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Suboptimal Medical Therapy in COPD*: Exploring the Causes and Consequences FREE TO VIEW

Scott D. Ramsey, MD, PhD
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*From the Departments of Medicine and Health Services,

Correspondence to: Scott D. Ramsey, MD, PhD, Center for Cost and Outcomes Research, University of Washington, 146 North Canal St, Suite 300, Seattle, WA 98103; e-mail: s-ramsey@u.washington.edu



Chest. 2000;117(2_suppl):33S-37S. doi:10.1378/chest.117.2_suppl.33S
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Effective outpatient management of COPD requires prescription of and adherence to appropriate therapies. Although practice guidelines for outpatient management of COPD are widely available, evidence suggests that these guidelines are not being implemented widely in clinical practice. Furthermore, several studies have shown that patient compliance with recommended therapy is poor. This paper discusses several reasons why implementation of practice guidelines and adherence with prescribed therapies may be poor. Potential clinical and economic consequences of suboptimal management are reviewed. Although the evidence suggests that improved compliance with guideline-recommended practice will improve symptoms and disease-specific quality of life, further work needs to be done to establish the cost-effectiveness of chronic therapies for COPD relative to other chronic conditions. Without such data, managed care organizations will be reluctant to allocate scarce resources toward expensive guideline implementation programs for individuals with this condition.

Figures in this Article

Effective treatment of COPD requires lifelong adherence to complicated and, for many patients, physically challenging therapies. Proper prescription and compliance with recommended therapies for COPD pose challenges to physicians and their patients. Despite the prevalence of this condition and the existence of several guidelines for managing COPD,13 appropriate use of effective interventions for COPD remains poor. Optimal management of COPD involves appropriate prescription of recommended therapies by providers and patient adherence to prescribed therapies. Although little is known about the level of physician adherence to management guidelines for COPD, it has been shown that patient compliance is particularly poor for this disease.

This article focuses on outpatient medical management—specifically, the use of inhaled bronchodilators, anti-inflammatory agents, and oxygen—discussing several factors that may explain the discrepancy between what is recommended for individuals with COPD and what actually occurs in practice. A number of physician, patient, and health system factors are identified that are likely to account for the difference between the ideal and the real. Next, the implications of suboptimal management are discussed. Here, published studies are reviewed that link specific outpatient medical interventions for COPD and clinical and economic outcomes. The article closes by suggesting several specific areas in which emphasis is warranted when implementing these complex practice guidelines, offering several observations about where future research is needed before implementation is warranted.

Stated treatment goals for outpatient management of COPD include (1) lessening airflow limitation; (2) preventing and treating secondary medical complications, such as hypoxemia and infections; and (3) decreasing respiratory symptoms and improving quality of life.1 A reasonable fourth treatment goal in a cost-conscious environment is to use health-care resources efficiently. Although published guidelines for managing COPD differ in their relative emphasis on particular therapies, they are more notable for what they have in common than for their differences. The cornerstones of management for all guidelines include smoking cessation, bronchodilator therapy, anti-inflammatory agents, oxygen, and pulmonary rehabilitation. Smoking cessation is a universal recommendation, whereas bronchodilator therapy, anti-inflammatory agents, oxygen, and pulmonary rehabilitation are based on patient-specific characteristics indicating that these treatments are warranted. A management algorithm from a representative guideline is shown in Figure 1.

Management of COPD can be suboptimal because physicians fail to prescribe appropriate therapies or because patients fail to comply with prescribed treatment regimens. Failure to prescribe appropriate therapies may be caused by underdiagnosis, lack of knowledge of the most appropriate approaches to treatment, or failure to prescribe appropriate treatments for other reasons. Although the extent to which COPD is underdiagnosed is not known, leaders in the field speculate that underdiagnosis is a significant problem.4 Very little is known about physicians’ knowledge and practice patterns for individuals with COPD. Still, there are several reasons to suspect that practitioner’s knowledge and adherence to recommended management is modest at best. The reasons are discussed in the next section.

