REVIEW URRENT C OPINION

Nonadherence in chronic obstructive pulmonary disease patients: what do we know and what should we do next? Bruce G. Bender

Purpose of review Although nonadherence research in patients with chronic obstructive pulmonary disease (COPD) lags well behind other diseases, new evidence helps inform understanding about the degree and underlying causes of patient nonadherence, interventions that can improve adherence, and areas of research needed to further progress in improving this problem in patients with COPD. Recent findings Fewer than half of treatments for COPD, including oxygen supplementation, physical rehabilitation, and medication, are taken as prescribed. Most patients abandon their treatment after an initial start. Nonadherence in turn contributes to rising rates of hospitalization, death, and healthcare costs. The reasons why patients choose not to use their COPD treatments are not fully understood, although depression is clearly a contributing factor. Although a substantial number of studies have tested adherence interventions, few have included COPD patients or addressed polypharmacy in patients with multiple comorbidities. Summary The paucity of research does not reflect the inadequacy of available treatments. Lessons learned from the research outside of COPD and a small number of COPD studies suggest that a collaborative care approach will likely provide the most potential for improving overall care, including management of depression and enhancement of adherence. Exploitation of mobile telephone technology to engage patients in a discussion of their self-care should not be ignored as a potential intervention for COPD patients. Video abstract http://links.lww.com/COPM/A10 Keywords adherence, COPD, interventions

INTRODUCTION Patients with chronic obstructive pulmonary disease (COPD) receive considerably fewer therapies for their disease than are available or prescribed. Two root causes are identifiable. Healthcare providers, particularly primary care providers, may not diagnose COPD or prescribe medications, supplemental oxygen, or pulmonary rehabilitation in accordance with the evidence-based guidelines [1,2 ]. Secondly, even where prescribed, patients often do not consistently follow their treatment plan; in many cases, COPD patients start but then abandon their treatment [3]. The incidence, causes, and solutions to the problem of nonadherence in COPD have received only a fraction of the attention given to this problem in other chronic conditions, but

emerging evidence is beginning to help guide healthcare providers. This article will review the current evidence about the degree and underlying causes of patient nonadherence, interventions that can improve adherence, and areas of research needed to further progress in improving this problem in patients with COPD.

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Department of Pediatrics, National Jewish Health, Denver, Colorado, USA Correspondence to Bruce G. Bender, PhD, Professor and Head, Pediatric Behavioral Health, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. Tel: +1 303 397 1697; fax: +1 303 270 2141; e-mail: [email protected] Curr Opin Pulm Med 2014, 20:132–137 DOI:10.1097/MCP.0000000000000027 Volume 20  Number 2  March 2014

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Nonadherence in chronic obstructive pulmonary disease Bender

KEY POINTS  Treatment nonadherence in COPD is documented in the uptake of all therapies, including oxygen supplementation, physical rehabilitation, and medication, and contributes to rising rates of hospitalization, death, and healthcare costs.  Factors that undermine adherence include depression and comorbidities, but the causes of nonadherence in COPD are not completely understood.  Research into interventions for COPD nonadherence lags behind other chronic diseases, but collaborative care strategies appear to improve adherence and should be tested more completely in this population.

