Related Articles

Chronic obstructive pulmonary disease (COPD) is a spectrum of chronic lung disease. The prevalence and incidence of COPD is on the increase globally with an attendant increase in morbidity and mortality. There is a lack of data on the prevalence and incidence of chronic obstructive pulmonary disease COPD in developing countries, which is what prompted this study. We reviewed mortality due to COPD in order to identify risk factors for death and possible preventive measures. Out of 161 admissions during the review period-1990 to 1999-there were 41 deaths, accounting for a mortality rate of 25.46%. The highest mortality occurred in the sixth and seventh decades of life with a male to female ratio of 3:1. Chest infections, cor pulmonale, and respiratory failure were the most common complications. Extremes of age, lower socio-economic group, smoking (>10 packs per year), and respiratory tract infection were the most commonly identified risk factors for death. Attention should be paid to preventive measures to halt the development and progression of the disease. This offers the best hope of minimizing mortality.

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Its possible association with obstructive sleep apnea is a major cause of concern for clinicians. As the prevalence of both COPD and sleep apnea continues to rise, further investigation of this interaction is needed. In addition, COPD patients are at risk for hypoventilation during sleep due to the underlying respiratory dysfunction. In this study, 13 COPD subjects and 13 non-COPD control subjects were compared for the presence and severity of obstructive sleep apnea and nocturnal hypoventilation. All 26 subjects had presented to a sleep clinic and showed no signs of daytime hypoxemia. After matching for BMI and age, COPD subjects had a similar prevalence of sleep apnea with a lower degree of severity compared to the control subjects. However, less severe events, such as RERA, occurred at similar rates between the two groups. There was no significant difference between groups in the magnitude of oxyhemoglobin desaturation during sleep. Interestingly, severity and presence of nocturnal hypoxemia correlated with that of sleep apnea in the control group, but not in the COPD subjects. In conclusion, COPD without daytime hypoxemia was not a risk factor for sleep apnea or nocturnal hypoventilation in this study.

This review summarizes the long-term clinical outcomes associated with β-agonist and anticholinergic bronchodilator use in patients with chronic obstructive pulmonary disease (COPD). Pooled data from randomized placebo-controlled trials of at least three months duration were used to evaluate the risk for COPD hospitalizations, respiratory mortality, and total mortality. The results show that anticholinergic use is associated with a 30% reduction in COPD hospitalizations, a 70% reduction in respiratory mortality, and without a significant effect on total mortality. In contrast, β-agonist use had no effect on COPD hospitalizations and was associated with a two-fold increased risk for respiratory death compared with placebo. When the two bronchodilators were directly compared with each other, β-agonists were associated with a two-fold increased risk for COPD hospitalization and a five-fold increased risk for total mortality compared with anticholinergics. When β-agonists were added to either anticholinergic use or inhaled corticosteroid use alone, there was no significant improvement in any long-term clinical outcome. These results indicate that anticholinergics should be the bronchodilator of choice in COPD, while β-agonists may be associated with poorer disease control.

Background

A study was undertaken of deaths with an underlying or associated cause of chronic obstructive pulmonary disease (COPD), and trends in COPD mortality from 1979 to 2002 in France were analysed.

Methods

Data were obtained from the Centre of Epidemiology on the Medical Causes of Death (CépiDc) for individuals aged 45 years and over. Owing to implementation of ICD‐10 in 2000 for recording causes of death, two separate periods were analysed (1979–99 and 2000–2).

Results

In 2000–2, COPD was the underlying cause of 1.4% of deaths (deaths from COPD) and was mentioned on the death certificate in 3.0% (deaths with COPD). The other main underlying causes in these cases were cardiovascular diseases (32.0%) and cancers (24.5%). In 1979–99, age standardised rates of death with COPD remained stable in men (−0.01%/year) and increased in women (+1.7%/year). The mean annual rates of death with COPD per 100 000 were 84 for men and 19 for women in 2000–2.

Conclusion

Multiple cause analysis improved the estimate of COPD related mortality. In 1979–99, COPD related mortality rates in France were stable in men but increased in women. Implementation of ICD‐10 in 2000 introduced substantial discontinuities in mortality trends.

Background

Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death in the world, and further increases in the prevalence and mortality are predicted. Delay in diagnosing COPD appears frequently even though current consensus guidelines emphasize the importance of early detection of the disease. The aim of the present study is to evaluate the effectiveness of a screening programme in general practice.

Methods/Design

Subjects aged 65 years and older registered with a General Practitioner (GP) in the eastern Copenhagen will receive a written invitation and a simple questionnaire focusing on risk factors and symptoms of COPD. Subjects who meet the following criteria will be encouraged to undergo spirometric testing at their GP: current smokers, former smokers, and subjects with no smoking history but who have dyspnea and/or chronic cough with sputum.

Discussion

The Copenhagen COPD Screening Project evaluates the effectiveness of a two-stage screening program for COPD in general practice and provides important information on how to organize early detection of COPD in general practice in the future.

BACKGROUND:

Chronic obstructive pulmonary disease (COPD) is associated with significant mortality. It is currently the fourth leading cause of death in Canada and the world.

OBJECTIVES:

To describe the mortality of elderly patients in Ontario after hospital admission for COPD.

METHODS:

A retrospective cohort study was conducted using the Discharge Abstract Database from the Canadian Institute for Health Information. Patients aged 65 years and older who were admitted to hospital between 2001 and 2004 with primary discharge diagnoses labelled with International Classification of Diseases, Ninth Revision codes 491, 492 and 496 were included in the study.

RESULTS:

Mortality rates were 8.81, 12.10, 14.53 and 27.72 per 100 COPD hospital admissions at 30, 60, 90 and 365 days after hospital discharge, respectively. Mortality also increased with age, and men had higher rates than women. No significant differences in mortality rates were found between different socioeconomic groups (P>0.05). Patients with shared care of a family physician or general practitioner and a specialist had significantly lower mortality rates than the overall rate (P<0.05), and their rates were approximately one-half the rate of patients with only one physician.

