were nursing home residence, total hospital admissions, use of oral corticosteroids, and supplemental oxygen (p < 0.001 for all). In multivariate analysis, total number of admissions (p < 0.001), management by a pulmonologist (p < 0.001), number of clinic visits (p < 0.001), use of short acting anticholinergic (p = 0.001), forced expiratory volume in 1 second (FEV1) (p = 0.011), number of prescriptions (p = 0.011), body mass index (BMI) (p = 0.025), and use of inhaled corticosteroid (p = 0.043) were associated with COPD management cost., Conclusion: The total number of admissions, clinic visits, physiologic impairment, BMI, number of medications, and type of provider are strongly associated with the total cost of COPD management. These factors may be used to focus COPD management toward patients with the potential for high utilization of healthcare resources.

Although COPD is a common disorder of veterans who receive care from the Veterans Healthcare Administration (VHA), the perceptions of veterans with COPD about their disease, its effects on their lives, and their interactions with the VHA have not been determined. Utilizing qualitative methodology, we conducted focus groups of veterans with COPD at the Cincinnati VA Medical Center. Participants were selected by systematic sampling from the top quintile of veterans stratified by the cost of healthcare utilization related to a primary diagnosis of COPD and grouped by age and use of supplemental oxygen. All 42 participants were male and had a mean age of 65 years. Analysis of the focus group transcripts demonstrated five major themes: 1) Physical and Functional Limitations: work and employment constraints, recreation restrictions, limits on activities of daily living, reduced sexuality, concerns about housing and finances, and physical symptoms; 2) Restricted Social Interactions/Altered Social Networks: altered relationships with friends and family and reliance upon family and care givers; 3) Emotional Effects: reduced self-worth, vulnerability, depression, perseverance and adaptation, hopelessness, fear, pride, and lack of control; 4) Limitations in the Understanding of COPD: unawareness of diagnosis, triggers and reaction to disease manifestations, COPD management; and 5) Complex Healthcare Interactions. COPD pervasively and extensively affects all aspects of veterans' lives and causes significant consequences for their care and management.

PH occurs alone or in association with many disorders. Many patients with transthoracic echocardiography (TTE) findings suggesting PH never receive additional evaluation. Patient characteristics and echocardiographic data associated with increased recognition of PH have not been fully evaluated. We evaluated TTE reports at the Cincinnati Veterans Affairs Medical Center from 2005 to 2006 retrospectively for findings highly indicative of PH: Estimated systolic pulmonary artery pressure (sPAP) ≥40 mmHg, increased right atrial or right ventricular (RV) size, or reduced RV function. Only patients with left ventricular ejection fraction (LVEF) ≥50% and no known diagnosis of PH were included. Patient characteristics, TTE findings, provider recognition rates, and subsequent referral for additional evaluation were assessed. A total of 227 of 3,960 (5.7%) TTE reports revealed findings indicating possible PH. Providers acknowledged possible PH in 53 (23.4%) reports. Recognized PH was predicted by increased RV size (odds ratio (OR) = 5.07, P < 0.001), increased right atrial dimension (OR = 6.45, P < 0.001), decreased RV function (OR = 8.86, P < 0.001), and increased PAP (OR = 1.04 corresponding to each unit increase of PAP, P < 0.01). Patients with comorbid obstructive sleep apnea (OSA), interstitial lung disease, and dyspnea were also more likely to be recognized (OR = 3.63, P = 0.021; OR = 10.98, P = 0.004; OR = 2.39, P = 0.007, respectively). The 12-month mortality rate for recognized patients, 11.3% (7/53), was lower than for unrecognized patients, 25.3% (44/174; P = 0.03). Providers recognized less than one in four patients with echocardiographic evidence suggesting PH. Echocardiography reports revealing higher PAP and right heart dilation and dysfunction are associated with increased acknowledgement of possible PH.

Background: Dynamic hyperinflation (DH) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD). Exertional desaturation (ED) also occurs commonly in COPD but neither routine physiologic parameters nor imaging predict ED accurately. In this study we evaluated the relationship between DH and ED during 6-min walk testing (6MWT)., Methods: We measured ED and DH in patients with stable COPD. SpO2 was measured by continuous pulse oximetry during 6MWT. ED was defined as a decline in SpO2 (ΔSpO2) ≥4 %. DH was determined by measuring inspiratory capacity (IC) before and after the 6MWT using a handheld spirometer. DH was defined as ΔIC >0.0 L. We correlated DH and ED with clinical and pulmonary physiologic variables by regression analysis, χ (2), and receiver operator curve (ROC) analysis., Results: Thirty males [age = 65 ± 9.4 years, FEV1 % predicted = 48 ± 14 %, and DLCO % predicted = 50 ± 21 % (mean ± SD)] were studied. ΔSpO2 correlated with ΔIC (r = 0.49, p = 0.005) and age (r = 0.39, p = 0.03) by univariate analysis; however, only ΔIC correlated on multivariate regression analysis (p = 0.01). ΔSpO2 did not correlate with FEV1, FVC, FEF25-75, RV, DLCO % predicted, BMI, smoking, BORG score, or distance covered in 6MWT. DH strongly correlated with ED (p = 0.001). On ROC analysis, DH had an area under the curve of 0.92 for the presence of ED (sensitivity = 90 %; specificity = 77 %, p < 0.001)., Conclusion: Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.