Towards A Revolution In COPD Health Research Articles

Medications for chronic obstructive pulmonary disease: a historical non-interventional cohort study with validation against RCT results.

Chronic obstructive pulmonary disease treatment is informed by randomised controlled trial results, but it is unclear if these findings apply to people excluded from these trials. We used data from the TORCH (TOwards a Revolution in COPD Health) randomised controlled trial to validate non-interventional methods for assessing the clinical effectiveness of chronic obstructive pulmonary disease treatment in the UK Clinical Practice Research Datalink, before applying these methods to the analysis of people who would have been excluded from TORCH. To validate the use of non-interventional Clinical Practice Research Datalink data and methods for estimating chronic obstructive pulmonary disease treatment effects against trial results, and, using validated methods, to determine treatment effects in people who would have been excluded from the TORCH trial. A historical non-interventional cohort design, including validation against randomised controlled trial results. The UK Clinical Practice Research Datalink. People aged ≥ 18 years with chronic obstructive pulmonary disease registered in Clinical Practice Research Datalink GOLD between January 2000 and January 2017. For objective 1, we prepared a cohort that was analogous to the TORCH trial cohort by applying TORCH trial inclusion/exclusion criteria followed by individual matching to TORCH trial participants. For objectives 2 and 3, we prepared cohorts that were analogous to the TORCH trial that, nevertheless, would not have been eligible for the TORCH trial because of age, asthma, comorbidity or mild disease. The long-acting beta-2 agonist and inhaled corticosteroid combination product Seretide (GlaxoSmithKline plc) [i.e. fluticasone propionate plus salmeterol (FP-SAL)] compared with (1) no FP-SAL exposure or (2) exposure to salmeterol (i.e. the long-acting beta-2 agonist) only. Exacerbations, mortality, pneumonia and time to treatment change. For objective 1, the exacerbation rate ratio was comparable to that in the TORCH trial for FP-SAL compared with salmeterol (0.85, 95% confidence interval 0.74 to 0.97, vs. TORCH trial 0.88, 95% confidence interval 0.81 to 0.95), but not for FP-SAL compared with no FP-SAL (1.30, 95% confidence interval 1.19 to 1.42, vs. TORCH trial 0.75, 95% confidence interval 0.69 to 0.81). Active comparator results were also consistent with the TORCH trial for mortality (hazard ratio 0.93, 95% confidence interval 0.65 to 1.32, vs. TORCH trial hazard ratio 0.93, 95% confidence interval 0.77 to 1.13) and pneumonia (risk ratio 1.39, 95% confidence interval 1.04 to 1.87, vs. TORCH trial risk ratio 1.47, 95% confidence interval 1.25 to 1.73). For objectives 2 and 3, active comparator results were consistent with the TORCH trial for exacerbations, with the exception of people with milder chronic obstructive pulmonary disease, in whom we observed a stronger protective association (risk ratio 0.56, 95% confidence interval 0.46 to 0.70, vs. TORCH trial risk ratio 0.85, 95% confidence interval 0.74 to 0.97). For the analysis of mortality, we saw a lack of association with being prescribed FP-SAL (vs. being prescribed salmeterol), with the exception of those with prior asthma, for whom we observed an increase in mortality (hazard ratio 1.49, 95% confidence interval 1.21 to 1.85, vs. TORCH trial-analogous HR 0.93, 95% confidence interval 0.64 to 1.32). Routinely collected electronic health record data can be used to successfully measure chronic obstructive pulmonary disease treatment effects when comparing two treatments, but not for comparisons between active treatment and no treatment. Analyses involving patients who would have been excluded from trials mostly suggests that treatment effects for FP-SAL are similar to trial effects, although further work is needed to characterise a small increased risk of death in those with concomitant asthma. Some of our analyses had small numbers. The differences in treatment effects that we found should be investigated further in other data sets. Currently recommended chronic obstructive pulmonary disease inhaled combination therapy (other than FP-SAL) should also be investigated using these methods. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 51. See the NIHR Journals Library website for further project information.

Re-evaluation of combination therapy in chronic obstructive pulmonary disease (COPD).

Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH). Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing). Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p = 0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p = 0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p = 0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001. In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful.