CONCLUSIONS:

Hospitalization with COPD is associated with significant mortality. Patients who were cared for by both a family physician or general practitioner and a specialist had significantly lower mortality rates than those cared for by only one physician, suggesting that continuous and coordinated care results in better survival.

SETTING

The National Longitudinal Mortality Study (NLMS) offers the advantage of assessing mortality in a representative population of the United States.

OBJECTIVE

To evaluate health disparities associated with lung cancer and chronic obstructive pulmonary disease (COPD) mortality in the United States and whether these associations are similar between these outcomes.

DESIGN

The NLMS is a prospective study. Data are from NLMS cohort years 1985, 1992, 1993, 1995, and 1996 were included representing nearly 1.5 million person years. Lung cancer and COPD mortality relative risks from Cox regression analysis including residential characteristics, marital status, education, health insurance, and family income were evaluated.

RESULTS

By 1998, 1,273 lung cancer deaths and 772 COPD deaths occurred. Lung cancer mortality rates were approximately two times higher than COPD mortality rates among race and ethnic groups. Cox regression analysis revealed that low education (Relative Risk (RR) = 1.77, significant, p=0.01) and low family income (RR = 1.50, significant, p=0.01) are associated with lung cancer and COPD mortality controlling for age, race/ethnicity, gender and smoking status.

CONCLUSIONS

COPD and lung cancer mortality have similar associations with health disparities indicators in the NLMS data with some differences in the magnitude of the effect.

Objective

To develop a more age-appropriate spirometric definition of chronic obstructive pulmonary disease (COPD) among older persons.

Methods

Using data from the Third National Health and Nutrition Examination Survey (NHANES III), we developed a two-part spirometric definition of COPD in older persons, aged 65–80 years, that 1) determines a cut-point for the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) based on mortality risk; and 2) among persons below this critical FEV1/FVC threshold, determines cut-points for the FEV1, expressed as a standardized residual percentile (SR-tile) and based on the prevalence of respiratory symptoms and mortality risk. Measurements included spirometry, health questionnaires, and mortality (National Death Index).

Results

There were 2,480 older participants with a mean age of 71.7 years; 1,372 (55.4%) had a smoking history, 1,097 (44.2%) had respiratory symptoms and, over the course of 12-years, 868 (35.0%) had died. Among participants with an FEV1/FVC < .70 and FEV1 < 5th SR-tile, representing 7.7% of the cohort, the risk of death was doubled (adjusted hazard ratio, 2.01; 95% confidence interval [CI], 1.60–2.54). Among participants with an FEV1/FVC < .70 and FEV1 < 10th SR-tile, representing 13.4% of the cohort, the prevalence of respiratory symptoms was elevated (adjusted odds ratio, 2.44; CI, 1.79–3.33).

Conclusion

In a large, nationally representative sample of community-living older persons, defining COPD based on an FEV1/FVC < .70, with FEV1 cut-points at the 10th and 5th SR-tile, identifies individuals with an increased prevalence of respiratory symptoms and an increased risk of death, respectively.

SUMMARY

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is underdiagnosed. One barrier to diagnosis is the limited availability of spirometry testing, but in adults at risk for COPD, a normal pre-bronchodilator (pre-BD) peak expiratory flow (PEF) may rule out clinically significant COPD.

OBJECTIVE

To identify post-BD airway obstruction using data from 13 708 individuals aged ≥40 years from the PLATINO and BOLD studies.

METHODS

We evaluated different cut-off points of pre-BD. The PEF was obtained from a diagnostic-quality spirometer (not a mechanical PEF meter). At least one of the following COPD risk factors was present in 77% of the subjects: chronic respiratory symptoms; exposure to tobacco smoke, biomass smoke or dust in the workplace; or a previous diagnosis of asthma, COPD, emphysema or chronic bronchitis.

RESULTS

Although the positive predictive value was low as expected, a pre-BD PEF of ≥70% predicted effectively ruled out Stages III and IV COPD of the Global Initiative for Chronic Obstructive Lung Disease. Among those with at least one risk factor, only 12% would require confirmatory spirometry using this criterion.

CONCLUSIONS

Adding PEF measurement to a screening questionnaire may rule out severe to very severe COPD without the need for pre- and post-BD spirometry testing. Confirmation is needed from a study using inexpensive PEF meters or pocket spirometers with a staged screening protocol.

BACKGROUND—Ipratropium is commonly used for the management of elderly patients with obstructive airway disease. However, a recent report suggested that its use might be associated with a significant increase in mortality. A study was therefore conducted to compare all-cause mortality rates between users and non-users of ipratropium in elderly patients with either asthma or chronic obstructive pulmonary disease (COPD).
METHODS—A retrospective cohort study was performed using linked data from the Canadian Institute for Health Information, the Ontario Drug Benefit Program, the Ontario Health Insurance Plan, and the Ontario Registered Persons database. A total of 32 393 patients were identified who were aged 65 years or older and who had been discharged from hospital with asthma or COPD between 1 April 1992and 31 March 1997. All-cause mortality rates were compared between those treated and those not treated with ipratropium following discharge from hospital.
RESULTS—In total, 49% of patients received ipratropium within 90 days of discharge. After adjusting for age, sex, comorbidity, use of health services, and other airway medications there was no significant association in patients with COPD between the use of ipratropium and mortality (relative risk (RR) 1.03; 95% confidence interval (CI) 0.98 to 1.08). In patients with asthma, however, there was a slight increase in the relative risk of mortality associated with the use of ipratropium (RR 1.24; 95% CI 1.11 to 1.39). A dose-response increase in the mortality rate was not observed with increasing use of ipratropium in either COPD or asthma.
CONCLUSIONS—The use of ipratropium in patients with COPD was not associated with an increase in mortality. However, in asthma there was a small increase in the mortality rate. Since asthmatic patients who received ipratropium had greater use of other airway medications and health services, the difference in mortality rate between users and non-users may be a reflection of unmeasured differences in asthma severity.



Background and aim

Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD). Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.

Methods

A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000–2001. Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained. Information on long-term mortality was obtained from national registries in each of the Nordic countries.

