David H. Au

Risk for Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease

Context Many think we need more information about the safety of respiratory medications for chronic obstructive pulmonary disease (COPD). Contribution This large casecontrol study examined associations between medications and risk for death in veterans with newly diagnosed COPD. Inhaled corticosteroids were associated with decreased risk for death. Theophylline and ipratropium were associated with increased risk for respiratory and cardiovascular death, respectively. Caution Potential confounders, such as smoking status and disease severity, were not known. Associations may not reflect causal relationships. Implication Additional research about the safety of ipratropium, one of the most commonly prescribed medications for COPD, is needed. The Editors Chronic obstructive pulmonary disease (COPD) is associated with substantial burden in terms of prevalence of disease (1), death and disability risk (2, 3), and health care costs (4). Despite recent interest in examining long-term outcomes associated with medications in patients with COPD (5, 6), some issues are not easily addressed by using randomized clinical trials. From a pharmacovigilance perspective, relatively rare adverse eventssuch as death associated with medication usemay not be detected in the short term. The patients who receive a medication may not be similar to those participating in clinical trials (7, 8) and may be more vulnerable to such events. Thus, evidence of longer-term benefits and harms associated with medicationsparticularly in patients with COPD, who tend to be elderly and have multiple comorbid conditions (9)can be informed by research that relies on observational data. Potential safety concerns with medications used to manage COPD may be substantial. A recent meta-analysis (10) showed a nearly 2.5-fold increase in respiratory deaths among patients receiving long-acting -agonists compared with those receiving placebo. In the Lung Health Study (11), the group randomly assigned to ipratropium bromide had more than twice as many cardiovascular deaths as those receiving placebo. In addition, the U.S. Food and Drug Administration recently issued a notice regarding the potential for an increased risk for stroke associated with tiotropium use in patients with COPD (12). The extent to which these safety concerns exist and can be generalized to patients with COPD outside the context of clinical trials is unclear. Therefore, we sought to examine the association between medication use and risk for death, including respiratory and cardiovascular deaths, in a large population of patients with recently diagnosed COPD. Methods We conducted this nested casecontrol study in patients with recently diagnosed COPD by using national Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases, supplemented with data from the Centers for Medicare & Medicaid Services. Our sample comprised U.S. veterans who used the U.S. Veterans Health Administration health care system. The Hines Veterans Affairs Hospital, Hines, Illinois, institutional review board approved our research. Cohort Patients were eligible for inclusion if they received a diagnosis of COPD (International Classification of Diseases, 9th Revision [ICD-9], codes 491.x, 492.x, or 496) between 1 October 1999 and 30 September 2003 at 2 or more outpatient visits within 12 months or were admitted to the hospital with a primary diagnosis of COPD. Patients had to be 45 years of age or older when they received their first eligible diagnosis, have used Veterans Health Administration health care services for at least 1 year before their first COPD diagnosis, and have received respiratory medications. We excluded patients with a diagnosis of asthma. We followed patients from the date of their second eligible outpatient visit or their inpatient visit until death or 30 September 2004. Case Patients We identified all deaths that occurred during follow-up by using the Veterans Affairs Vital Status database, a combination of Veterans Affairs, Medicare, and Social Security Administration mortality data that captures approximately 98% of veteran deaths (13). Of these, 40% was randomly sampled and we attempted to determine cause of death. This sample was estimated to provide more than 80% power to detect odds ratios of 0.85 or lower or 1.15 or higher for each medication class. We ascertained cause of death by using National Death Index Plus data from the National Center for Health Statistics. We defined 4 groups of case patients on the basis of cause of death: respiratory, cardiovascular, respiratory or cardiovascular, and all-cause mortality. We defined respiratory as death due to a respiratory system disease (ICD-10 codes J00 to J99) and cardiovascular as death due to ischemic heart disease (ICD-10 codes I20 to I25), cardiomyopathy, cardiac arrest, or arrhythmias (ICD-10 codes I42 to I51). The index date for case patients was their death date. Control Participants Selecting more than 5 control participants per case patient can yield limited gains in efficiency; however, because we were assessing several medications simultaneously, we selected up to 10 control participants per case patient (14). We randomly selected control participants for each case patient from eligible patients who were alive at the time of the case event (15, 16). We matched control participants to case patients individually on the basis of sex, age category (45 to 54 years, 55 to 64 years, 65 to 74 years, 75 to 84 years, and 85 years of age), region of the country, and year of diagnosis. We assigned control participants the same index date as their matched case patients. Exposure We defined exposure to respiratory medications as having received medications in the 180 days preceding each patients index date. We identified medication exposure to inhaled corticosteroids, ipratropium, long-acting -agonists, theophylline, and short-acting -agonists. We defined primary exposure as any exposure in the 180-day period before the index date. We created mutually exclusive medication regimens on the basis of medication exposure. Exposure to short-acting -agonists was not considered as part of the regimen but was included as a covariate in the analysis. Covariates We identified covariates by using data from the year before diagnosis date until the index date. We used pharmacy data to identify medication use, including exposure to systemic steroids, antihypertensives, lipid-lowering medications, antiarrhythmics, and diabetes medications. We used inpatient and outpatient diagnoses to identify comorbid conditions. We measured health care utilization as the annual number of hospitalizations and outpatient physician visits. We identified COPD exacerbations during follow-up and whether they were inpatient or outpatient by using a previously described algorithm (17). Statistical Analysis We performed separate analyses for respiratory-specific, cardiovascular-specific, and all-cause mortality. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% CIs. We included the variables that we considered clinically important in each of the regression models. Specifically, we included measures of COPD-related severity in all of the models and included markers of cardiovascular disease in the models for cardiovascular and all-cause mortality. We included any remaining variables that changed OR estimates for respiratory medications by more than 10% in the final models (18). We assessed model fit by using the Bayesian information criterion and the Wald test of likelihood ratios and through examination of outlier effects with leverage and fit diagnostics (19). Adjusted odds ratios represented risk for events in patients receiving medication compared with those who had not received inhaled corticosteroids, ipratropium, long-acting -agonists, or theophylline in the previous 6 months. We performed all analyses with Stata/MP 10.0 for Windows (StataCorp, College Station, Texas). We conducted several sensitivity analyses to evaluate the robustness of our results. First, we restricted the comparison group to patients who were actively treated with a short-acting -agonist in the 180 days preceding the index date. Second, because veterans may use health care services outside the Veterans Health Administration system, we restricted the analysis to patients 65 years of age or older. We used Medicare health care utilization data on these patients to capture health care utilization outside of the Veterans Health Administration system. Third, we examined dose response by classifying those in the highest quartile of average daily dose into a high-dose group and the rest of those exposed into a low-dose group. Fourth, to observe the effects of ipratropium independent of short-acting -agonist exposure, we excluded patients who received a combination of ipratropium and short-acting -agonists in a single inhaler. Fifth, to address the imbalance in prevalence of chronic heart failure between case patients and control participants, we created analytic cohorts by matching on presence of chronic heart failure and repeated our analyses. Finally, we used the array approach to estimate the effect that unmeasured confounding could have had on point estimates of the association between medications and mortality (20). We varied the level of risk associated with the unmeasured confounder and the prevalence in the medication groups relative to the no-treatment groups to determine what level of differential exposure would change the conclusions from the primary analysis. We focused on current smoking rates and COPD severity because we considered these to be 2 of the most important and influential unmeasured confounders. We compared rates of smoking status and COPD severity across treatment groups by using data from a recently published study (21). Role of the Funding Source This research was funded by the U.S. Department of Veterans Affairs Health Services Research