EPIDEMIOLOGY OF UNDERTREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS Data from the U.S. Centers for Disease Control and Prevention indicate that approximately 24 million Americans have COPD [4]. Effective treatments do not reach or are not sustained for many of these patients. Despite the high prevalence of COPD, only half of the individuals with COPD have been diagnosed [5], and where COPD is identified, most primary care providers do not utilize the current evidence-based guidelines for its management [6]. A study of patients hospitalized for the first time for COPD found that 35% were previously undiagnosed and 44% were not receiving treatment for COPD [7]. Treatments for COPD may include smoking cessation intervention, supplemental oxygen, pulmonary rehabilitation, and medications. Smoking cessation and oxygen supplementation can substantially improve survival, reduce decline in lung function, and reduce exacerbations in patients with COPD, but only if prescribed by providers and used by patients [8]. Even when prescribed, fewer than half of patients use oxygen [9 ] and fewer than 30% approach full adherence [10]. Further, more than 75% of COPD patients refuse to use oxygen therapy outside of their home [11]. Pulmonary rehabilitation with life-long continued regular exercise improves patient outcomes (dyspnea, health status, and exacerbations) and yet it is infrequently prescribed, and patients do not incorporate exercise in their daily routine [12]. Recent reports from the United Kingdom indicate that only 9% of 448 hospitalization discharges for COPD included referrals for pulmonary rehabilitation [13]. Where referrals were made, 60% of patients either did not attend or began attending and then stopped [14]. Long-acting beta2 agonists (LABAs) and inhaled corticosteroids (ICS) are among the most common &

COPD medications, but the majority of prescribed medicine is never taken, and half of patients abandon inhaled treatment in the first year after it is prescribed [15,16,17 ]. In an analysis of claims data for 55 076 patients, mean 12-month adherence with inhaled COPD medications averaged 43.3, 37, 30, and 23% for once daily, twice daily, and three and four times a day prescriptions, respectively [18]. Although universally poor, adherence varies modestly between medications; ICS adherence averaged 19.8% and LABA adherence 25.6% in a Veterans’ Administration database [19 ]. Further than 12 months following initial prescription, medication use comes to a halt for most patients. Pharmacy database refill data indicated that discontinuation of refills was at 90 and 86% in year 2, falling to 94 and 92% by year 3 for patients on LABA and LABA–ICS, respectively [3]. Nonadherence is not without consequences. Decreasing medication adherence is associated with increasing COPD symptoms [20], hospitalizations [21 ], mortality [16], and cost [18,21 ]. Risk of hospitalization or death increased by 58 and 40%, respectively, in COPD patients who were nonadherent to combination inhaled steroid and LABA [22]. &&

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Assessment of recent findings Research on adherence to COPD treatments is starting to catch up research into other chronic conditions, and although the recent COPD literature represents only a fraction of the existing nonadherence literature for diabetes, hypertension, and asthma, the results are similar. Nonadherence is an enormous problem, with fewer than half of prescribed therapies being delivered to patients. As adherence declines, outcomes worsen.

CORRELATES OF NONADHERENCE The development of successful interventions to change patient behavior must follow from a clear understanding of the underlying reasons for nonadherence. Interventions based on misperceptions about the causes of nonadherence frequently fail. As one example, the presumption that patient nonadherence is because of inadequate information has sometimes led to disappointing educational interventions [23]. Recent COPD literature has documented numerous correlates of nonadherence. Decreased adherence has been associated with high cost of medication, increased age, current smoking, and irregular clinic attendance [17 ,24,25 ,26 ]. Low expectation of the medication, presence of comorbid illnesses, depressed mood, and lack of confidence in the provider emerge as the most

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consistent independent predictors of low adherence [17 ,25 ]. More than half of COPD patients suffer from anxiety or depression [27,28], almost triple the rate for an age-comparable population [29]. The association between depression and nonadherence in COPD is strong [30], although how depression undermines adherence is not fully understood and no studies have shown that treatment for depression increases adherence. &&

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Assessment of recent findings The emergence of recent reports utilizing pharmacy databases has provided new information about the factors that appear to contribute to treatment nonadherence. Although these reports often carry the implicit assertion that identifying the correlates of nonadherence provides insight into how to address this problem, this is seldom the case. Recognizing that correlation does not prove causation, the presence of a statistically significant association does not explain why nonadherence occurs. For example, the observation that patients who smoke are also less likely to take their medication does not reveal why the patient is nonadherent or how to motivate greater adherence. Still missing are reports based on direct interviews or focus groups with COPD patients, in which patients are queried about how they reach decisions to take or abandon a prescribed intervention. Such information allows for the development of adherence interventions targeting patient concerns.