Results

In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive. Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5). Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02). Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality. An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.

Conclusion

Almost four out of five patients died within 9 years following an admission for COPD exacerbation. Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) is a costly and deadly disease afflicting an estimated 210 million people and accounting for 5% of all global deaths. Exposure to cigarette smoke is the greatest risk factor for COPD in the developed world. Smoking cessation improves respiratory symptoms and lung function and reduces mortality among patients with COPD. Cigarette smokers with COPD and other co-morbid conditions such as cardiovascular disease and psychiatric illnesses should receive comprehensive tobacco treatment interventions incorporating efficacious pharmacotherapies. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, is the newest and most effective drug currently available to promote smoking cessation. In conjunction with behavioral interventions and clinical monitoring for potential side effects, varenicline offers great hope for reducing smoking-attributable death and disability.

Executive Summary

In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.

After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.

The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.

Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework

Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model

Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature

For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.

For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.

The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.

Objective

The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of multidisciplinary care (MDC) compared with usual care (UC, single health care provider) for the treatment of stable chronic obstructive pulmonary disease (COPD).

Clinical Need: Condition and Target Population

Chronic obstructive pulmonary disease is a progressive disorder with episodes of acute exacerbations associated with significant morbidity and mortality. Cigarette smoking is linked causally to COPD in more than 80% of cases. Chronic obstructive pulmonary disease is among the most common chronic diseases worldwide and has an enormous impact on individuals, families, and societies through reduced quality of life and increased health resource utilization and mortality.

The estimated prevalence of COPD in Ontario in 2007 was 708,743 persons.

Technology

Multidisciplinary care involves professionals from a range of disciplines, working together to deliver comprehensive care that addresses as many of the patient’s health care and psychosocial needs as possible.

Two variables are inherent in the concept of a multidisciplinary team: i) the multidisciplinary components such as an enriched knowledge base and a range of clinical skills and experiences, and ii) the team components, which include but are not limited to, communication and support measures. However, the most effective number of team members and which disciplines should comprise the team for optimal effect is not yet known.

Research Question

What is the effectiveness and cost-effectiveness of MDC compared with UC (single health care provider) for the treatment of stable COPD?

Research Methods

Literature Search

Search Strategy

A literature search was performed on July 19, 2010 using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 1995 until July 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.

Inclusion Criteria

health technology assessments, systematic reviews, or randomized controlled trials

studies published between January 1995 and July 2010;

COPD study population

studies comparing MDC (2 or more health care disciplines participating in care) compared with UC (single health care provider)

Exclusion Criteria

grey literature

duplicate publications

non-English language publications

study population less than 18 years of age

Outcomes of Interest

hospital admissions

emergency department (ED) visits

mortality

health-related quality of life

lung function

Quality of Evidence

The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.

The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:

Summary of Findings

Six randomized controlled trials were obtained from the literature search. Four of the 6 studies were completed in the United States. The sample size of the 6 studies ranged from 40 to 743 participants, with a mean study sample between 66 and 71 years of age. Only 2 studies characterized the study sample in terms of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria, and in general the description of the study population in the other 4 studies was limited. The mean percent predicted forced expiratory volume in 1 second (% predicted FEV1) among study populations was between 32% and 59%. Using this criterion, 3 studies included persons with severe COPD and 2 with moderate COPD. Information was not available to classify the population in the sixth study.

Four studies had MDC treatment groups which included a physician. All studies except 1 reported a respiratory specialist (i.e., respiratory therapist, specialist nurse, or physician) as part of the multidisciplinary team. The UC group was comprised of a single health care practitioner who may or may not have been a respiratory specialist.

A meta-analysis was completed for 5 of the 7 outcome measures of interest including:

health-related quality of life,

lung function,

all-cause hospitalization,

COPD-specific hospitalization, and

mortality.

There was only 1 study contributing to the outcome of all-cause and COPD-specific ED visits which precluded pooling data for these outcomes. Subgroup analyses were not completed either because heterogeneity was not significant or there were a small number of studies that were meta-analysed for the outcome.

Quality of Life

Three studies reported results of quality of life assessment based on the St. George’s Respiratory Questionnaire (SGRQ). A mean decrease in the SGRQ indicates an improvement in quality of life while a mean increase indicates deterioration in quality of life. In all studies the mean change score from baseline to the end time point in the MDC treatment group showed either an improvement compared with the control group or less deterioration compared with the control group. The mean difference in change scores between MDC and UC groups was statistically significant in all 3 studies. The pooled weighted mean difference in total SGRQ score was −4.05 (95% confidence interval [CI], −6.47 to 1.63; P = 0.001). The GRADE quality of evidence was assessed as low for this outcome.

Lung Function

Two studies reported results of the FEV1 % predicted as a measure of lung function. A negative change from baseline infers deterioration in lung function and a positive change from baseline infers an improvement in lung function. The MDC group showed a statistically significant improvement in lung function up to 12 months compared with the UC group (P = 0.01). However this effect is not maintained at 2-year follow-up (P = 0.24). The pooled weighted mean difference in FEV1 percent predicted was 2.78 (95% CI, −1.82 to −7.37). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.

Hospital Admissions

All-Cause

Four studies reported results of all-cause hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 4 studies were pooled to determine a summary estimate. There is a statistically significant 25% relative risk (RR) reduction in all-cause hospitalizations in the MDC group compared with the UC group (P < 0.001). The index of heterogeneity (I2) value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.

COPD-Specific Hospitalization

Three studies reported results of COPD-specific hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically significant 33% RR reduction in all-cause hospitalizations in the MDC group compared with the UC group (P = 0.002). The I2 value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.

Emergency Department Visits

All-Cause

Two studies reported results of all-cause ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically nonsignificant reduction in all-cause ED visits when data from these 2 studies are pooled (RR, 0.64; 95% CI, 0.31 to −1.33; P = 0.24). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.

COPD-Specific

One study reported results of COPD-specific ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically significant 41% reduction in COPD-specific ED visits when the data from these 2 studies are pooled (RR, 0.59; 95% CI, 0.43−0.81; P < 0.001). The GRADE quality of evidence was assessed as moderate for this outcome.

