Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

COPD Exacerbations, Costs, and Health Care Resource Utilization Before and After Initiation of Fluticasone Furoate/Umeclidinium/Vilanterol in Routine Care in the USA.

Purpose: To examine the impact of initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in a single device on chronic obstructive pulmonary disease (COPD) exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related healthcare resource utilization (HCRU) and costs in patients with COPD. Methods: Retrospective database analysis of patients with COPD aged ≥40 years who initiated FF/UMEC/VI between September 1, 2017, and December 31, 2018 (index date: first pharmacy claim for FF/UMEC/VI), following evidence of multiple-inhaler triple therapy (MITT) (≥30 consecutive days) in the year prior to index. COPD exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related HCRU and costs were compared between the baseline period (12 months prior to and including index) and follow-up period (12 months following index). Results: Data from 912 patients (mean [SD] age: 71.2 [8.1], 51.2% female) were included in the analyses. Among the overall cohort, mean count of total COPD exacerbations (moderate or severe) per patient was statistically significantly lower in the follow-up period compared to baseline (1.2 vs 1.4, p=0.001). The proportion of patients with ≥1 COPD exacerbation (moderate or severe) was also statistically significantly lower in the follow-up period compared to baseline (56.4% vs 62.4%, p=0.001). All-cause and COPD-related HCRU were similar during follow-up compared to baseline, although the proportion of patients with COPD-related ambulatory visits was lower during follow-up (p<0.001). COPD-related office visit costs, emergency room visit costs, and pharmacy costs were statistically significantly lower during follow-up compared to baseline (p<0.001; p=0.019; p<0.001, respectively). Conclusion: In a real-world setting, patients on MITT who subsequently initiated FF/UMEC/VI in a single device had significant reductions in the rate of COPD exacerbations (moderate or severe). Switching to FF/UMEC/VI also resulted in improvements in some HCRU and cost outcomes. These data support the use of FF/UMEC/VI among patients at high risk of exacerbation to reduce future risk and improve outcomes.

Impact of influenza infection on the short- and long-term health of patients with chronic obstructive pulmonary disease.

BACKGROUND: Influenza is a common cause of acute respiratory infection that leads to exacerbation of underlying chronic obstructive pulmonary disease (COPD). To elucidate the short- and long-term effects of influenza in patients with COPD, we examined health care resource utilization (HRU) and costs up to 13 months following influenza infection. METHODS: We conducted a retrospective cohort study using U.S. insurance claims data from MarketScan. Patients with an influenza diagnosis during the 2012-2014 influenza seasons and continuous enrollment in a health plan from 12 months before to 13 months after the index influenza diagnosis were identified and propensity score-matched 1:5 to controls without evidence of influenza. COPD- and pneumonia-related outcomes were assessed over 13 months following influenza diagnosis. RESULTS: COPD-associated outcomes after diagnosis were significantly worse in patients with influenza (n = 7,087) vs. controls (n = 35,435) during the first month (exacerbation: 16.1 vs. 3.4%; outpatient visits: 57.1 vs. 35.2%; emergency department (ED) visits: 10.5 vs. 1.8%; and inpatient visits: 5.6 vs. 0.7%) and months 2-13 (exacerbation: 25.1 vs. 21.1%; outpatient visits: 86.1 vs. 85.8%; ED visits: 20.0 vs. 15.7%; and inpatient visits: 6.5 vs. 5.3%). COPD- and pneumonia-associated costs for months 1 and 2-13 were higher in patients with influenza. LIMITATIONS: The study was subject to a residual imbalance between cohorts despite propensity score matching. The use of diagnostic codes to select patients and identify complications could introduce inaccuracies in estimating events. CONCLUSIONS: HRU and costs were higher in COPD patients with influenza during the first month and over the entire year following infection. This suggests influenza has an impact on respiratory health in patients with COPD that lasts beyond the acute infection.

Dual-combination maintenance inhaler preferences in asthma and chronic obstructive pulmonary disease: A patient-centered benefit-risk assessment.

BACKGROUND: A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective. METHODS: Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD. RESULTS: For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoterol fumarate dihydrate (80 µg/4.5 µg) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 µg/5 µg) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 µg/2.5 µg) soft mist inhaler had the highest PrCP (42.3%). CONCLUSIONS: Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes.

Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD: A Post Hoc Analysis of the Informing the Pathway of COPD Treatment Trial.

BACKGROUND: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. RESEARCH QUESTION: Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? STUDY DESIGN AND METHODS: IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. RESULTS: The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [-1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. INTERPRETATION: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855.