INTERVENTIONS TO IMPROVE ADHERENCE Numerous adherence interventions have been tested in randomized controlled trials (RCTs), but few of these have included COPD patients. Smoking cessation programs are the sole area of behavioral research well tested with COPD patients. These RCTs are largely focused on smoking-cessation medications [31–33], but also include behavioral and educational interventions [34 ,35]. Aside from tobacco-targeted behavior change research, most adherence studies have not included COPD patients. A recent systematic review identified 62 RCTs representing 18 different interventions designed to improve adherence to medications for chronic diseases [36 ]. Reminder calls, education, behavioral support, ongoing monitoring, reduced copayments, and decision aids all succeeded, to varying degrees, in increasing adherence. However, all reviewed studies targeted a single medication for a single chronic health condition, and none of the reviewed studies &

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included COPD research or addressed polypharmacy for patients with multiple comorbidities. Additional recent studies not included in the review have utilized emerging mobile telephone communication technology, including contacting patients via E-mail [37], text messaging [38–40], interactive voice recognition [41,42], or speech-recognition technology [43,44] to engage and activate patients toward better management of their disease. Once again, these reports embodied a single disease, single medication focus. Consequently, evidence from these studies may not apply to COPD patients who typically have multiple comorbidities with prescriptions for multiple medications. Nonetheless, some of the information from adherence research with other patient populations has potential application for the treatment of COPD. Considerable promise emerges from the collaborative care model, which embraces the concept that chronic disease management will be most successful when care is carefully coordinated between providers and includes education and monitoring of patients. This team-based approach is particularly useful for patients with comorbid conditions and multiple treatments. More than 70 RCTs have shown the effectiveness of collaborative care in improving the care quality and reducing the cost in numerous chronic conditions, most notably in the treatment of the combination of depression accompanied by other chronic illness [45]. Care collaboration often incorporates the utilization of mid-level providers including nurses [46] or pharmacists [47], or, at lower levels of training, patient advocates [48] and patient navigators [49]. These key collaborative care staff work with the physician, but typically can spend more time with patients counseling, educating, and following up in person or by telephone or E-mail. The review of 62 adherence intervention trials [36 ] concluded that the collaborative care approach was particularly effective in improving adherence. The potential for collaborative care in COPD was demonstrated in one study of 138 patients with COPD and depression who were consented and randomized to a usual care control or Personalized Intervention for Depression and COPD (PID-C). The PID-C program was conducted by social worker case managers who counseled patients and promoted active self-management, while also maintaining communication with the patient’s physicians over 26 months. Rates of depression remission were higher, whereas depressive and dyspnea-related symptoms were lower in the PID-C group compared with controls (Fig. 1) [50 ]. A model for COPD collaborative care in the primary care setting has been proposed, with key components including creating a patient-centered medical home linked with other community resources and &&

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Nonadherence in chronic obstructive pulmonary disease Bender

including clinical information systems, decision support, and self-management support (Fig. 2) [51].

(a) Proportion remaining depressed

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PID-C

0.9

TAU

Assessment of recent findings

0.8 0.7 0.6 0.5 0.4 0.3 Discharge

Week 6

Week 14

Week 22

Week 28

(b) PFSDQ-M

165 160 155 150 145 140 135 130 125 120 Discharge

Week 14

Week 28

FIGURE 1. (a) Remission of depression after discharge from rehabilitation hospital and (b) course of dyspnoea-related disability in older adults with major depression and chronic obstructive pulmonary disease (COPD) randomized to personalized intervention for depression and COPD (PID-C) or treatment as usual (TAU). Remission of depression: 17-item Hamilton Rating Scale for Depression  7. PFSDQM, Pulmonary Functional Status and Dyspnea Questionnaire - Modified. Reproduced with permission [50 ]. &