Mortality

Three studies reported the mortality during the study follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically nonsignificant reduction in mortality between treatment groups (RR, 0.81; 95% CI, 0.52−1.27; P = 0.36). The I2 value is 19%, indicating low statistical heterogeneity between studies. All studies had a 12-month follow-up period. The GRADE quality of evidence was assessed as low for this outcome.

Conclusions

Significant effect estimates with moderate quality of evidence were found for all-cause hospitalization, COPD-specific hospitalization, and COPD-specific ED visits (Table ES1). A significant estimate with low quality evidence was found for the outcome of quality of life (Table ES2). All other outcome measures were nonsignificant and supported by low or very low quality of evidence.

Summary of Dichotomous Data

Abbreviations: CI, confidence intervals; COPD, chronic obstructive pulmonary disease; n, number.

Summary of Continuous Data

Abbreviations: CI, confidence intervals; FEV1, forced expiratory volume in 1 second; n, number; SGRQ, St. George’s Respiratory Questionnaire.

Executive Summary

In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.

After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.

The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.

Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework

Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Home Telehealth for Patients with Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model

Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature

For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.

For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.

The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.

Objective

The objective of this analysis was to compare hospital-at-home care with inpatient hospital care for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) who present to the emergency department (ED).

Clinical Need: Condition and Target Population

Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease is a disease state characterized by airflow limitation that is not fully reversible. This airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The natural history of COPD involves periods of acute-onset worsening of symptoms, particularly increased breathlessness, cough, and/or sputum, that go beyond normal day-to-day variations; these are known as acute exacerbations.

Two-thirds of COPD exacerbations are caused by an infection of the tracheobronchial tree or by air pollution; the cause in the remaining cases is unknown. On average, patients with moderate to severe COPD experience 2 or 3 exacerbations each year.

Exacerbations have an important impact on patients and on the health care system. For the patient, exacerbations result in decreased quality of life, potentially permanent losses of lung function, and an increased risk of mortality. For the health care system, exacerbations of COPD are a leading cause of ED visits and hospitalizations, particularly in winter.

Technology

Hospital-at-home programs offer an alternative for patients who present to the ED with an exacerbation of COPD and require hospital admission for their treatment. Hospital-at-home programs provide patients with visits in their home by medical professionals (typically specialist nurses) who monitor the patients, alter patients’ treatment plans if needed, and in some programs, provide additional care such as pulmonary rehabilitation, patient and caregiver education, and smoking cessation counselling.

There are 2 types of hospital-at-home programs: admission avoidance and early discharge hospital-at-home. In the former, admission avoidance hospital-at-home, after patients are assessed in the ED, they are prescribed the necessary medications and additional care needed (e.g., oxygen therapy) and then sent home where they receive regular visits from a medical professional. In early discharge hospital-at-home, after being assessed in the ED, patients are admitted to the hospital where they receive the initial phase of their treatment. These patients are discharged into a hospital-at-home program before the exacerbation has resolved. In both cases, once the exacerbation has resolved, the patient is discharged from the hospital-at-home program and no longer receives visits in his/her home.

In the models that exist to date, hospital-at-home programs differ from other home care programs because they deal with higher acuity patients who require higher acuity care, and because hospitals retain the medical and legal responsibility for patients. Furthermore, patients requiring home care services may require such services for long periods of time or indefinitely, whereas patients in hospital-at-home programs require and receive the services for a short period of time only.

Hospital-at-home care is not appropriate for all patients with acute exacerbations of COPD. Ineligible patients include: those with mild exacerbations that can be managed without admission to hospital; those who require admission to hospital; and those who cannot be safely treated in a hospital-at-home program either for medical reasons and/or because of a lack of, or poor, social support at home.

The proposed possible benefits of hospital-at-home for treatment of exacerbations of COPD include: decreased utilization of health care resources by avoiding hospital admission and/or reducing length of stay in hospital; decreased costs; increased health-related quality of life for patients and caregivers when treated at home; and reduced risk of hospital-acquired infections in this susceptible patient population.

Ontario Context

No hospital-at-home programs for the treatment of acute exacerbations of COPD were identified in Ontario. Patients requiring acute care for their exacerbations are treated in hospitals.

Research Question

What is the effectiveness, cost-effectiveness, and safety of hospital-at-home care compared with inpatient hospital care of acute exacerbations of COPD?

Research Methods

Literature Search

Search Strategy

A literature search was performed on August 5, 2010, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published from January 1, 1990, to August 5, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists and health technology assessment websites were also examined for any additional relevant studies not identified through the systematic search.

Inclusion Criteria

English language full-text reports;

health technology assessments, systematic reviews, meta-analyses, and randomized controlled trials (RCTs);

studies performed exclusively in patients with a diagnosis of COPD or studies including patients with COPD as well as patients with other conditions, if results are reported for COPD patients separately;

studies performed in patients with acute exacerbations of COPD who present to the ED;

studies published between January 1, 1990, and August 5, 2010;

studies comparing hospital-at-home and inpatient hospital care for patients with acute exacerbations of COPD;

studies that include at least 1 of the outcomes of interest (listed below).

Cochrane Collaboration reviews have defined hospital-at-home programs as those that provide patients with active treatment for their acute exacerbation in their home by medical professionals for a limited period of time (in this case, until the resolution of the exacerbation). If a hospital-at-home program had not been available, these patients would have been admitted to hospital for their treatment.

Exclusion Criteria

< 18 years of age

animal studies

duplicate publications

grey literature

Outcomes of Interest

Patient/clinical outcomes

mortality

lung function (forced expiratory volume in 1 second)

health-related quality of life

patient or caregiver preference

patient or caregiver satisfaction with care

complications

Health system outcomes

hospital readmissions

length of stay in hospital and hospital-at-home

ED visits

transfer to long-term care

days to readmission

eligibility for hospital-at-home

Statistical Methods

When possible, results were pooled using Review Manager 5 Version 5.1; otherwise, results were summarized descriptively. Data from RCTs were analyzed using intention-to-treat protocols. In addition, a sensitivity analysis was done assigning all missing data/withdrawals to the event. P values less than 0.05 were considered significant. A priori subgroup analyses were planned for the acuity of hospital-at-home program, type of hospital-at-home program (early discharge or admission avoidance), and severity of the patients’ COPD. Additional subgroup analyses were conducted as needed based on the identified literature. Post hoc sample size calculations were performed using STATA 10.1.