Physician Adherence to COPD Management Guidelines

Although two consensus guidelines on management of COPD have been published in North America, the level of adherence with recommendations set forth in these guidelines is unclear.12 Data queries for this report from the 1996 National Ambulatory Medical Care Survey (a survey of patient visits to office-based physicians in the United States) suggest that individuals with COPD may not be receiving optimal therapy.5 Only 14.3% of ambulatory visits by individuals with COPD included counseling on tobacco use. Furthermore, the data suggest that both overprescription of medications with limited indications and underprescription of medications that are more universally recommended are commonplace (Table 1). For example, theophylline was prescribed at > 25% of visits, despite the fact that it is recommended as a “step 3” therapy in one leading guideline,,1 to be used only for those who fail to respond adequately to selective β2-agonists or ipratropium. Conversely, only 5% of office visits included a prescription for ipratropium, a first-line therapy.

Why would practitioners fail to comply with recommended treatment strategies for patients with COPD, particularly when guidelines derived by expert consensus panels are readily available in the literature? Those who study physician-oriented practice guidelines offer several reasons.6First, guidelines are often written as reviews of the state of knowledge (including controversies in the field) rather than blueprints for clinical practice. Busy practicing physicians often see such documents, which tend to be lengthy and not tailored to local practice situations, as user unfriendly. Second, physicians may disagree with or distrust guidelines written by expert consensus panels. Surveys suggest that most physicians tend to rely on their own experience or the recommendations of local colleagues when making treatment decisions about their patients.7 Third, physicians may ignore guidelines for other reasons, such as conflict with financial incentives or fear of malpractice litigation.

Reviews of the effect of guidelines on processes of care suggest that the most successful guidelines include elements of the following: (1) local adaptation, where practitioners are part of the adaptation process; (2) dissemination of recommendations by local opinion leaders; (3) targeting individual physicians for education using a process referred to as “academic detailing”; (4) providing feedback to physicians about how their processes of care patient outcomes compare with those of their colleagues.89 Guideline implementation efforts that include these elements appear to have a high success rate across a wide variety of diseases and treatments.8 To date, the literature does not document efforts to implement guidelines related to the care of individuals with COPD.

Although local adaptation and implementation of COPD practice guidelines is an important step toward improving the care of individuals with this disease, it is only part of the story. Successful management of COPD also involves monitoring and reinforcing effective compliance with therapy. Here, ample evidence supports the hypothesis that noncompliance is a significant barrier to improving outcomes for those with COPD.

Magnitude of Noncompliance

Several studies have found that patient compliance with COPD therapy is extremely poor. Even in the context of controlled trials, which presumably involve more intensive intervention and monitoring than standard clinical settings, compliance has been low. For example, in the Lung Health Study, patient compliance with inhaled bronchodilator therapy by self-report at follow-up year 1 was just over 60%, declining to < 50% at year 5.10Although self-report data indicate that patient compliance is wanting, studies that directly measure compliance (eg, by canister weights, nebulizer chronology, or pill counts) document an even bleaker picture of adherence to therapy. For example, the aforementioned Lung Health Study found that compliance as measured by canister weight was ≥ 10% below patient-reported compliance at all points during the period of follow-up. Furthermore, even canister weighing may overestimate compliance, because patients who are aware of this monitoring approach have been noted to “dump” their inhalers before scheduled office visits.11

Types of Noncompliance

In general, three types of noncompliance have been observed in patients with COPD on chronic therapy: undercompliance, overcompliance, and improper use. Undercompliance refers to using medications at lower than prescribed levels. Undercompliance can be sporadic (such as occasionally forgetting a dose) or systematic (such taking the medicine once a day rather than bid). Overcompliance refers to individuals ingesting their medicine at greater than prescribed schedules, either through more frequent administration, or taking higher doses at scheduled intervals, or both. Overcompliance in COPD has been observed for both inhaled medications and theophylline.1213 Improper use refers to settings in which patients use ineffective techniques to ingest their medications, regardless of whether they are maintaining dosing schedules as prescribed. Improper use can result in excess ingestion of prescribed medication, but in the case of inhaled medications such as β2-agonists, the most likely result is ingestion of suboptimal levels of medicine.15 Undercompliance is probably the most common compliance problem in COPD therapy, although improper use is also extremely common. It is important to note that more than one type of noncompliance is possible in the same individual. Thus, studies that estimate noncompliance on the basis of one type of observed behavior probably underestimate the level of the problem.