Observational Studies of Inhaled Corticosteroid Effectiveness in COPD: Lessons Learned

Randomized controlled trials at times investigate findings suggested by observational studies. For example, the Towards a Revolution in COPD Health (TORCH) trial, which did not show a mortality reduction with inhaled corticosteroids (ICS) in COPD, was motivated by some observational studies that suggested considerable reductions in mortality with these drugs. Reasons for these discrepancies are unclear. The literature was searched to identify all observational studies, including cohort and case-control studies, investigating the effectiveness of ICS on major outcomes in patients with COPD; these outcomes included death and hospitalization for COPD. A total of 21 studies were identified. Nine studies were affected by immortal time bias, five by immeasurable time bias, and seven by the "asthma factor" bias; some studies were affected by more than one bias. These studies found important reductions in the rates of major COPD outcomes with ICS use, with pooled rate ratios of 0.71 (95%CI, 0.67-0.76), 0.76 (95%CI, 0.70-0.83), and 0.79 (95%CI, 0.73-0.87), respectively, for the three sources of bias. In contrast, the five studies unaffected by these major biases did not find an association (pooled rate ratio, 1.02 [95%CI, 0.88-1.17]). Observational studies are important to provide evidence from real-world data on medication effects. However, appropriate study design and analysis are essential to avoid biases and ensure randomized trials with greater chances of success. The observational studies suggesting potential beneficial effects of nonrespiratory drugs to treat COPD, such as statins and beta-blockers, will also need careful review before long and expensive randomized trials are conducted.

Real-world effects of medications for chronic obstructive pulmonary disease: protocol for a UK population-based non-interventional cohort study with validation against randomised trial results

IntroductionChronic obstructive pulmonary disease (COPD) is a progressive disease affecting 3 million people in the UK, in which patients exhibit airflow obstruction that is not fully reversible. COPD treatment guidelines...

Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy

ABSTRACTClinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial — N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.

External Validation of Health Economic Decision Models for Chronic Obstructive Pulmonary Disease (COPD): Report of the Third COPD Modeling Meeting.

To validate outcomes of presently available chronic obstructive pulmonary disease (COPD) cost-effectiveness models against results of two large COPD trials-the 3-year TOwards a Revolution in COPD Health (TORCH) trial and the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial. Participating COPD modeling groups simulated the outcomes for the placebo-treated groups of the TORCH and UPLIFT trials using baseline characteristics of the trial populations as input. Groups then simulated treatment effectiveness by using relative reductions in annual decline in lung function and exacerbation frequency observed in the most intensively treated group compared with placebo as input for the models. Main outcomes were (change in) total/severe exacerbations and mortality. Furthermore, the absolute differences in total exacerbations and quality-adjusted life-years (QALYs) were used to approximate the cost per exacerbation avoided and the cost per QALY gained. Of the six participating models, three models reported higher total exacerbation rates than observed in the TORCH trial (1.13/patient-year) (models: 1.22-1.48). Four models reported higher rates than observed in the UPLIFT trial (0.85/patient-year) (models: 1.13-1.52). Two models reported higher mortality rates than in the TORCH trial (15.2%) (models: 20.0% and 30.6%) and the UPLIFT trial (16.3%) (models: 24.8% and 36.0%), whereas one model reported lower rates (9.8% and 12.1%, respectively). Simulation of treatment effectiveness showed that the absolute reduction in total exacerbations, the gain in QALYs, and the cost-effectiveness ratios did not differ from the trials, except for one model. Although most of the participating COPD cost-effectiveness models reported higher total exacerbation rates than observed in the trials, estimates of the absolute treatment effect and cost-effectiveness ratios do not seem different from the trials in most models.

Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) Model Using Data from ECLIPSE: Internal Validation of a Linked-Equations Cohort Model.

The recent joint International Society for Pharmacoeconomics and Outcomes Research / Society for Medical Decision Making Modeling Good Research Practices Task Force emphasized the importance of conceptualizing and validating models. We report a new model of chronic obstructive pulmonary disease (COPD) (part of the Galaxy project) founded on a conceptual model, implemented using a novel linked-equation approach, and internally validated. An expert panel developed a conceptual model including causal relationships between disease attributes, progression, and final outcomes. Risk equations describing these relationships were estimated using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, with costs estimated from the TOwards a Revolution in COPD Health (TORCH) study. Implementation as a linked-equation model enabled direct estimation of health service costs and quality-adjusted life years (QALYs) for COPD patients over their lifetimes. Internal validation compared 3 years of predicted cohort experience with ECLIPSE results. At 3 years, the Galaxy COPD model predictions of annual exacerbation rate and annual decline in forced expiratory volume in 1 second fell within the ECLIPSE data confidence limits, although 3-year overall survival was outside the observed confidence limits. Projections of the risk equations over time permitted extrapolation to patient lifetimes. Averaging the predicted cost/QALY outcomes for the different patients within the ECLIPSE cohort gives an estimated lifetime cost of £25,214 (undiscounted)/£20,318 (discounted) and lifetime QALYs of 6.45 (undiscounted/5.24 [discounted]) per ECLIPSE patient. A new form of model for COPD was conceptualized, implemented, and internally validated, based on a series of linked equations using epidemiological data (ECLIPSE) and cost data (TORCH). This Galaxy model predicts COPD outcomes from treatment effects on disease attributes such as lung function, exacerbations, symptoms, or exercise capacity; further external validation is required.