Omalizumab Treatment Patterns Among Patients with Asthma in the US Medicare Population.

BACKGROUND: Asthma in older adults is associated with high rates of morbidity and mortality; similarly, asthma can be severe enough among younger adults to warrant disability benefits. Reasons for poor outcomes in both groups of patients may include discontinuation and lack of adherence to controller therapies. OBJECTIVE: To examine characteristics and treatment patterns of US Medicare patients initiating omalizumab for asthma, and factors associated with its discontinuation and adherence. METHODS: A retrospective claims database analysis of Medicare beneficiaries with asthma initiating omalizumab treatment was carried out. The primary outcomes were omalizumab discontinuation (gap in use ≥90 days) and adherence (proportion of days covered ≥0.8) over a 12-month follow-up. Multivariable regressions were used to examine factors associated with omalizumab discontinuation and adherence. RESULTS: Of the 3058 Medicare patients initiating omalizumab for asthma (mean age, 62.7 years), 36.9% discontinued omalizumab and 60.6% were adherent. Discontinuation rates were 32.7% and 42.8%, and adherence rates were 65.4% and 53.9%, for disabled and older Medicare patients, respectively. Patients aged 65 to 69 years and 70 to 74 years had significantly lower odds of discontinuation (odds ratios [95% CI], 0.66 [0.46-0.93] and 0.62 [0.43-0.89], respectively) and higher odds of adherence than did patients aged 80 years or older. Compared with patients receiving low-income subsidy, patients not receiving low-income subsidy had lower odds of discontinuation (0.66 [0.52-0.83]) and higher odds of adherence (1.52 [1.20-1.93]). Greater numbers of preindex evaluation and management physician visits and comorbid rhinitis were associated with lower odds of discontinuation and higher odds of adherence. CONCLUSIONS: More than 60% of Medicare patients with asthma continued and were adherent to omalizumab over a 12-month follow-up. Patient age, low-income subsidy status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation.

Bayesian inference of networks across multiple sample groups and data types.

In this article, we develop a graphical modeling framework for the inference of networks across multiple sample groups and data types. In medical studies, this setting arises whenever a set of subjects, which may be heterogeneous due to differing disease stage or subtype, is profiled across multiple platforms, such as metabolomics, proteomics, or transcriptomics data. Our proposed Bayesian hierarchical model first links the network structures within each platform using a Markov random field prior to relate edge selection across sample groups, and then links the network similarity parameters across platforms. This enables joint estimation in a flexible manner, as we make no assumptions on the directionality of influence across the data types or the extent of network similarity across the sample groups and platforms. In addition, our model formulation allows the number of variables and number of subjects to differ across the data types, and only requires that we have data for the same set of groups. We illustrate the proposed approach through both simulation studies and an application to gene expression levels and metabolite abundances on subjects with varying severity levels of chronic obstructive pulmonary disease. Bayesian inference; Chronic obstructive pulmonary disease (COPD); Data integration; Gaussian graphical model; Markov random field prior; Spike and slab prior.

The Hospital Readmissions Reduction Program and Readmissions for Chronic Obstructive Pulmonary Disease, 2006-2015.

Rationale: In October 2012, the initial phase of the Hospital Readmission Reduction Program imposed financial penalties on hospitals with higher-than-expected risk-adjusted 30-day readmission rates for Medicare beneficiaries with congestive heart failure, myocardial infarction, and pneumonia. We hypothesized that these penalties may also be associated with decreased readmissions for chronic obstructive pulmonary disease (COPD) in the general population before COPD became a target condition (October 2014).Objectives: To determine if implementation of the initial financial penalties for other conditions was associated with a decrease in hospital readmissions for COPD.Methods: We used population-level data to examine patients readmitted for any reason or for COPD within 30 days after an initial hospitalization for COPD. The data source was seven states in the State Inpatient Database. The preimplementation period included calendar years 2006 to 2012. The postimplementation period included 2013 to 2015. Using interrupted time series, the level change was examined, which reflected the difference between the expected and actual readmission rates in 2013. The difference in slopes between the pre- and postimplementation periods was also examined.Results: We identified 805,764 hospitalizations for COPD from 904 hospitals. Overall, 26% of patients had primary insurance other than Medicare. After the intervention, patients had lower rates of all-cause 30-day readmissions (level change, -0.93%; 95% confidence interval [CI], -1.44% to -0.43%; P = 0.004), which was driven by fewer early readmissions (0-7 d). The postimplementation slope became positive; the difference in slopes was 0.39% (95% CI, 0.28% to 0.50%; P < 0.001). Patients also had lower rates of COPD-related readmissions (level decrease, -0.52%; 95% CI, -0.93% to -0.12%; P = 0.02), which was due to decreases in both early and late (8-30 d) readmissions. The postimplementation slope was negative; the difference in slopes was -0.21% (95% CI, -0.35% to -0.07%; P = 0.009).Conclusions: In patients with COPD and any insurance status, there was an association between the initial phase of the Hospital Readmission Reduction Program and a decrease in both all-cause and COPD-related readmissions even before COPD became a target diagnosis. The large amount of money at risk to hospitals likely resulted in broad behavioral change. Future research is needed to test which levers can effectively reduce readmission rates for COPD.