Suboptimal management of individuals with COPD may adversely affect patient outcomes and increase the cost of care for this condition. This section reviews the evidence linking the impact of specific outpatient therapies for COPD on morbidity, quality of life, and costs of care, emphasizing specific therapies where the strongest evidence exists.

Health Outcomes

With the exception of smoking cessation, there is insufficient evidence to conclude that specific outpatient therapies alter the progression of COPD. In addition, long-term oxygen therapy has been the only intervention shown to reduce mortality related to this disease. Still, studies suggest COPD-related symptoms can be reduced and quality of life can be enhanced through regular use of chronic medical therapy. Short- and long-acting bronchodilators have been shown to improve symptoms and quality of life.1618 In addition, lack of compliance with inhaled bronchodilators has been shown to adversely impact quality of life.19

Recent evidence suggests more strongly that ipratropium and chronic inhaled anti-inflammatory agents can improve outcomes for patients with COPD. In a retrospective analysis of a randomized controlled trial, Friedman and colleagues20found that adding ipratropium to salbutamol reduced exacerbations and patient days of exacerbations for those with moderate to severe COPD. Rutten-van Mölken and associates21investigated the effects of adding inhaled anti-inflammatory therapy and inhaled anticholinergics to β2-agonists in a randomized trial of 274 adult participants aged 18 to 60 years with asthma and COPD. Lung function, hyperresponsiveness, restricted activity days, and symptom-free days all improved for individuals in the inhaled corticosteroid group. An important limitation of this study was that individuals with COPD and asthma were included in the trial, and the effects of each treatment in each disease subgroup could not be established. In a multicenter, multinational, randomized, placebo-controlled trial, Paggiaro and colleagues22 found that those using inhaled fluticasone had improved spirometry values and fewer symptoms, and reduced the number of disease exacerbations compared with those who used placebo.

Good evidence exists that use of long-term inhaled oxygen in eligible subjects improves symptoms and reduces mortality related to COPD.2324 Furthermore, one study has shown that lack of compliance with long-term oxygen therapy is associated with poorer survival among patients with severe emphysema managed in the outpatient setting.25 It seems reasonable to conclude from this evidence that there is strong justification for implementing the long-term oxygen portion of COPD management guidelines, emphasizing identification and therapy (including adherence) for those who are eligible.

Economic End Points

In an era of heightened attention to the costs of medical care, it is important to establish the cost-effectiveness of interventions for chronic diseases such as COPD. Because implementation of clinical practice guidelines can be costly,26managed care organizations may be reluctant to adopt a specific guideline if it is not accompanied by evidence that doing so yields significant health gains in return for added expenditure. There is very little literature documenting the cost-effectiveness of most medical interventions for COPD.27 Because guideline implementation programs can be costly, it may be difficult for managed care organizations to justify allocating scarce resources toward aggressive implementation programs for COPD relative to other chronic diseases in which the cost-effectiveness of treatments is known.