Quality of Evidence

The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.

The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:

Summary of Findings

Fourteen studies met the inclusion criteria and were included in this review: 1 health technology assessment, 5 systematic reviews, and 7 RCTs.

The following conclusions are based on low to very low quality of evidence. The reviewed evidence was based on RCTs that were inadequately powered to observe differences between hospital-at-home and inpatient hospital care for most outcomes, so there is a strong possibility of type II error. Given the low to very low quality of evidence, these conclusions must be considered with caution.

Approximately 21% to 37% of patients with acute exacerbations of COPD who present to the ED may be eligible for hospital-at-home care.

Of the patients who are eligible for care, some may refuse to participate in hospital-at-home care.

Eligibility for hospital-at-home care may be increased depending on the design of the hospital-at-home program, such as the size of the geographical service area for hospital-at-home and the hours of operation for patient assessment and entry into hospital-at-home.

Hospital-at-home care for acute exacerbations of COPD was associated with a nonsignificant reduction in the risk of mortality and hospital readmissions compared with inpatient hospital care during 2- to 6-month follow-up.

Limited, very low quality evidence suggests that hospital readmissions are delayed in patients who received hospital-at-home care compared with those who received inpatient hospital care (mean additional days before readmission comparing hospital-at-home to inpatient hospital care ranged from 4 to 38 days).

There is insufficient evidence to determine whether hospital-at-home care, compared with inpatient hospital care, is associated with improved lung function.

The majority of studies did not find significant differences between hospital-at-home and inpatient hospital care for a variety of health-related quality of life measures at follow-up. However, follow-up may have been too late to observe an impact of hospital-at-home care on quality of life.

A conclusion about the impact of hospital-at-home care on length of stay for the initial exacerbation (defined as days in hospital or days in hospital plus hospital-at-home care for inpatient hospital and hospital-at-home, respectively) could not be determined because of limited and inconsistent evidence.

Patient and caregiver satisfaction with care is high for both hospital-at-home and inpatient hospital care.

Background: A study was undertaken to define the risk of death among a national cohort of US adults both with and without lung disease.

Methods: Participants in the first National Health and Nutrition Examination Survey (NHANES I) followed for up to 22 years were studied. Subjects were classified using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD) into the following mutually exclusive categories using the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and the presence of respiratory symptoms: severe COPD, moderate COPD, mild COPD, respiratory symptoms only, restrictive lung disease, and no lung disease. Proportional hazard models were developed that controlled for age, race, sex, education, smoking status, pack years of smoking, years since quitting smoking, and body mass index.

Results: A total of 1301 deaths occurred in the 5542 adults in the cohort. In the adjusted proportional hazards model the presence of severe or moderate COPD was associated with a higher risk of death (hazard ratios (HR) 2.7 and 1.6, 95% confidence intervals (CI) 2.1 to 3.5 and 1.4 to 2.0), as was restrictive lung disease (HR 1.7, 95% CI 1.4 to 2.0).

Conclusions: The presence of both obstructive and restrictive lung disease is a significant predictor of earlier death in long term follow up.

Executive Summary

In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.

After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.

The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.

Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework

Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Hospital-at-Home Programs for Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis

Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model

Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature

For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.

For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.

The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.

Objective

The objective of this analysis was to determine the effectiveness of the influenza vaccination and the pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) in reducing the incidence of influenza-related illness or pneumococcal pneumonia.

Clinical Need: Condition and Target Population

Influenza Disease

Influenza is a global threat. It is believed that the risk of a pandemic of influenza still exists. Three pandemics occurred in the 20th century which resulted in millions of deaths worldwide. The fourth pandemic of H1N1 influenza occurred in 2009 and affected countries in all continents.

Rates of serious illness due to influenza viruses are high among older people and patients with chronic conditions such as COPD. The influenza viruses spread from person to person through sneezing and coughing. Infected persons can transfer the virus even a day before their symptoms start. The incubation period is 1 to 4 days with a mean of 2 days. Symptoms of influenza infection include fever, shivering, dry cough, headache, runny or stuffy nose, muscle ache, and sore throat. Other symptoms such as nausea, vomiting, and diarrhea can occur.

Complications of influenza infection include viral pneumonia, secondary bacterial pneumonia, and other secondary bacterial infections such as bronchitis, sinusitis, and otitis media. In viral pneumonia, patients develop acute fever and dyspnea, and may further show signs and symptoms of hypoxia. The organisms involved in bacterial pneumonia are commonly identified as Staphylococcus aureus and Hemophilus influenza. The incidence of secondary bacterial pneumonia is most common in the elderly and those with underlying conditions such as congestive heart disease and chronic bronchitis.

Healthy people usually recover within one week but in very young or very old people and those with underlying medical conditions such as COPD, heart disease, diabetes, and cancer, influenza is associated with higher risks and may lead to hospitalization and in some cases death. The cause of hospitalization or death in many cases is viral pneumonia or secondary bacterial pneumonia. Influenza infection can lead to the exacerbation of COPD or an underlying heart disease.

Streptococcal Pneumonia

Streptococcus pneumoniae, also known as pneumococcus, is an encapsulated Gram-positive bacterium that often colonizes in the nasopharynx of healthy children and adults. Pneumococcus can be transmitted from person to person during close contact. The bacteria can cause illnesses such as otitis media and sinusitis, and may become more aggressive and affect other areas of the body such as the lungs, brain, joints, and blood stream. More severe infections caused by pneumococcus are pneumonia, bacterial sepsis, meningitis, peritonitis, arthritis, osteomyelitis, and in rare cases, endocarditis and pericarditis.