Obesity and COPD: associated symptoms, health-related quality of life, and medication use.

Background: There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD. Methods: We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. Georges Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities. Results: The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV1 55.4% ±19.9% predicted, overweight: mean FEV1 50.0% ±20.4% predicted) than normal weight subjects (mean FEV1 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients. Conclusions: Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.

Lung Cancer and Hormone Replacement Therapy: Association in the Vitamins and Lifestyle Study

PURPOSE Lung cancer is the leading cause of cancer-related mortality among women. The role of hormone replacement therapy (HRT) in lung cancer development is unclear. PATIENTS AND METHODS We evaluated a prospective cohort of 36,588 peri- and postmenopausal women aged 50 to 76 years from Washington State recruited in 2000 to 2002 (Vitamins and Lifestyle [VITAL] Study). Lung cancer cases (n = 344) were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry during 6 years of follow-up. Hazard ratios (HRs) associated with use and duration of specific HRT formulations were calculated for total incident lung cancer, specific morphologies, and cancer by stage at diagnosis. RESULTS After adjusting for smoking, age, and other potential confounders, there was an increased risk of incident lung cancer associated with increasing duration of estrogen plus progestin (E+P) use (HR = 1.27 for E+P use 1 to 9 years, 95% CI, 0.91 to 1.78; and HR = 1.48 for E+P use > or = 10 years, 95% CI, 1.03 to 2.12; P for trend = .03). There was no association with duration of unopposed estrogen use. Duration of E+P use was associated with an advanced stage at diagnosis (P for trend = .03). CONCLUSION Use of E+P increased the risk of incident lung cancer in a duration-dependent manner, with an approximate 50% increased risk for use of 10 years or longer. These findings may be helpful for informing women of their risk of developing lung cancer and delineating important pathways involved in hormone metabolism and lung cancer.