Activity-related dyspnea in chronic obstructive pulmonary disease: physical and psychological consequences, unmet needs, and future directions.

Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD. In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety. Moreover, the anticipation of dyspnea itself can have a significant effect on patients' emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD. Dyspnea is, therefore, a key target for COPD treatments. Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients' increased inspiratory neural drive to breathe. However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea. Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes. Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention.

Cost-effectiveness of fractional exhaled nitric oxide (FeNO) measurement in predicting response to omalizumab in asthma.

Purpose: To use a modeled analysis to examine the cost-effectiveness of utilizing fractional exhaled nitric oxide (FeNO) as a biomarker to aid in the identification of omalizumab responders in patients with moderate-to-severe allergic asthma. Omalizumab is a biological drug used to treat asthma in adults and children 12 years and older. Patients and methods: We conducted a decision analysis in which two alternative strategies for predicting omalizumab response were assessed: 1) testing response via a 12-week trial of omalizumab and 2) using FeNO measurement to screen patients for likely omalizumab response prior to initiating a 12-week trial of omalizumab. In the standard of care arm, trial omalizumab responders continue on to receive 12 months of continuous omalizumab therapy. In the FeNO measurement predictor arm, patients with FeNO measurements >19.5 ppb are started on a trial of omalizumab. Trial omalizumab responders in this arm are then also tracked for 12 months of continuous omalizumab therapy. Results: Per-patient costs during the trial and initial treatment periods total $10,943 for FeNO + omalizumab and $13,703 for omalizumab only. The expected cost per responder during the trial period is $4,326 for FeNO + omalizumab and $7,786 for omalizumab only. Conclusion: Use of FeNO measurement to identify omalizumab responders decreases the expected per-patient cost by nearly 50% during the trial period and continues to show cost savings through the initial treatment period of 12 months. Our analysis may serve as a model for policy and clinical practice regarding the use of FeNO to determine omalizumab response and has widespread implications for health care payers, who may choose to require FeNO measurement and prespecify a minimum FeNO value to determine patient eligibility for omalizumab trial.

Radiation-Induced Lung Injury: Assessment and Management.

Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT) and manifests acutely as radiation pneumonitis and chronically as radiation pulmonary fibrosis. Because most patients with thoracic and breast malignancies are expected to undergo RT in their lifetime, many with curative intent, the population at risk is significant. Furthermore, indications for thoracic RT are expanding given the advent of stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) for early-stage lung cancer in nonsurgical candidates as well as oligometastatic pulmonary disease from any solid tumor. Fortunately, the incidence of serious pulmonary complications from RT has decreased secondary to advances in radiation delivery techniques. Understanding the temporal relationship between RT and injury as well as the patient, disease, and radiation factors that help distinguish RILI from other etiologies is necessary to prevent misdiagnosis. Although treatment of acute pneumonitis is dependent on clinical severity and typically responds completely to corticosteroids, accurately diagnosing and identifying patients who may progress to fibrosis is challenging. Current research advances include high-precision radiation techniques, an improved understanding of the molecular basis of RILI, the development of small and large animal models, and the identification of candidate drugs for prevention and treatment.

Trends in 30-day readmission rates after COPD hospitalization, 2006-2012.