People with impaired immune systems are susceptible to pneumococcal infection. Young children, elderly people, patients with underlying medical conditions including chronic lung or heart disease, human immunodeficiency virus (HIV) infection, sickle cell disease, and people who have undergone a splenectomy are at a higher risk for acquiring pneumococcal pneumonia.

Technology

Influenza and Pneumococcal Vaccines

Trivalent Influenza Vaccines in Canada

In Canada, 5 trivalent influenza vaccines are currently authorized for use by injection. Four of these are formulated for intramuscular use and the fifth product (Intanza®) is formulated for intradermal use.

The 4 vaccines for intramuscular use are:

Fluviral (GlaxoSmithKline), split virus, inactivated vaccine, for use in adults and children ≥ 6 months;

Vaxigrip (Sanofi Pasteur), split virus inactivated vaccine, for use in adults and children ≥ 6 months;

Agriflu (Novartis), surface antigen inactivated vaccine, for use in adults and children ≥ 6 months; and

Influvac (Abbott), surface antigen inactivated vaccine, for use in persons ≥ 18 years of age.

FluMist is a live attenuated virus in the form of an intranasal spray for persons aged 2 to 59 years. Immunization with current available influenza vaccines is not recommended for infants less than 6 months of age.

Pneumococcal Vaccine

Pneumococcal polysaccharide vaccines were developed more than 50 years ago and have progressed from 2-valent vaccines to the current 23-valent vaccines to prevent diseases caused by 23 of the most common serotypes of S pneumoniae. Canada-wide estimates suggest that approximately 90% of cases of pneumococcal bacteremia and meningitis are caused by these 23 serotypes. Health Canada has issued licenses for 2 types of 23-valent vaccines to be injected intramuscularly or subcutaneously:

Pneumovax 23® (Merck & Co Inc. Whitehouse Station, NJ, USA), and

Pneumo 23® (Sanofi Pasteur SA, Lion, France) for persons 2 years of age and older.

Other types of pneumococcal vaccines licensed in Canada are for pediatric use. Pneumococcal polysaccharide vaccine is injected only once. A second dose is applied only in some conditions.

Research Questions

What is the effectiveness of the influenza vaccination and the pneumococcal vaccination compared with no vaccination in COPD patients?

What is the safety of these 2 vaccines in COPD patients?

What is the budget impact and cost-effectiveness of these 2 vaccines in COPD patients?

Research Methods

Literature search

Search Strategy

A literature search was performed on July 5, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 to July 5, 2010. The search was updated monthly through the AutoAlert function of the search up to January 31, 2011. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. Data extraction was carried out by the author.

Inclusion Criteria

studies comparing clinical efficacy of the influenza vaccine or the pneumococcal vaccine with no vaccine or placebo;

randomized controlled trials published between January 1, 2000 and January 31, 2011;

studies including patients with COPD only;

studies investigating the efficacy of types of vaccines approved by Health Canada;

English language studies.

Exclusion Criteria

non-randomized controlled trials;

studies investigating vaccines for other diseases;

studies comparing different variations of vaccines;

studies in which patients received 2 or more types of vaccines;

studies comparing different routes of administering vaccines;

studies not reporting clinical efficacy of the vaccine or reporting immune response only;

studies investigating the efficacy of vaccines not approved by Health Canada.

Outcomes of Interest

Primary Outcomes

Influenza vaccination: Episodes of acute respiratory illness due to the influenza virus.

Pneumococcal vaccination: Time to the first episode of community-acquired pneumonia either due to pneumococcus or of unknown etiology.

Secondary Outcomes

rate of hospitalization and mechanical ventilation

mortality rate

adverse events

Quality of Evidence

The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses. The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:

Summary of Efficacy of the Influenza Vaccination in Immunocompetent Patients With COPD

Clinical Effectiveness

The influenza vaccination was associated with significantly fewer episodes of influenza-related acute respiratory illness (ARI). The incidence density of influenza-related ARI was:

All patients: vaccine group: (total of 4 cases) = 6.8 episodes per 100 person-years; placebo group: (total of 17 cases) = 28.1 episodes per 100 person-years, (relative risk [RR], 0.2; 95% confidence interval [CI], 0.06−0.70; P = 0.005).

Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] < 50% predicted): vaccine group: (total of 1 case) = 4.6 episodes per 100 person-years; placebo group: (total of 7 cases) = 31.2 episodes per 100 person-years, (RR, 0.1; 95% CI, 0.003−1.1; P = 0.04).

Patients with moderate airflow obstruction (FEV1 50%−69% predicted): vaccine group: (total of 2 cases) = 13.2 episodes per 100 person-years; placebo group: (total of 4 cases) = 23.8 episodes per 100 person-years, (RR, 0.5; 95% CI, 0.05−3.8; P = 0.5).

Patients with mild airflow obstruction (FEV1 ≥ 70% predicted): vaccine group: (total of 1 case) = 4.5 episodes per 100 person-years; placebo group: (total of 6 cases) = 28.2 episodes per 100 person-years, (RR, 0.2; 95% CI, 0.003−1.3; P = 0.06).

The Kaplan-Meier survival analysis showed a significant difference between the vaccinated group and the placebo group regarding the probability of not acquiring influenza-related ARI (log-rank test P value = 0.003). Overall, the vaccine effectiveness was 76%. For categories of mild, moderate, or severe COPD the vaccine effectiveness was 84%, 45%, and 85% respectively.

With respect to hospitalization, fewer patients in the vaccine group compared with the placebo group were hospitalized due to influenza-related ARIs, although these differences were not statistically significant. The incidence density of influenza-related ARIs that required hospitalization was 3.4 episodes per 100 person-years in the vaccine group and 8.3 episodes per 100 person-years in the placebo group (RR, 0.4; 95% CI, 0.04−2.5; P = 0.3; log-rank test P value = 0.2). Also, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD.