Only two studies have evaluated the cost-effectiveness of specific medications in patients with COPD. The results are conflicting. Clinical results from the study by Rutten-van Mölken and associates21 indicated that addition of the inhaled corticosteroid to fixed-dose terbutaline led to a significant improvement in pulmonary function (FEV1 and provocative dose of substance causing 20% fall in FEV1) and symptom-free days, whereas addition of the inhaled ipratropium bromide to fixed-dose terbutaline produced no significant clinical benefits over placebo. The incremental cost-effectiveness for inhaled corticosteroid was US $201 per 10% improvement in FEV1 and $5 per symptom-free day gained. The incremental cost effectiveness of ipratropium bromide was not evaluated because of the lack of clinical benefit relative to placebo. In contrast, Freidman and colleagues,20 found that adding ipratropium to salbutamol improved pulmonary function, reduced the number of COPD exacerbations and patient-days of exacerbation, and reduced the total cost of treatment for the study period compared with salbutamol alone. Further pharmacoeconomic studies will be needed to resolve the issue of the cost-effectiveness of these and other therapies for individuals with COPD.

Outpatient medical management of individuals with COPD remains suboptimal. Although several practice guidelines are available for COPD, successful implementation of practice guidelines involves local adaptation, dissemination by opinion leaders, and academic detailing and structured physician-specific feedback of compliance in relation to peers. Currently, it does not appear that these guidelines are being widely implemented in managed care settings. This may be caused by lack of consensus among physicians regarding the value of specific therapies, or lack of evidence that specific therapies are cost-effective relative to interventions for other chronic conditions. Nevertheless, evidence exists that several therapies—including bronchodilators, anti-inflammatory agents, and long-term oxygen—improve outcomes for individuals with COPD. Perhaps the strongest economic argument in favor of adherence to clinical practice guidelines for outpatient management of COPD is that ineffective management represents a waste of resources used in the physician–patient encounter. Randomized studies evaluating the clinical efficacy and cost-effectiveness of implementing specific components of medical management of outpatient COPD would do much to convince physicians and managed care decision makers that adherence to guidelines is a worthwhile investment of time and resources.

University of Washington, Seattle, WA.

Figure Jump LinkFigure 1. Management of COPD. Reproduced with permission from Celli et al.1Grahic Jump Location
Table Graphic Jump Location
Table 1. Prescription Rate of Bronchodilators, Anti-inflammatories, or Oxygen Among Patients With COPD*
* 

Numbers represent percent of all office visits in ambulatory medical settings in 1996 in which a prescription occurred for individuals in whom COPD is a documented comorbidity (Adapted from the National Ambulatory Medical Care Survey, 19965).

 

Indicates a new prescription or refill of an existing prescription.

 

Primary, secondary, or tertiary ICD-9-CM code for asthma recorded for office visit.

Celli, BR, Snider, GL, Heffner, J, et al (1995) Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med152(suppl),S77-S120
 
Current review: guidelines for the assessment and management of chronic obstructive pulmonary disease. Can Med Assoc J 1992; 147:420–434.
 
Pearson, MG, Alderslade, R, Allen, SC, et al BTS guidelines for the management of chronic obstructive pulmonary disease: The COPD Guideline Group of the Standards of Care Committee of the BTS.Thorax1997;52(suppl 5),S1-S8
 
Snider, GL Distinguishing among asthma, chronic bronchitis, and emphysema.Chest1985;87(suppl 1),35S-39S
 
National Ambulatory Medical Care Survey. Hyattsville, MD: National Center for Health Statistics, 1996.
 
Greco, PJ, Eisenberg, JM Changing physicians’ practices.N Engl J Med1993;329,1271-1273
 
Greer, AL The state of the art versus the state of the science: the diffusion of new medical technologies into practice.Int J Technol Assess Health Care1988;4,4-26
 
Grimshaw, JM, Russell, IT Effect of clinical guidelines on medical practice: a systemic review of rigorous evaluations.Lancet1993;342,1317-1322
 
Bero, LA, Grilli, R, Grimshaw, JM, et al Closing the gap between research and practice: an overview of systemic reviews of interventions to promote the implementation of research findings: The Cochrane Effective Practice and Organization of Care Review Group.BMJ1998;317,465-468
 
Anthonisen, NR, Connett, JE, Kiley, MD, et al Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: The Lung Health Study.JAMA1994;272,1497-1505
 
Rand, CS, Wise, RA, Nides, M, et al Metered-dose inhaler adherence in a clinical trial.Am Rev Respir Dis1992;146,1559-1564
 