BACKGROUND: Reduction in 30-day readmission rate after chronic obstructive pulmonary disease (COPD)-related hospitalization is a national objective. However, little is known about trends in readmission rates in recent years, particularly in priority populations defined by the Agency for Healthcare Research and Quality (AHRQ)(e.g., the elderly, women, racial/ethnic minorities, low-income and rural populations, and populations with chronic illnesses). METHODS: We conducted a retrospective cohort study using data from the State Inpatient Database of eight geographically-dispersed US states (Arkansas, California, Florida, Iowa, Nebraska, New York, Utah, and Washington) from 2006 through 2012. We identified all COPD-related hospitalizations by patients ?40 years old. The primary outcome was any-cause readmission within 30 days of discharge from the index hospitalization for COPD. RESULTS: From 2006 to 2012, a total of 845,465 hospitalizations at risk for 30-day readmissions were identified. Overall, 30-day readmission rate for COPD-related hospitalization decreased modestly from 20.0% in 2006 to 19.2% in 2012, an 0.8% absolute decrease (OR 0.991, 95%CI 0.989-0.995, Ptrend<0.001). This modest decline remained statistically significant after adjusting for patient demographics and comorbidities (adjusted OR 0.981, 95%CI 0.977-0.984, Ptrend<0.001). Similar to the overall population, the readmission rate over the 7-year period remained persistently high in most of AHRQ-defined priority populations. CONCLUSIONS: Our observations provide a benchmark for future investigation of the impact of Hospital Readmissions Reduction Program on readmissions after COPD hospitalization. Our findings encourage researchers and policymakers to develop effective strategies aimed at reducing readmissions among patients with COPD in an already-stressed healthcare system.

Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS: This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

A simplified score to quantify comorbidity in COPD.

IMPORTANCE: Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes. MATERIALS AND METHODS: Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS. RESULTS: Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624-0·7676), MMRC (0·7590-0·7644), 6MWD (0·7531-0·7560) and exacerbation risk (0·6831-0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341). CONCLUSIONS: Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD.

A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation.

BACKGROUND: A simple rule based on short-acting inhaled ß2-agonist (SABA) use could identify patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbations and signal the need for maintenance therapy change, similar to asthma "Rules of Two(®)". METHODS: Associations between SABA use, COPD exacerbations, and health care costs over 1 year were examined retrospectively using de-identified patient data from the Optum Research Database (ORD; N = 56,581) and the Impact National Benchmark Database (IMPACT™; N = 9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5 mg and 90 mcg albuterol equivalents, respectively. RESULTS: The GOLD initiative establishes ≥2 exacerbations/year as indicative of increased risk in COPD. We identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this frequency of exacerbations. In ORD, patients using ≥1.5 versus <1.5 SABA doses/day experienced significantly more exacerbations: 1.92 (95% confidence interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY). Above-threshold use was associated with higher average annual COPD-related costs (2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD, $32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853) for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for both nebulized and MDI SABA. IMPACT™ validated these findings. CONCLUSION: Patients with COPD using ≥1.5 SABA doses/day were at increased risk of exacerbations. Our results suggest a "Rule of 3-2": SABA use ≥3 times in 2 days should be considered a clinical marker for needing treatment reevaluation.

Asthma outcomes revisited.

PURPOSE OF REVIEW: Asthma outcomes constitute the cornerstone of asthma clinical research. Despite their known importance, it has been difficult for researchers to standardize these outcomes in large part because of the heterogeneity of the disease. This review seeks to provide an overview of recent recommendations for standardization of asthma outcomes in clinical trials, as well as discuss areas of future interest. RECENT FINDINGS: Several outcome measures have been recommended and are used in evaluating different interventions in asthma clinical trials. Such outcomes include lung function, asthma control measures, symptoms, exacerbations, quality of life, biomarkers, healthcare utilization and cost of care. More recently, recommendations for core measures, supplemental measures and future areas of interest for all future asthma clinical trials have been recommended by the Asthma Outcomes Workshop supported by the National Institute of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ) in the US. SUMMARY: Standardization of asthma outcomes allows the comparison of results across multiple studies and centers. The recommendations of the Asthma Outcomes Workshop constitute an excellent first step in standardizing the way in which asthma outcomes are assessed. The asthma research community is now charged with implementing these recommendations and expanding upon them.

Age-related differences in clinical outcomes for acute asthma in the United States, 2006-2008.