Studies of interventions to improve adherence in COPD patients lag behind other chronic conditions. The paucity of research does not reflect the inadequacy of available treatments. Oxygen supplementation, physical rehabilitation, and medications can greatly improve both longevity and quality of life for patients with COPD. Because of the severity of COPD, advanced age of many patients, and presence of numerous comorbidities, a collaborative care approach will likely provide the most potential for improving overall care, including management of depression and enhancement of adherence. Although briefer interventions have yet to demonstrate efficacy for patients with COPD or other conditions accompanied by polypharmacy, they should not be ignored. The advanced age of many COPD patients may suggest limited usefulness of mobile telephone communication technology, but in 2012 the Pew Research Center reported that 85% of adults in the USA owned a cell phone, with a majority being smart phones capable of internet access [52]. In 2013, the Pew Research Center reported that among adults 65 years of age and older, 43% were present on social networking sites, up from 13% in 2009 [53]. Therefore, resourceful interventions that encompass mobile telephone

Practice change for continuous improvement

Access

Teamwork

Same day appointments Group visits Patient web portal Electronic visits/telecare

Multidisciplinary care team Tasks assigned at highest licensed skill level NP and PA contributions Patient and family activation

Management

Coordination

Case-finding and spirometric diagnosis Practice COPD population registry Preventive services Patient education for self-management

Referrals to pulmonary and rehabilitation PCP provides information to hospital/ER Hospital discharge protocols PCP follow-up after exacerbations

Primary care of COPD

FIGURE 2. A proposed model for COPD collaborative care. COPD, chronic obstructive pulmonary disease; ER, emergency room; NP, nurse practitioner; PA, physician assistant; PCP, primary care physician. Reproduced with permission [51]. 1070-5287 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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communication technology may have particular value when integrated into a multiple-component strategy to improve treatment adherence in COPD patients.

CONCLUSION Despite the fact that 24 million Americans have COPD, it has received considerably less attention in the adherence literature than asthma, diabetes, cardiovascular disease, and other chronic health conditions. The gradual emergence of COPD studies over the last decade has demonstrated that, although COPD therapies can be life sustaining, adherence is remarkably poor. Treatment nonadherence in COPD is documented in the uptake of all therapies, including oxygen supplementation, physical rehabilitation, and medication, and contributes to rising rates of hospitalization, death, and healthcare costs. Although a substantial number of studies have appeared in which adherence interventions have been proposed and studied, only a modicum of COPD adherence interventions have been reported. Lessons learned from the adherence intervention literature have focused on single diseases and ignored multimorbidities, with consequent limited applicability to COPD. The strongest evidence to date suggests that the collaborative care approach can lead to better care and higher patient adherence for complex and comorbid conditions. Such team-based initiatives aim to deliver well synchronized care within teams composed of physicians, nurses, pharmacists, and patient advocates to monitor and support patients in the management of their illness. Although this approach looks promising, comparative effectiveness research is clearly needed to establish the elements of team care that can maximize treatment success and costeffectiveness. Finally, although no evidence has yet established the applicability of brief communication strategies, they remain to be tested with COPD and should not be ruled out. With the rapidly increasing uptake of mobile technology in the USA and around the world, it can be expected that more older patients, including those with COPD, will soon own multifunctionality phones. Adherence may benefit from communication and advice delivered through these devices, along with a larger program of education, monitoring, and support. Acknowledgements None. Conflicts of interest There are no conflicts of interest. 136