Alcohol Screening Scores and Medication Nonadherence

Context Is alcohol misuse associated with medication nonadherence? Contribution This study of primary care patients attending 7 Veterans Affairs clinics found a graded, linear decrease in adherence to statins and hypertension medications with increasing levels of alcohol misuse. Caution Alcohol misuse was measured with a brief screening questionnaire that was mailed to patients. Adherence was measured by pharmacy refills. Implication Alcohol misuse may be associated with increased risk for medication nonadherence. The Editors Daily medications are the cornerstone of chronic disease management. Medications to treat hypertension, hyperlipidemia, and diabetespotent risk factors for cardiovascular diseaseare common and are often prescribed for asymptomatic patients to prevent future disease. However, nonadherence to medications is common (1) and is associated with poor outcomes, increased health care costs (2, 3), and death (4). Many studies have examined patient characteristics associated with nonadherence, but most identified risk factors for nonadherence are not modifiable. Alcohol misuse is common, has been associated with medication nonadherence, and is modifiable (57). However, research on alcohol misuse and medication adherence has been largely limited to patients with HIV (811) and a few studies of diabetes (3, 12, 13). One recent study found both a temporal and a doseresponse relationship between alcohol consumption and medication adherence (8) but used a lengthy interview measure of alcohol use that is not practical for busy clinical settings. Therefore, it remains unclear whether brief validated alcohol screening questionnaires used in clinical practice could identify patients at risk for nonadherence due to alcohol misuse. We examined whether primary care outpatient scores on a brief, scaled, alcohol screening questionnairethe Alcohol Use Disorder Identification TestConsumption (AUDIT-C)were associated with medication nonadherence. Specifically, we evaluated the association between increasing scores on the AUDIT-C (score range, 0 to 12) and adherence to oral medications commonly used for hypertension, hyperlipidemia, and diabetes. We hypothesized that higher AUDIT-C scores would be associated with an increased risk for medication nonadherence. Methods Participants and Setting We used data collected from the Ambulatory Care Quality Improvement Project (ACQUIP) cohort in this study (14). In brief, ACQUIP enrolled 36821 active patients from the general internal medicine clinics of 7 Veterans Affairs (VA) medical centers nationwide, including facilities in Seattle, Washington; West Los Angeles, California; Birmingham, Alabama; Little Rock, Arkansas; San Francisco, California; Richmond, Virginia; and White River Junction, Vermont. The ACQUIP initially surveyed all VA sites and selected these 7 sites (from 60 respondents) on the basis of geographic diversity; well-established systems for assigning patients to firms; and an experienced, interested investigator to lead the study. The ACQUIP was a randomized trial testing the effect of an audit and feedback quality-improvement intervention; there was no detectable effect of the intervention on primary outcomes, including alcohol misuse (14). Patients were eligible for ACQUIP if they had at least 1 visit to a primary care facility in the past year and had a primary care provider. The ACQUIP sent questionnaires (ACQUIP Health Checklist) at enrollment (1997 to 2000), and the institutional review board considered participant response to the survey to be consent for study participation. The survey assessed demographic characteristics, alcohol misuse, other health behaviors, and psychiatric and medical conditions. Patients who did not respond were mailed up to 3 additional surveys. The date the survey was received by the study team was considered the index date for all participants. Survey data were linked to electronic records, including pharmacy, diagnosis, and death records. Participants who died during follow-up were excluded. The institutional review board at each participating VA site approved ACQUIP, and the University of Washington Division of Human Subjects approved the secondary analyses that we present in this article. Pharmacy Data and Medication Cohorts Pharmacy data were retrieved electronically as part of the ACQUIP protocol from December 1995 to May 2000. Each prescription filled generated 1 record containing the drug name, the quantity and date dispensed, and the number of days supplied. These data are nearly identical to national VA pharmacy data (15), which have been used in several studies of medication adherence and pharmacoepidemiology (16, 17). We identified 3 nonexclusive cohorts of patients with increasing medication regimen complexity: a statin cohort, consisting of all patients prescribed a statin medication for hypercholesterolemia; an oral hypoglycemic cohort, with all patients who were prescribed either a sulfonylurea or metformin for blood glucose control; and a hypertension treatment cohort, consisting of all patients with