Cause-specific mortality adjudication in the UPLIFT® COPD trial: Findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

Are COPD patients with pneumonia who are taking inhaled corticosteroids at higher risk of dying?

In 2007, Calverley et al . [1] reported the results of the TORCH (Towards a Revolution in Chronic Obstructive Pulmonary Disease Health) study, which showed that combination of salmeterol (a long-acting β-agonist (LABA)) plus fluticasone propionate (an inhaled corticosteroid (ICS)) had a trend toward a lower all-cause mortality rate in patients with chronic obstructive pulmonary disease (COPD) compared with the placebo group, with a hazard ratio of 0.825 (95% CI 0.68–1.002; p = 0.052). Despite the beneficial effects of ICS therapy in COPD patients, the results raised a possible safety issue regarding higher rate of community-acquired pneumonia (CAP) in the ICS groups. The probability of having pneumonia was higher among subjects receiving medications containing ICS (19.6% for ICS plus LABA and 18.3% for ICS alone) compared with the placebo group (12.3%; p<0.001) [1]. This association between ICS and pneumonia in COPD patients has also been seen in other studies: one study that examined the potential benefit of ICS and LABAs in reducing COPD mortality [1], and another comparing COPD exacerbation rates between patients receiving either salmeterol or the combination with a LABA [2, 3]. A follow-up evaluation of the TORCH study identified several risk factors associated with pneumonia, including age ≥55 yrs, forced expiratory volume in 1 s <50% predicted, COPD exacerbation in the year prior to the study, worse Medical Research Council dyspnoea score and body mass index <25 kg·m−2. However, mortality rate due to pneumonia was not increased among subjects treated with ICS plus LABA, but the same could not be concluded for ICS monotherapy [4]. Therefore, it was suggested that ICS use increases the risk of CAP in COPD patients; however, the CAP severity event may be milder, and it is possible that these …

Arguments Against Inhaled Glucocorticoids in COPD by Phenotype Instead of by Severity

Before entering into the debate created by the title proposed by the Editorial Committee of Archivos de Bronconeumologia, I believe it is essential to establish three previous considerations. The first is in reference to the use of glucocorticoids in stable COPD. Currently, and after the results of the Towards a Revolution in COPD Health (TORCH)1 assay, it is difficult to recommend their continuous use in an isolated manner (monotherapy) without associating at least one long-acting beta-agonist bronchodilator, either separately or combined in the same device. From the perspective of therapeutic efficacy as well as from that of safety, the TORCH assay shows that the combination of an inhaled glucocorticoid with a long-acting beta-agonist is always better than the individual use of these two components. The second consideration is the term “phenotype”, understood as those structural and functional characteristics observed in an organism that aremodulated by interaction with the genotype and setting.2 The third and last is the word “severity”, which in stable COPD should be contextualized within the framework of the clinical data and the spirometric anomalies. Having set these three premises, I will center the debate within the context of the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD). Starting with the first version of the Executive Summary in 20013 and later in the second from 2007,4 the GOLD proposal has coherently defended a series of suggestions related with the management and treatment of stable COPD. These are based on the principle that the clinical approach and pharmacologic treatment of COPD (aside from exacerbations) are characterized by a staggered increase of the medication depending on the severity of the disease and its response to the individual therapeutic possibilities of each patient. And it indicates that the severity of the disease is determined by the relevance of the symp-