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REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. National Heart, Lung and Blood Institute. Global strategy for the diagnosis, management, and prevention of COPD. Bethesda, MD: Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2013. 2. Make B, Dutro M, Paulose-Ram R, et al. Undertreatment of COPD: a retro&& spective analysis of US managed care and Medicare patients. Int J Chron Obstruct Pulmon Dis 2012; 7:1–9. This study identifies COPD that is undertreated because of failure to prescribe maintenance pharmacotherapy in a cohort of over 50 000 patients. 3. Penning-van B, Van Herk-Sukel M, Gale R, et al. Three-year dispensing patterns with long-acting inhaled drugs, in COPD: a database analysis. Respir Med 2011; 105:259–265. 4. Schiller J, Lucas J, Peregoy J. Summary health statistics for U.S. adults: National Health Interview Survey, 2011. National Center for Health Statistics. Vital Health Stat 2012; 10:256; 1–218. 5. Mannino D, HOma D, Akinbami L, et al. Chronic obstructive pulmonary disease surveillance – United States, 1971–2000. MMWR Surveill Summ 2002; 51:1–16. 6. Foster J, Yawn B, Maziar A, et al. Enhancing COPD management in primary care settings. Med Gen Med 2007; 9:24. 7. Balcells E, Anto J, Gea J, et al. Characteristics of patients admitted for the first time for COPD exacerbation. Respir Med 2009; 103:1293–1302. 8. Make B. COPD: developing comprehensive management. Respir Care 2003; 48:1225–1237. 9. Wick J. Long-term oxygen therapy: battling breathlessness. Consult Pharm & 2012; 27:826–830. The author presents strong evidence not only of the life-extending value of oxygen therapy, but also that provider underprescribing and patient nonadherence greatly reduce the potential benefits. 10. Pepin J, Barjhoux C, Deschaux C, et al. Long-term oxygen therapy at home. Compliance with medical prescription and effective use of therapy. ANTADIR Working Group on Oxygen Therapy. Association Nationale de Traitement a Domicile des Insuffisants Respiratories. Chest 1996; 109:1144–1150. 11. Wurtemberger G, Hutter B. Health-related quality of life, psychological adjustment and compliance to treatment in patients on domiciliary liquid oxygen. Monaldi Arch Chest Dis 2000; 55:216–224. 12. Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: Joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest 2007; 131 (5 Suppl.):4S–42S. 13. Jones S, Breen S, Clark A, et al. Pulmonary rehabilitation following hospitalisation for acute exacerbation of COPD: referrals, uptake, and adherence. Thorax 2014; 69:181–182. 14. Hayton C, Clark A, Browne O, et al. Barriers to pulmonary rehabilitation: characteristics that predict patient attendance and adherence. Respir Med 2013; 107:401–407. 15. Yu A, Guerin A, Ponce de Leon D, et al. Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers. J Med Econ 2011; 14:486–496. 16. Makela M, Backer V, Hedegaard M, Larsson K. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD. Respir Med 2013; 107:1481–1490. 17. Cecere L, Slatore C, Ulman J, et al. Adherence to long-acting inhaled && therapies among patients with chronic obstructive pulmonary disease (COPD). J Chronic Obstruct Pulmon Dis 2012; 9:251–258. This retrospective report on 376 veterans with COPD found that only 40% were adherent to inhaled corticosteroids and 54% to long-acting beta agonist. Greater adherence was seen in patients who viewed their physician as an ‘expert’ in COPD diagnosis and management. 18. Toy F, Beaulieu N, McHale J, et al. Treatment of COPD: relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med 2011; 105:435–441. 19. Huetsch J, Uman J, Udris E, Au D. Predictors of adherence to inhaled & medications among Veterans with COPD. J Gen Intern Med 2012; 27:1506–1512. In a cohort of 2730 COPD patients, adherence was poor with maintenance inhaled therapies. Only 19.8% were adherent to inhaled corticosteroids and 30.6% to long-acting beta agonist. 20. Decramer M, Molenberghs G, Liu D, et al. Premature discontinuation during the UPLIFT Study. Respir Med 2011; 105:1523–1530. 21. Simoni-Wastila L, Wei Y, Oian J, et al. Association of chronic obstructive && pulmonary disease maintenance medication adherence with all-cause hospitalization and spending in a Medicare population. Am J Geriatr Pharmacother 2012; 10:201–210. This large database study reported that hospitalization rates and costs were significantly lower in patients who continued with medication in contrast to those who discontinued their medications.

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Nonadherence in chronic obstructive pulmonary disease patients: what do we know and what should we do next?

Although nonadherence research in patients with chronic obstructive pulmonary disease (COPD) lags well behind other diseases, new evidence helps infor...
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