self-reported hypertension who were prescribed at least 1 of 6 classes of antihypertensive drugs (-blockers, angiotensin-converting enzyme inhibitors, -blockers, calcium-channel blockers, thiazide-type diuretics, or nonthiazide diuretics) and a group consisting of other antihypertension medications usually used as fourth- or fifth-line agents (such as hydralazine). We considered patients medication users and included them in 1 of the cohorts if they received both 1 or more fills of the drug class within 2 years before the index date and 1 or more fills in the year after the index date. We used these criteria to minimize potential dropout bias by ensuring that patients were still engaged in care and obtaining medications from the VA. We excluded glitazones and angiotensin-receptor blockers from analyses because few patients were prescribed these medications, which were on a restricted formulary at the time of the study. In addition, we excluded patients in the oral hypoglycemic cohort if they had an active prescription for insulin other than neutral protamine Hagedorn, in order to remove patients who transitioned from oral medication to insulin during the study. Alcohol Misuse and AUDIT-C We assessed alcohol misuse with the AUDIT-C from the ACQUIP Health Checklist. The AUDIT-C assesses frequency and typical quantity of drinking during the past year, as well as the frequency of heavy episodic drinking (6 drinks per occasion) by using 3 questions (18). Each of the 3 questions is scored 0 to 4, for a total combined score of 0 to 12. The AUDIT-C is reliable (19) and has been validated as a screening test for the spectrum of alcohol misuse, including risky drinking and alcohol-use disorders on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (18, 20, 21). A score of 4 or more is considered positive for alcohol misuse in male VA patients, but the AUDIT-C score has also been shown to be a scaled measure of risk for alcohol-related symptoms (22) and medical complications often associated with alcohol misuse (2326). To provide adequate precision in estimates and allow comparison with previous analyses (23, 24), we grouped AUDIT-C scores into 5 categories: nondrinkers (score, 0); low-level alcohol use (score range, 1 to 3); and mild (score range, 4 to 5), moderate (score range, 6 to 7), and severe (score range, 8 to 12) alcohol misuse. Medication Adherence We created an individual measure of refill adherence, which was previously validated within the VA and ACQUIP, for each patient and medication class. This measure is similar to a medicationpossession ratio, and it accounts for overstocking and medication gaps, correlates better with physiologic outcomes when compared with previous measures, and is described in detail elsewhere (27). From this measure, we derived a proportion of days covered that reflected the number of days during the observation period that medication was available (17). We considered all medications within a medication type (statin, oral hypoglycemics, and antihypertensive medications) to be equivalent for purposes of adherence. We calculated adherence separately for 2 different periods: 90 days and 1 year starting from the index date. We assessed at 1 year because it is a traditional measurement of adherence (16, 17). We also assessed at 90 days because refill adherence for this period has been correlated with outcomes (27). On the basis of previous medication adherence literature (16, 17), we considered patients in all medication cohorts to be adherent if they had medication available for at least 80% of the observation period. In other words, for the 90-day observation period, nonadherent patients would not have medication available for at least 18 days; for the 1 year-period, they would be without medication for at least 73 days. When more than 1 medication was used (for example, for diabetes or hypertension), the proportions of days covered were averaged, and we considered patients to be adherent if they had at least 80% of the drug regimen for diabetes or hypertension available for the observation period. A person who met the definition of a user for 2 drug classes but only maintained complete fills of 1 drug with no fills of the other drug therefore would have an average adherence of 0.5 and would be considered nonadherent to the overall regimen. Covariates Race was based on a combination of self-report from the ACQUIP Health Checklist and the electronic record. We determined sex, education, and marital status from the ACQUIP Health Checklist. We calculated a drug count from the number of oral drugs that patients obtained during the year before the index date to adjust for total medication regimen complexity. We classified smoking status as current, former, or never. We assessed depression with the Mental Health Inventory (score range, 5 to 30); scores gre

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement highlighting research areas that will have the greatest impact on patient-centred outcomes in COPD http://ow.ly/LXW2J

A refill adherence algorithm for multiple short intervals to estimate refill compliance (ReComp)

