Primary Care COPD Patients Compared with Large Pharmaceutically-Sponsored COPD Studies : An UNLOCK Validation Study
TL;DR: Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations, as hitherto unknown GOLD I exacerbation characteristics are revealed.
Abstract: Background: Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS). There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care. Objective: We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials. Methods: Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS. In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria. Results: Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p = 1 and >= 2 exacerbations, although results were not statistically significant. Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had >= 1 exacerbations per year and 12% had >= 2 exacerbations per year. The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT). Conclusion: Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations. More research is needed to determine the effect of pharmacological treatment in mild to moderate patients. We encourage future guideline makers to involve primary care populations in their recommendations.
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TL;DR: The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination of inhaled corticosteroids and long-acting beta agonists.
Abstract: Previous studies have found suboptimal control of symptom burden to be widespread among patients with asthma and chronic obstructive pulmonary disease (COPD). The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination (FDC) of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). SPRINT included 1101 patients with asthma and 560 with COPD; all were receiving treatment with an FDC of ICS/LABA, delivered via various inhalers. Data were obtained over a 3-month period, during a single routine physician’s office visit. Asthma control was defined as Asthma Control Test (ACT) score >19. COPD symptom burden was assessed by COPD Assessment Test (CAT), with a CAT score 19) and 16% of patients with COPD had low symptom burden (CAT score <10).
25 citations
TL;DR: An ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy and LAMA monotherapy versus tiotropium, with a focus on the relative merits of the study design is described.
Abstract: Long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.
21 citations
TL;DR: Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD, and in women, current smoking is of specific importance for this phenotype.
Abstract: Background: Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD. The aim o ...
21 citations
Cites background from "Primary Care COPD Patients Compared..."
...Each respiratory unit was asked to consecutively enroll a maximum of ten patients with GOLD grade III COPD and five patients with GOLD grade IV COPD(1) during the period from May 12, 2011 to March 28, 2012, approximately matching the distribution of severe and very severe COPD in the general population.(19,20) The only exclusion criterion was an inability to complete the study on language grounds....
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TL;DR: Important shortcomings and challenges for the care of COPD patients in the Netherlands are revealed, emphasizing the need for detailed patient characterization and more individualized treatment, independent of the healthcare setting.
20 citations
TL;DR: Electronic medical record algorithms can accurately identify patients with chronic obstructive pulmonary disease in primary care records and suggest opportunities for broader, informative studies of COPD in wider populations, according to a retrospective chart abstraction study.
Abstract: Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care. Our objective was to develop electronic medical record algorithms that can accurately identify patients with obstructive pulmonary disease. A retrospective chart abstraction study was conducted on data from the Electronic Medical Record Administrative data Linked Database (EMRALD®) housed at the Institute for Clinical Evaluative Sciences. Abstracted charts provided the reference standard based on available physician-diagnoses, chronic obstructive pulmonary disease-specific medications, smoking history and pulmonary function testing. Chronic obstructive pulmonary disease electronic medical record algorithms using combinations of terminology in the cumulative patient profile (CPP; problem list/past medical history), physician billing codes (chronic bronchitis/emphysema/other chronic obstructive pulmonary disease), and prescriptions, were tested against the reference standard. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) were calculated. There were 364 patients with chronic obstructive pulmonary disease identified in a 5889 randomly sampled cohort aged ≥ 35 years (prevalence = 6.2%). The electronic medical record algorithm consisting of ≥ 3 physician billing codes for chronic obstructive pulmonary disease per year; documentation in the CPP; tiotropium prescription; or ipratropium (or its formulations) prescription and a chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95% CI:72.2–81.2), specificity of 99.7% (99.5–99.8), PPV of 93.6% (90.3–96.1), and NPV of 98.5% (98.1–98.8). Electronic medical record algorithms can accurately identify patients with chronic obstructive pulmonary disease in primary care records. They can be used to enable further studies in practice patterns and chronic obstructive pulmonary disease management in primary care. Researchers develop an algorithm that can accurately search through electronic health records to find patients with chronic lung disease. Mining population-wide data for information on patients diagnosed and treated with chronic obstructive pulmonary disease (COPD) in primary care could help inform future healthcare and spending practices. Theresa Lee at the University of Toronto, Canada, and colleagues used an algorithm to search electronic medical records and identify patients with COPD from doctors’ notes, prescriptions and symptom histories. They carefully adjusted the algorithm to improve sensitivity and predictive value by adding details such as specific medications, physician codes related to COPD, and different combinations of terminology in doctors’ notes. The team accurately identified 364 patients with COPD in a randomly-selected cohort of 5889 people. Their results suggest opportunities for broader, informative studies of COPD in wider populations.
17 citations
References
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University of Manchester1, University of Barcelona2, St George's Hospital3, University of Marburg4, University of Texas Health Science Center at San Antonio5, Imperial College London6, University of Modena and Reggio Emilia7, University of Michigan8, Hokkaido University9, University of British Columbia10
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
17,023 citations
TL;DR: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD.
Abstract: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD. The GOLD Board of Directors is grateful to the many GOLD National Leaders who participated in discussions of concepts that appear in GOLD reports.
3,165 citations
TL;DR: The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance, and there were significant benefits in all other outcomes among these patients.
Abstract: We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 μg plus fluticasone propionate at a dose of 500 μg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed. Results Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combinationtherapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P = 0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo). Conclusions The reduction in death from all causes among patients with COPD in the combinationtherapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216.)
3,037 citations
TL;DR: The St George's Respiratory Questionnaire is a standardized self-completed questionnaire for measuring impaired health and perceived well-being in airways disease and the background and rationale for its development are discussed together with an analysis of its performance.
2,621 citations
"Primary Care COPD Patients Compared..." refers methods in this paper
...We used the St Georges Respiratory Questionnaire (SGRQ) which is designed to measure health- related quality of life in patients with asthma and COPD [34]....
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TL;DR: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype, which has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity.
Abstract: BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. RESULTS: Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. CONCLUSIONS: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
2,459 citations
"Primary Care COPD Patients Compared..." refers background in this paper
...Selection for large COPD studies The proportion of patients from primary care that would be eligible to be included in the LPCS ranged from 17% (TRISTAN trial) to 42% (ECLIPSE and UPLIFT study) (Table 7)....
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...In addition to five large trials, we decided to include the ECLIPSE cohort study as well, because this is an important observational study often cited in guidelines, especially with regard to exacerbation frequency patterns....
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...Exacerbation data Individual datasets: UNLOCK studies reporting exacerbation data were compared with baseline data of the ISOLDE, TRISTAN, TORCH, UPLIFT and ECLIPSE studies (Table 3)....
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...The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT)....
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...Overall mean MRC scores were similar in the UNLOCK studies compared to ECLIPSE: 2.1 (0.8) and 2.7 (1.1), respectively....
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