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.

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.).

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.

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.

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.

A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.

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 [Spo2], 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, Spo2 ≥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 .).

NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or TLR ligands. In this article, we show that the activating receptor NKG2D is a key mediator for CS-stimulated NK cell hyperresponsiveness, because CS-exposed NKG2D-deficient mice (Klrk1(-/-)) did not exhibit enhanced effector functions as assessed by cytokine responsiveness. NK cell cytotoxicity against MHC class I-deficient targets was not affected in a COPD model. However, NK cells from CS-exposed mice exhibit greater cytotoxic activity toward cells that express the NKG2D ligand RAET1ε. We also demonstrate that NKG2D-deficient mice exhibit diminished airway damage and reduced inflammation in a model of viral COPD exacerbation, which do not affect viral clearance. Furthermore, adoptive transfer of NKG2D(+) NK cells into CS-exposed, influenza-infected NKG2D-deficient mice recapitulated the phenotypes observed in CS-exposed, influenza-infected wild-type mice. Our findings indicate that NKG2D stimulation during long-term CS exposure is a central pathway in the development of NK cell hyperresponsiveness and influenza-mediated exacerbations of COPD.

Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost.

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.

Dynamic hyperinflation correlates with exertional oxygen desaturation in patients with chronic obstructive pulmonary disease.

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.

A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial.

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.

Patient reported determinants of health: a qualitative analysis of veterans with chronic obstructive pulmonary disease.

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.

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. METHODS: Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. RESULTS: Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. CONCLUSION: Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Clinical characteristics, comorbidities, and response to treatment of veterans with obstructive sleep apnea, Cincinnati Veterans Affairs Medical Center, 2005-2007.

INTRODUCTION: Obstructive sleep apnea (OSA) is a common disorder that is associated with significant morbidity. Veterans may be at an elevated risk for OSA because of increased prevalence of factors associated with the development and progression of OSA. The objective of this study was to determine the clinical characteristics, comorbidities, polysomnographic findings, and response to treatment of veterans with OSA. METHODS: We performed a retrospective chart review of 596 patients undergoing polysomnography at the Cincinnati Veterans Affairs Medical Center from February 2005 through December 2007. We assessed potential correlations of clinical data with polysomnography findings and response to treatment. RESULTS: Polysomnography demonstrated OSA in 76% of patients; 30% had mild OSA, 23% moderate OSA, and 47% severe OSA. Increasing body mass index, neck circumference, Epworth Sleepiness Scale score, hypertension, congestive heart failure, and type 2 diabetes correlated with increasing OSA severity. Positive airway pressure treatment was initiated in 81% of veterans with OSA, but only 59% reported good adherence to this treatment method. Of the patients reporting good adherence, a greater proportion of those with severe OSA (27%) than with mild or moderate disease (0%-12%) reported an excellent response to treatment. CONCLUSION: The prevalence of metabolic and cardiovascular comorbidities increased with increasing OSA severity. Only 59% of treated patients reported good adherence to treatment with positive airway pressure, and response to treatment correlated with OSA severity.

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.

High prevalence of chronic obstructive pulmonary disease among veterans in the urban midwest.

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.

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.

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.

Oxygen therapy in advanced COPD: in whom does it work?

Supplemental oxygen therapy is commonly used in patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypoxemia at rest. Use of oxygen in these patients is justified by studies showing a mortality benefit. However, the use of oxygen in other patients with advanced COPD has not clearly been established. Long-term studies assessing not only mortality but also other outcomes that are important to patients and physicians such as dyspnea, health status, and exercise capacity are lacking. This article reviews the available studies of the use of supplemental oxygen in patients with less severe hypoxemia at rest during the day, hypoxemia occurring only at night, and hypoxemia occurring only with exercise. With the knowledge that studies in patients with advanced COPD and less severe hypoxemia are limited, recommendations are provided on oxygen use in these groups of patients.

Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

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.