Fewer patients in the vaccine group compared with the placebo group required mechanical ventilation due to influenza-related ARIs. However, these differences were not statistically significant. The incidence density of influenza-related ARIs that required mechanical ventilation was 0 episodes per 100 person-years in the vaccine group and 5 episodes per 100 person-years in the placebo group (RR, 0.0; 95% CI, 0−2.5; P = 0.1; log-rank test P value = 0.4). In addition, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD. The effectiveness of the influenza vaccine in preventing influenza-related ARIs and influenza-related hospitalization was not related to age, sex, severity of COPD, smoking status, or comorbid diseases.

safety

Overall, significantly more patients in the vaccine group than the placebo group experienced local adverse reactions (vaccine: 17 [27%], placebo: 4 [6%]; P = 0.002). Significantly more patients in the vaccine group than the placebo group experienced swelling (vaccine 4, placebo 0; P = 0.04) and itching (vaccine 4, placebo 0; P = 0.04). Systemic reactions included headache, myalgia, fever, and skin rash and there were no significant differences between the 2 groups for these reactions (vaccine: 47 [76%], placebo: 51 [81%], P = 0.5).

With respect to lung function, dyspneic symptoms, and exercise capacity, there were no significant differences between the 2 groups at 1 week and at 4 weeks in: FEV1, maximum inspiratory pressure at residual volume, oxygen saturation level of arterial blood, visual analogue scale for dyspneic symptoms, and the 6 Minute Walking Test for exercise capacity.

There was no significant difference between the 2 groups with regard to the probability of not acquiring total ARIs (influenza-related and/or non-influenza-related); (log-rank test P value = 0.6).

Summary of Efficacy of the Pneumococcal Vaccination in Immunocompetent Patients With COPD

Clinical Effectiveness

The Kaplan-Meier survival analysis showed no significant differences between the group receiving the penumoccocal vaccination and the control group for time to the first episode of community-acquired pneumonia due to pneumococcus or of unknown etiology (log-rank test 1.15; P = 0.28). Overall, vaccine efficacy was 24% (95% CI, −24 to 54; P = 0.33).

With respect to the incidence of pneumococcal pneumonia, the Kaplan-Meier survival analysis showed a significant difference between the 2 groups (vaccine: 0/298; control: 5/298; log-rank test 5.03; P = 0.03).

Hospital admission rates and median length of hospital stays were lower in the vaccine group, but the difference was not statistically significant. The mortality rate was not different between the 2 groups.

Subgroup Analysis

The Kaplan-Meier survival analysis showed significant differences between the vaccine and control groups for pneumonia due to pneumococcus and pneumonia of unknown etiology, and when data were analyzed according to subgroups of patients (age < 65 years, and severe airflow obstruction FEV1 < 40% predicted). The accumulated percentage of patients without pneumonia (due to pneumococcus and of unknown etiology) across time was significantly lower in the vaccine group than in the control group in patients younger than 65 years of age (log-rank test 6.68; P = 0.0097) and patients with a FEV1 less than 40% predicted (log-rank test 3.85; P = 0.0498).

Vaccine effectiveness was 76% (95% CI, 20−93; P = 0.01) for patients who were less than 65 years of age and −14% (95% CI, −107 to 38; P = 0.8) for those who were 65 years of age or older. Vaccine effectiveness for patients with a FEV1 less than 40% predicted and FEV1 greater than or equal to 40% predicted was 48% (95% CI, −7 to 80; P = 0.08) and −11% (95% CI, −132 to 47; P = 0.95), respectively. For patients who were less than 65 years of age (FEV1 < 40% predicted), vaccine effectiveness was 91% (95% CI, 35−99; P = 0.002).

Cox modelling showed that the effectiveness of the vaccine was dependent on the age of the patient. The vaccine was not effective in patients 65 years of age or older (hazard ratio, 1.53; 95% CI, 0.61−a2.17; P = 0.66) but it reduced the risk of acquiring pneumonia by 80% in patients less than 65 years of age (hazard ratio, 0.19; 95% CI, 0.06−0.66; P = 0.01).

safety

No patients reported any local or systemic adverse reactions to the vaccine.

Background

Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide. Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD. The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied.

Objectives

We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden.

Methods

Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study. The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage. The cost and quality adjusted life years (QALYs) associated with each intervention were estimated.

Results

The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach $3.61B ($7.33B undiscounted) per year in 2035. Over the next 25 years, COPD will be responsible for approximately $101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted). Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations. Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada.

Conclusion

Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates.

Objective

Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD.

Design, Setting, and Participants

This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database.

Main Outcome Measures

Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment.

Results

The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768–2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD.

Conclusions

Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients.

Objective. The primary objective of the study was to estimate the rates of polypharmacy among individuals with multimorbidity defined as chronic condition clusters and examine their associations with polypharmacy. Methods. Cross-sectional analysis of 10,528 individuals of age above 21, with at least one physical condition in cardiometabolic (diabetes or heart disease or hypertension), musculoskeletal (arthritis or osteoporosis), and respiratory (chronic obstructive pulmonary disease (COPD) or asthma) clusters from the 2009 Medical Expenditure Panel Survey. Chi-square tests and logistic regressions were performed to analyze the association between polypharmacy and multimorbidity. Results. Polypharmacy rates varied from a low of 7.2% among those with respiratory cluster to a high of 64.1% among those with all three disease clusters. Among those with two or more disease clusters, the rates varied from 28.3% for musculoskeletal and respiratory clusters to 41.8% for those with cardiometabolic and respiratory clusters. Individual with cardiometabolic conditions alone or in combination with other disease clusters were more likely to have polypharmacy. Compared to those with musculoskeletal and respiratory conditions, those with cardiometabolic and respiratory conditions had 1.68 times higher likelihood of polypharmacy. Conclusions. Rates of polypharmacy differed by specific disease clusters. Individuals with cardiometabolic condition were particularly at high risk of polypharmacy, suggesting greater surveillance for adverse drug interaction in this group.

Background

The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.

Methods

The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990–2005, using the healthcare databases from the province of Quebec, Canada. Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified. The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.

Results

The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively. The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th. The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first. Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.

Conclusions

The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation. Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

Objective

To determine the burden of chronic obstructive pulmonary disease (COPD) on all-cause mortality in Blacks and Whites from four U.S. communities.