Chryssidis, E, Frewin, DB, Frith, PA, et al Compliance with aerosol therapy in chronic obstructive lung disease.N Z Med J1981;94,375-377
 
Dolce, JJ, Crisp, C, Manzella, B, et al Medication adherence patterns in chronic obstructive pulmonary disease.Chest1991;99,837-841
 
Goodman, DE, Israel, E, Rosenberg, M, et al The influence of age, diagnosis and gender on proper use of metered-dose inhalers.Am J Respir Crit Care Med1994;150,1256-1261
 
McFadden, ER, Jr Improper patient techniques with metered dose inhalers: clinical consequences and solutions to misuse.J Allergy Clin Immunol1995;96,278-283
 
Taylor, DR, Buick, B, Kinney, C, et al The efficacy of orally administered theophylline, inhaled salbutamol, and a combination of the two as chronic therapy in the management of chronic bronchitis with reversible air-flow obstruction.Am Rev Respir Dis1985;131,747-751
 
Guyatt, GH, Townsend, M, Pugsley, SO, et al Bronchodilators in chronic air-flow limitation: effects on airway function, exercise capacity, and quality of life.Am Rev Respir Dis1987;135,1069-1074
 
Appleton S, Smith B, Veal A, et al. Regular long-acting β-2 adrenoceptor agonists for chronic obstructive pulmonary disease. The Cochrane Library, Issue 4, 1999. Oxford: Update software. Available at: http://www.update-software.com/cochrane.htm.
 
Corden, ZM, Bosley, CM, Rees, PJ, et al Home nebulized therapy for patients with COPD: patient compliance with treatment and its relation to quality of life.Chest1997;112,1278-1282
 
Friedman, M, Serby, CW, Menjoge, SS, et al Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.Chest1999;115,635-641
 
Rutten-van Mölken, MP, van Doorslaer, EK, Jansen, MC, et al Costs and effects of inhaled corticosteroids and bronchodilators in asthma and chronic obstructive pulmonary disease.Am J Respir Crit Care Med1995;151,975-982
 
Paggiaro, PL, Dahle, R, Bakran, I, et al Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease: International COPD Study Group.Lancet1998;351,773-780
 
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of the Medical Research Council Working Party. Lancet 1981; 1:681–686.
 
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial; Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93:391–398.
 
Piccioni, P, Caria, E, Bignamini, E, et al Predictors of survival in a group of patients with chronic airflow obstruction.J Clin Epidemiol1998;51,547-555
 
Haycox, A, Bagust, A Clinical guidelines: the hidden costs.BMJ1999;318,391-393
 
Mölken, MP, van Doorslaer, EK, Rutten, FF Economic appraisal of asthma and COPD care: a literature review 1980–1991.Soc Sci Med1992;35,161-175
 

Figures

Figure Jump LinkFigure 1. Management of COPD. Reproduced with permission from Celli et al.1Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Prescription Rate of Bronchodilators, Anti-inflammatories, or Oxygen Among Patients With COPD*
* 

Numbers represent percent of all office visits in ambulatory medical settings in 1996 in which a prescription occurred for individuals in whom COPD is a documented comorbidity (Adapted from the National Ambulatory Medical Care Survey, 19965).

 

Indicates a new prescription or refill of an existing prescription.

 

Primary, secondary, or tertiary ICD-9-CM code for asthma recorded for office visit.

References

Celli, BR, Snider, GL, Heffner, J, et al (1995) Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med152(suppl),S77-S120
 
Current review: guidelines for the assessment and management of chronic obstructive pulmonary disease. Can Med Assoc J 1992; 147:420–434.
 
Pearson, MG, Alderslade, R, Allen, SC, et al BTS guidelines for the management of chronic obstructive pulmonary disease: The COPD Guideline Group of the Standards of Care Committee of the BTS.Thorax1997;52(suppl 5),S1-S8
 
Snider, GL Distinguishing among asthma, chronic bronchitis, and emphysema.Chest1985;87(suppl 1),35S-39S
 
National Ambulatory Medical Care Survey. Hyattsville, MD: National Center for Health Statistics, 1996.
 