Predicting EQ-5D Values Using the SGRQ

Objectives The purpose of this study was to develop and validate an algorithm that predicts EQ-5D utility from the St. George's Respiratory Questionnaire (SGRQ) in subjects with chronic obstructive pulmonary disease and to examine the effect of using this algorithm in predicting quality-adjusted life-years (QALYs). Methods In the TORCH (Towards a Revolution in COPD Health) trial, the SGRQ and EQ-5D were administered at baseline and every 24 weeks for 3 years. To map EQ-5D utility from the SGRQ, ordinary least squares (OLS), generalized linear models (GLMs) and two-part models were used. Algorithms were developed in a fitting sample and used to predict utility scores in a validation sample and selected based on root-mean-square error (RMSE). QALYs were estimated from the algorithm and compared to QALYs derived from EQ-5D utility scores collected in the trial. Results A simple OLS algorithm was found to perform as well as algorithms developed using more complex modeling structures. The resulting model was (RMSE 0.1723): EQ-5D = 0.9617 − 0.0013 × SGRQ total − 0.0001 × SGRQ total 2 + 0.0231 × male. Ordering of treatments by QALY gain was dependent on the method of utility estimation. Conclusion A mapping algorithm can be used to predict EQ-5D utility scores from the SGRQ and may be useful in some situations; however, for use in a health technology assessment (HTA) submission in which precision of estimation is important, it is in the interests of both the manufacturer and the HTA body that utility scores be directly derived from the clinical trial population.

Prevalence of osteoporosis and osteopenia in advanced chronic obstructive pulmonary disease patients

Background:Reduction of bone mineral density (BMD) is a known and established phenomenon in chronic obstructive pulmonary disease (COPD). However, there have been no data regarding osteoporosis/osteopenia in COPD patients in India.Aim:To look for the degree and frequency of osteoporosis/osteopenia in our OPD patients being diagnosed as COPD.Materials and Methods:Thirty-seven randomly selected patients with COPD were assessed for BMD with commercially available ultrasound bone densitometer (HOLOGIC SAHARA) in a pulmonary OPD. Some cofactors for reduced BMD were also noted.Results:Out of the 37 COPD (all belonging to the GOLD III/IV category) patients studied, the BMD was found to be normal in 10 (27%) patients, while 27 (73%) patients were found to have osteopenia/osteoporosis [19 (51.35%) and 8 (21.62%) patients having osteopenia and osteoporosis, respectively].Conclusion:Frequency of osteoporosis and osteopenia was found to be very high (73%) in our population of advanced COPD. The data suggest a need for further in-depth study regarding the issue.

Bias due to withdrawal in long‐term randomised trials in COPD: Evidence from the TORCH study

Randomised controlled trials (RCTs) are considered the least biased method for evaluating drug efficacy and several large long-term RCTs in chronic obstructive pulmonary disease have been published. These usually include drugs with symptomatic benefits and have significant withdrawal rates. We aimed at examining bias due to differential withdrawal in the Towards a Revolution in COPD Health (TORCH) trial. We did an observational study nested in the TORCH trial, a placebo-controlled trial of salmeterol/fluticasone propionate combination (SFC) therapy in chronic obstructive pulmonary disease. We included 3057 patients randomly allocated to placebo or SFC in the analyses. We examined rates of withdrawal from the study and analysed change in effect parameters over time and in relation to withdrawal, as well as medication uptake after withdrawal. There was differential withdrawal with a significantly higher withdrawal rate from the group allocated to placebo than to SFC, 44% compared with 34%. Regardless of treatment group, withdrawal was associated with worse baseline lung function and more frequent exacerbations, leading to selection of a study population in better health than those originally recruited. As a result, annualized exacerbation rates in the first 6 months of the study compared with the last 6 months of the study decreased from 6.8 to 0.9 in the placebo group and from 3.0 to 0.8 in the SFC group. Also, use of medications under test in the study was frequent in patients after withdrawal. Significant bias may occur in long-term RCTs of registered medications with symptomatic benefits as a result of differential withdrawal.

Mortality in COPD: Causes, Risk Factors, and Prevention

ABSTRACTChronic obstructive pulmonary disease (COPD) is a leading and increasing cause of death, the extent of which is underestimated as a consequence of underdiagnosis and underreporting on death certificates. Data from large trials, such as the Lung Health Study, Towards a Revolution in COPD Health (TORCH), Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT), European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP), and Inhaled Steroids in Obstructive Lung Disease (ISOLDE), have shown that the causes of death in patients with mild COPD are predominantly cancer and cardiovascular disease, but as COPD severity increases, deaths due to non-malignant respiratory disease are increasingly common. In practice, mortality of patients with COPD can be predicted by a variety of measures including: forced expiratory volume in one second (FEV1), the ratio of inspiratory and total lung capacities, exercise capacity, dyspnea scores, and composite indices such as the body-mass index (B), degree of airflow obstruction (O), degree of functional dyspnea (D), and exercise capacity (E) (BODE) index. Smoking cessation improves survival in COPD patients, and in select patients with advanced disease, oxygen therapy, lung volume reduction surgery, or lung transplantation may also improve survival.