BACKGROUND: Little is known about the effect of age on acute asthma outcomes. OBJECTIVE: We sought to investigate age-related differences in the emergency department (ED) presentation and clinical outcomes for patients with acute asthma. METHODS: We analyzed the 2006-2008 Nationwide Emergency Department Sample, the largest, all-payer, US ED and inpatient database. ED visits for acute asthma were identified with a principal diagnosis of International Classification of Disease, ninth revision, Clinical Modification code 493.xx. Patients were divided into 3 age groups: children (<18 years), younger adults (18-54 years), and older adults (≥55 years). The outcome measures were in-hospital all-cause mortality, near-fatal asthma-related events (noninvasive or mechanical ventilation), hospital charges, admission rates, and hospital length of stay. RESULTS: There were an estimated 1,813,000 visits annually for acute asthma from approximately 4,700 EDs. The estimated overall annual number of in-hospital asthma-related deaths was 1,144 (0.06%); 101 died in the ED, and 1,043 died as inpatients. By age group, there were 37 asthma-related deaths per year in children, 204 in younger adults, and 903 in older adults. Compared with younger adults, older adults had higher mortality, had higher rates of near-fatal asthma-related events, had higher hospital charges, were more likely to be hospitalized, and had a longer hospital length of stay (P < .001 for all). After adjusting for comorbidities, older asthmatic patients had a 5-fold increased risk of overall mortality (adjusted odds ratio, 5.2; 95% CI, 4.0-6.9), compared with younger adults. CONCLUSIONS: Older adults with acute asthma have a substantial burden of morbidity and mortality. With the US population aging, there is an urgent need for targeted interventions for this high-risk population.

Clinical and economic burden of depression/anxiety in chronic obstructive pulmonary disease patients within a managed care population.

BACKGROUND: Anxiety and depression are common co-morbidities that can complicate the course of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate their impact on healthcare utilization and costs in a managed care COPD population. METHODS: Administrative claims data were used to conduct a retrospective cohort study of COPD patients ≥ 40 years of age, including those with co-morbid COPD-Depression (including anxiety). COPD-Depression patients were matched to COPD patients without depression (COPD-Only cohort) using propensity scores. Conditional logistic regression models assessed the 1-year risk of COPD exacerbations (i.e., emergency room [ER] visit/inpatient hospitalization) between cohorts. Differences in annual all-cause and COPD-related utilization/costs, along with 2-year costs, were also compared between the cohorts. RESULTS: There were 3,761 patients per cohort. Patients in the COPD-Depression cohort were 77% more likely to have a COPD-related hospitalization (odds ratio [OR] = 1.77, P < 0.001), 48% more likely to have an ER visit (OR = 1.48, P < 0.001), and 60% more likely to have hospitalization/ER visit (OR = 1.60, P < 0.001) compared to the COPD-Only cohort. Average annual all-cause medical cost per patient was $23,759 for COPD-Depression vs $17,765 for COPD-Only (P < 0.001) and total (medical plus pharmacy) cost was $28,961 vs $22,512 (P < 0.001), respectively; corresponding average annual COPD-related medical cost was $2,040 vs $1,392 (P < 0.001) and total cost was $3,185 vs $2,680 (P < 0.001). Similar trends were observed over the 2-year period. CONCLUSIONS: In the COPD population, patients with depression/anxiety have significantly higher risk of COPD exacerbations and annual all-cause and COPD-related costs than patients without these co-morbidities. These findings may have therapeutic implications and seem worthy of further exploration.

Clinical and economic burden of patients diagnosed with COPD with comorbid cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist, increasing the risk of hospitalization and mortality compared to either condition alone. The purpose of this study was to evaluate the impact of comorbid CVD on healthcare utilization and costs in a COPD population. METHODS: A retrospective cohort study of COPD patients CVD ± ≥40 years of age using administrative claims data was conducted. COPD-CVD patients were matched to COPD patients without CVD (COPD-Only cohort) using propensity scores. Multivariate analyses were conducted to assess the 1-year risk of COPD exacerbations (hospitalization and/or emergency room [ER] visits), along with differences in 1-year and 2-year all-cause and COPD-related utilization and costs (2008 USD) among COPD-CVD and COPD-Only cohorts. RESULTS: Each cohort included 4594 patients. Compared to COPD-Only cohort, the COPD-CVD cohort was almost 2 times more likely to require COPD-related hospitalization (odds ratio [OR], 1.95; p < 0.001), 47% more likely to have an ER visit (OR, 1.47; p < 0.001) and 62% more likely to require hospitalization and/or ER visit (OR, 1.62; p < 0.001). Average annual all-cause medical costs per patient were $22,755 for COPD-CVD vs $8036 for COPD-Only (p < 0.001), and total costs were $27,032 vs $11,506 (p < 0.001), respectively; corresponding average COPD-related annual medical costs were $1891 vs $1060 (p < 0.001) and total costs were $3295 vs $2379 (p < 0.001). CONCLUSIONS: COPD patients with CVD have significantly higher risk of COPD exacerbations and increased costs than COPD patients without CVD. This suggests a close association between COPD and CVD that warrants further exploration.