Methods

We determined prospectively the risk of death through December 2004 in relation to baseline (1987–1989) COPD status in 10,333 Black and White participants of the Atherosclerosis Risk in Communities (ARIC) study.

Results

Over a mean follow-up of 15 years (maximum 18 years), 462 deaths occurred in Blacks and 1221 deaths occurred in Whites. Hazard ratios for all-cause mortality among Blacks and Whites were similar (hazard ratio [HR]=1.74 in Blacks and HR=1.59 in Whites), indicating a 59–74% greater risk of mortality for those with COPD. However, for both those with and without COPD, crude death rates were approximately double in Blacks compared to Whites.

Conclusions

Our findings suggest that given COPD, Blacks and Whites have the same proportionate increase in mortality and that the difference in death rates between Blacks and Whites cannot be explained by COPD status. The public health burden of COPD is enormous, and strategies to reduce COPD and smoking could have a large impact on total mortality rates of both Blacks and Whites.

Background:

Several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.

Methods:

We used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV1); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.

Results:

COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043–6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014–29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07–0.27; P < 0.0001).

Conclusion:

COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Although the main risk factor is smoking, 15–19% of COPD even in smokers has been attributed to occupational exposures. The aim of this study was to investigate the association between occupational exposure and risk of COPD.

Methods: Participants were part of a cross sectional study of risk factors for COPD. A total of 1232 completed a detailed respiratory questionnaire, spirometric testsing and measurement of gas transfer. Job histories were coded according to the International Standard Classification of Occupations. These codes were then used to establish occupational exposures using the ALOHA job exposure matrix.

Results: The prevalence of emphysema was 2.4%, chronic obstructive bronchitis 1.8%, and COPD 3.4%. Subjects ever exposed to biological dusts had an increased risk of chronic obstructive bronchitis (OR 3.19; 95% CI 1.27 to 7.97), emphysema (OR 3.18; 95% CI 1.41 to 7.13), and COPD (OR 2.70, 95% CI 1.39 to 5.23). These risks were higher in women than in men. For biological dust, the risk of emphysema and COPD was also significantly increased in both the duration of exposure categories, again in women but not in men. No significant increased risks for COPD were found for mineral dust (OR 1.13; 95% CI 0.57 to 2.27) or gases/fumes (OR 1.63; 95% CI 0.83 to 3.22).

Conclusion: In this general population sample of adults, occupational exposures to biological dusts were associated with an increased risk of COPD which was higher in women. Preventive strategies should be aimed at reducing exposure to these agents in the workplace.

BACKGROUND: Studies of mortality from asthma and chronic obstructive pulmonary disease (COPD) have relied on death certification or registration for case finding. The aim of this study was to determine the accuracy of death certification and registration in asthma and COPD. METHODS: All death certificates in Northern Ireland for 1987 where asthma or COPD (defined as International Classification of Diseases 9th Revision (ICD9) 490, 491, 492, 496) were listed in part I or part II were identified. The following certificates were then selected for further investigation: those mentioning asthma for all ages, those mentioning COPD for ages less than 56 years, and a 50% sample of those mentioning COPD aged 56-75 years. For these selected deaths the general practitioners' case notes, hospital records, and necropsy findings were reviewed. Questionnaires detailing the clinical history and circumstances of death were completed by the general practitioner by post and by a close relative or associate of the deceased (doctor administered) if, after initial investigation, the death was likely to be due to COPD or asthma. A panel of two respiratory physicians reviewed each death and, using clinical diagnostic criteria, assessed the accuracy of the registered cause of death. RESULTS: Of 50 registered asthma deaths 43 were confirmed as being due to asthma. In nine registered deaths from COPD in cases aged less than 56 years one was confirmed as COPD, two as asthma, and six as other respiratory conditions. Of 105 registered deaths from COPD in cases aged 56-75, 42 were confirmed as COPD, 27 as asthma, eight as other respiratory conditions, and 28 as other causes. Although few errors in registration were found, 21% of certificates mentioning asthma and 38% of certificates mentioning COPD but not asthma in part I were subject to variable application of the classification rules by the registering officers. For all deaths under 75 years of age in Northern Ireland in 1987 where either asthma or COPD was mentioned anywhere on the death certificate, the estimated sensitivity and specificity of the registered cause of death in predicting the "true" cause of death were 29% and 98.6% for asthma and 69% and 70% for COPD. CONCLUSIONS: In a population of subjects where asthma or COPD was mentioned anywhere on the death certificate, the registered cause of death is a relatively poor indicator of the "true" cause of death for both asthma and COPD. Variation occurred in the application of death classification rules by registration officers. Many deaths certified and registered as COPD could have been called asthma using current standards of clinical diagnosis. In studies investigating risk factors for deaths from asthma, case finding should consider deaths registered as COPD.

Despite recommendations for annual vaccination against influenza, more than half of patients with chronic obstructive pulmonary disease (COPD) in developed countries do not receive this vaccine. Influenza is characterized by its potentially of causing epidemics and by excess morbidity and mortality in patients with COPD and other chronic medical conditions. Good evidence of the efficacy, effectiveness, and cost-effectiveness of influenza vaccination underlines the recommendation of use in patients with COPD. Influenza vaccination could reduce influenza-related complications and exacerbations in patients with COPD, therefore reducing hospitalizations and deaths. Each year, all persons with COPD should be vaccinated with the inactivated trivalent influenza vaccine containing the most frequent two influenza A viral strains and one influenza B viral strain detected in the influenza season of the previous year. To achieve a 100% vaccination rate in patients with COPD, all patients with COPD registered in health insurance companies and attended in health centers and specialized clinics should be vaccinated during the immunization period (October–December). Antiviral therapies could be used as an adjunct to vaccination and to reduce influenza transmission in outbreaks. Antiviral therapies could reduce the duration and complications of influenza when administered within two days of the onset of illness. Research is necessary for new antiviral therapies that could prevent influenza with cost-effectiveness similar to the influenza vaccine.