Cardiovascular events in patients with COPD: TORCH Study results

BackgroundPrevious studies have suggested that long-term use of β agonists to treat chronic obstructive pulmonary disease (COPD) may increase the risk of cardiovascular adverse events. In this post hoc analysis,...

Transportability of Comparative Effectiveness and Cost-Effectiveness between Countries

the results for registration in more than one country. At the same time, this design poses a number of challenges for interpreting the resulting cost-effectiveness ratio(s). One of these challenges is whether the data required for cost-effectiveness analysis—and thus the cost-effectiveness recommendations—can be assumed to be equivalent across the different countries. In this article, a brief overview of the literature on economic analysis of multinational studies is presented. The first section relates to the background on the transferability of economic data and the second section discusses the results of a consensus conference on economic analysis of multinational trials. The third section considers the two main statistical approaches that have been advocated for handling the analysis of multinational data—fixed effect and random effect modeling methods—plus a third approach that has only recently been employed in the literature based on modeling the components of the costeffectiveness calculus. This approach is then illustrated using the results of the recently published cost-effectiveness analysis of the TOwards a Revolution in COPD Health (TORCH) trial [1]. A final section offers some conclusions for the use of such methods in comparative effectiveness and cost-effectiveness studies.

Accuracy of Death Certificates in COPD: Analysis from the TORCH Trial

ABSTRACTThe Towards a Revolution in COPD Health (TORCH) trial was an international clinical trial of chronic obstructive pulmonary disease (COPD) patients where cause of death was assigned by an independent committee. Comparison of death certificate data and adjudicated cause of death allows a unique opportunity to determine death certificate accuracy and frequency of COPD listing on death certificates of COPD patients. In this analysis, the authors determine the concordance between adjudicated cause of death and primary and secondary cause of death from death certificates. In 317 (80%) of informative deaths, the primary or secondary cause of death from certificates agreed with adjudicated cause of death. Only 229 (58%) of death certificates in these COPD patients listed COPD on the certificate. COPD was not listed on the death certificate in 21% of deaths adjudicated to be caused by COPD exacerbation. Compared with pulmonary causes, the listing of COPD on certificates occurred with less frequency than cardiovascular, cancer and other categories of death. The combined primary and secondary listing on death certificates has good concordance with actual cause of death. COPD is under-reported on death certificates, and this under-reporting is more frequent when the primary cause of death is not pulmonary.

Steroids in COPD: still up in the air?

Inhaled corticosteroids (ICS) have had a wild and controversial rollercoaster ride in chronic obstructive pulmonary disease (COPD). With the success of ICS in asthma and with the advent of the Dutch Hypothesis, suggesting that asthma and COPD had a similar pathogenic origin, there was great hope that ICS would be the saviour for millions of patients suffering from COPD, by palliating symptoms and changing its natural history. Based on this promise, by the mid 1980s, clinicians were routinely recommending ICS therapy to their patients, even though there was an absence of compelling grade A evidence from large randomised controlled trials (RCTs) demonstrating efficacy 1. By the late 1990s, the promise was shattered by the publication of several seminal RCTs that clearly showed that ICS did not modify the rate of decline in forced expiratory volume in 1 s (FEV1) and had only a modest effect on symptoms 2–4. These data re-inforced the notion that COPD was a steroid-resistant state and many leading experts in the field concluded that ICS had no role in COPD, except during exacerbations 5. Ostensibly, ICS were dead and buried. However, the new millennium brought new hope for ICS. Proponents argued that while ICS may not alter the rate of decline in FEV1, it improved patient based outcomes including survival. This optimism was fuelled by several large observational studies and meta-analyses 6–9 that demonstrated a distinct survival benefit for patients who were prescribed ICS. This enthusiasm, however, was dashed in 2007 by the publication of the long-awaited TORCH (TOwards a Revolution in COPD Health) Study, which failed to show an unequivocal survival advantage for patients assigned to a steroid-containing treatment …

Update in Pulmonary and Critical Care Medicine

This Update in Pulmonary and Critical Care Medicine features 12 articles published in 2009. Topics include chronic obstructive pulmonary disease, asthma, pneumonia, glucose control and mortality, e...

Prevalence and Progression of Osteoporosis in Patients With COPD: Results From the Towards a Revolution in COPD Health Study

Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study.A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded.At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and -3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%).Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo.ClinicalTrials.gov Identifier: NTC00268216.