Background: There are many measures of refill adherence available, but few have been designed or validated for use with repeated measures designs and short observation periods. Objective: To design a refill-based adherence algorithm suitable for short observation periods, and compare it to 2 reference measures. Methods: A single composite algorithm incorporating information on both medication gaps and oversupply was created. Electronic Veterans Affairs pharmacy data, clinical data, and laboratory data from routine clinical care were used to compare the new measure, ReComp, with standard reference measures of medication gaps (MEDOUT) and adherence or oversupply (MEDSUM) in 3 different repeated measures medication adherence-response analyses. These analyses examined the change in low density lipoprotein (LDL) with simvastatin use, blood pressure with antihypertensive use, and heart rate with β-blocker use for 30- and 90-day intervals. Measures were compared by regression based correlations (R2 values) and graphical comparisons of average medication adherence-response curves. Results: In each analysis, ReComp yielded a significantly higher R2 value and more expected adherence-response curve regardless of the length of the observation interval. For the 30-day intervals, the highest correlations were observed in the LDL-simvastatin analysis (ReComp R2 = 0.231; [95% CI, 0.222–0.239]; MEDSUM R2 = 0.054; [95% CI, 0.049–0.059]; MEDOUT R2 = 0.053; [95% CI, 0.048–0.058]). Conclusions: ReComp is better suited to shorter observation intervals with repeated measures than previously used measures.

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

BackgroundAdministrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.MethodsSequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria.Results4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).ConclusionCommonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.

Cardiovascular Events Associated With Ipratropium Bromide in COPD

BACKGROUND Studies have suggested an increased risk of cardiovascular morbidity and mortality associated with the use of ipratropium bromide. We sought to examine the association between ipratropium bromide use and the risk of cardiovascular events (CVEs). METHODS We performed a cohort study of 82,717 US veterans with a new diagnosis of COPD between 1999 and 2002. Subjects were followed until they had their first hospitalization for a CVE (acute coronary syndrome, heart failure, or cardiac dysrhythmia), they died, or the end of the study period (September 30, 2004). Cumulative anticholinergic exposure was calculated as the number of 30-day equivalents (ipratropium bromide) within the past year. We used Cox regression models with time-dependent covariates to estimate the risk of CVE associated with anticholinergic exposure and to adjust for potential confounders, including markers of COPD severity and cardiovascular risk. RESULTS We identified 6,234 CVEs (44% heart failure, 28% acute coronary syndrome, 28% dysrhythmia). Compared with subjects not exposed to anticholinergics within the past year, any exposure to anticholinergics within the past 6 months was associated with an increased risk of CVE (hazard ratio [95% CI] for< or =four and>four 30-day equivalents: 1.40 [1.30-1.51] and 1.23 [1.13-1.36], respectively). Among subjects who received anticholinergics more than 6 months prior, there did not appear to be elevated risk of a CVE. CONCLUSIONS We found an increased risk of CVEs associated with the use of ipratropium bromide within the past 6 months. These findings are consistent with previous concerns raised about the cardiovascular safety of ipratropium bromide.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement: which types of research will have the greatest future impact on patient-centred outcomes in COPD? http://ow.ly/I54Hb

Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension

Background β-Blocker therapy has been shown to improve survival among patients with ischaemic heart disease (IHD) and congestive heart failure (CHF) and is underused among patients with chronic obstructive pulmonary disease (COPD). Evidence regarding the optimal use of β-blocker therapy during an acute exacerbation of COPD is particularly weak. Methods We conducted a retrospective cohort study of patients aged ≥40 years with IHD, CHF or hypertension who were hospitalised for an acute exacerbation of COPD from 1 January 2006 to 1 December 2007 at 404 acute care hospitals throughout the USA. We examined the association between β-blocker therapy and in-hospital mortality, initiation of mechanical ventilation after day 2 of hospitalisation, 30-day all-cause readmission and length of stay. Results Of 35 082 patients who met the inclusion criteria, 29% were treated with β blockers in the first two hospital days, including 22% with β1-selective and 7% with non-selective β blockers. In a propensity-matched analysis, there was no association between β-blocker therapy and in-hospital mortality (OR 0.88, 95% CI 0.71 to 1.09), 30-day readmission (OR 0.96, 95% CI 0.89 to 1.03) or late mechanical ventilation (OR 0.98, 95% CI 0.77 to 1.24). However, when compared with β1 selective β blockers, receipt of non-selective β blockers was associated with an increased risk of 30-day readmission (OR 1.25, 95% CI 1.08 to 1.44). Conclusions Among patients with IHD, CHF or hypertension, continuing β1-selective β blockers during hospitalisation for COPD appears to be safe. Until additional evidence becomes available, β1-selective β blockers may be superior to treatment with a non-selective β blocker.