Greco, PJ, Eisenberg, JM Changing physicians’ practices.N Engl J Med1993;329,1271-1273
 
Greer, AL The state of the art versus the state of the science: the diffusion of new medical technologies into practice.Int J Technol Assess Health Care1988;4,4-26
 
Grimshaw, JM, Russell, IT Effect of clinical guidelines on medical practice: a systemic review of rigorous evaluations.Lancet1993;342,1317-1322
 
Bero, LA, Grilli, R, Grimshaw, JM, et al Closing the gap between research and practice: an overview of systemic reviews of interventions to promote the implementation of research findings: The Cochrane Effective Practice and Organization of Care Review Group.BMJ1998;317,465-468
 
Anthonisen, NR, Connett, JE, Kiley, MD, et al Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: The Lung Health Study.JAMA1994;272,1497-1505
 
Rand, CS, Wise, RA, Nides, M, et al Metered-dose inhaler adherence in a clinical trial.Am Rev Respir Dis1992;146,1559-1564
 
Chryssidis, E, Frewin, DB, Frith, PA, et al Compliance with aerosol therapy in chronic obstructive lung disease.N Z Med J1981;94,375-377
 
Dolce, JJ, Crisp, C, Manzella, B, et al Medication adherence patterns in chronic obstructive pulmonary disease.Chest1991;99,837-841
 
Goodman, DE, Israel, E, Rosenberg, M, et al The influence of age, diagnosis and gender on proper use of metered-dose inhalers.Am J Respir Crit Care Med1994;150,1256-1261
 
McFadden, ER, Jr Improper patient techniques with metered dose inhalers: clinical consequences and solutions to misuse.J Allergy Clin Immunol1995;96,278-283
 
Taylor, DR, Buick, B, Kinney, C, et al The efficacy of orally administered theophylline, inhaled salbutamol, and a combination of the two as chronic therapy in the management of chronic bronchitis with reversible air-flow obstruction.Am Rev Respir Dis1985;131,747-751
 
Guyatt, GH, Townsend, M, Pugsley, SO, et al Bronchodilators in chronic air-flow limitation: effects on airway function, exercise capacity, and quality of life.Am Rev Respir Dis1987;135,1069-1074
 
Appleton S, Smith B, Veal A, et al. Regular long-acting β-2 adrenoceptor agonists for chronic obstructive pulmonary disease. The Cochrane Library, Issue 4, 1999. Oxford: Update software. Available at: http://www.update-software.com/cochrane.htm.
 
Corden, ZM, Bosley, CM, Rees, PJ, et al Home nebulized therapy for patients with COPD: patient compliance with treatment and its relation to quality of life.Chest1997;112,1278-1282
 
Friedman, M, Serby, CW, Menjoge, SS, et al Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.Chest1999;115,635-641
 
Rutten-van Mölken, MP, van Doorslaer, EK, Jansen, MC, et al Costs and effects of inhaled corticosteroids and bronchodilators in asthma and chronic obstructive pulmonary disease.Am J Respir Crit Care Med1995;151,975-982
 
Paggiaro, PL, Dahle, R, Bakran, I, et al Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease: International COPD Study Group.Lancet1998;351,773-780
 
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of the Medical Research Council Working Party. Lancet 1981; 1:681–686.
 
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial; Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93:391–398.
 
Piccioni, P, Caria, E, Bignamini, E, et al Predictors of survival in a group of patients with chronic airflow obstruction.J Clin Epidemiol1998;51,547-555
 
Haycox, A, Bagust, A Clinical guidelines: the hidden costs.BMJ1999;318,391-393
 
Mölken, MP, van Doorslaer, EK, Rutten, FF Economic appraisal of asthma and COPD care: a literature review 1980–1991.Soc Sci Med1992;35,161-175
 
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