Vol 1, Issue 9


Funding for this newsletter series was provided by
Pulmonary Practice Pearls for Primary Care Physicians 9-part eNewsletter series
Vol 1, Issue 9

Primary care physicians routinely see patients with chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Although treatment guidelines are available, we still need practical information that translates guidelines and other evidence so that we can better diagnose and manage these diseases. Each issue in the Pulmonary Practice Pearls for Primary Care Physicians eNewsletter series focuses on a key topic in the management of COPD or asthma within the context of current national guidelines and clinical practice. Topics are brought to life through the presentation of hypothetical clinical cases, and an emphasis is placed on applying key learnings to clinical practice. Practice tools and links to additional information are featured in each issue.

Series Author

Barbara P. Yawn, MD, MSc, FAAFP
Director of Research
Olmsted Medical Center
Rochester, Minnesota

Dr. Yawn disclosed that she serves on advisory boards for Boehringer Ingelheim GmbH and Novartis Pharmaceuticals Corporation and has received grant support from AstraZeneca; Boehringer Ingelheim GmbH; Merck & Co., Inc.; and Novartis Pharmaceuticals Corporation.

Printer-friendly version

Visit other newsletters in this series

Addressing Adherence in Asthma and COPD

Key Points

Adherence to therapy in asthma and COPD is essential for optimal disease management
A partnership between the health care professionals and the patient is important for optimizing adherence
Nonadherence can be intentional (eg, beliefs/fears about the disease and its treatment or socioeconomic circumstances) or unintentional (eg, forgetfulness or poor inhaler technique)
Effective interventions involve measuring nonadherence, assessing if it is intentional or unintentional, and personalizing strategies to improve adherence

Introduction

Optimal adherence to medical therapy involves the patient and health care professionals (HCPs) working together in a partnership.¹ This partnership is essential because nonadherence is recognized as a common problem.^1-3

Adherence rates for asthma (55%) and chronic obstructive pulmonary disease (COPD; 51%) are lower than those for cardiovascular disease and diabetes (each ~75%).² Adherence in patients with asthma or COPD, assessed by reviewing prescription refill data with refill rates ≥80%, has been reported to be as low as 33%.⁴ In a study of 182 difficult-to-treat asthmatic patients, only 21% were 100% adherent with their combination inhaler therapy.⁵

Adherence to medication can also diminish over time. In a database analysis of >7500 patients with COPD, persistence rates with initial therapy at 1, 2, and 3 years were 25%, 14%, and 8% for long-acting muscarinic antagonists, respectively; 21%, 10%, and 6% for long-acting β-agonists; and 27%, 14%, and 8% for inhaled corticosteroids (ICS)/long-acting β-agonist combinations.⁶

Poor adherence in asthma and COPD has been linked with poorer outcomes, including^3,7:

increased risk of asthma-related death and near-miss cases in adolescents;
increased hospitalizations and mortality;
presence of more severe disease;
poorer quality of life;
reduced productivity.

Guidelines recommend that HCPs monitor adherence.^8-10 This monitoring is particularly important when considering a change of regimen. Indeed, the determination of adherence is an essential step before changing the medication regimen in a patient with suboptimal control.

This newsletter examines key concepts of adherence and highlights tools that can provide support for helping patients take their medicine when and as they should.

Case

John is a 72-year-old man diagnosed with moderate COPD 8 years ago, with a forced expiratory volume in 1 second (FEV₁) of 75% predicted and no exacerbations in the past year. Several years ago, John was also diagnosed with hypertension which has been well maintained on diuretics. He lives alone since his wife's recent death after a prolonged illness. He comes into the office today because his daughter is visiting and thinks his COPD is getting worse. She accompanies John on his clinic visit and complains: "Dad used to work in the garage. Now he seems out of breath just walking around the house." John agrees that he's had more breathlessness in the past few weeks.

He denies any changes in coughing, has no fever, and reports his sputum has remained clear-to-whitish and in small amounts mainly in the morning. Both John and his daughter agree he needs to continue not smoking, "I promised my wife I would never smoke again. And I won't."

You ask John what he thinks is making his breathing worse. John mumbles that he doesn't know.

Note: This is a hypothetical case description for teaching purposes.

Intentional and Unintentional Adherence in Asthma and COPD

The World Health Organization defines adherence as, "the extent to which a person's behavior—taking medication, following a diet, and/or executing lifestyle changes—corresponds with agreed recommendations from a health care professional."¹¹ This definition emphasizes the role of patient behavior and interaction with HCPs and that the behavior can lead to both intentional and unintentional nonadherence.

With intentional nonadherence, patients actively choose to disregard treatment recommendations. A decision not to take a medicine can be based on a range of beliefs and perceptions about the condition and its treatment. In particular, intentional nonadherence can be related to perceptions of illness, such as underestimation of disease severity, doubts about necessity for medication, and concerns about the potential for adverse drug reactions.^9,12 Intentional nonadherence may also be related to inability to access or pay for medications or having to choose which medication to purchase or even choose between medications and food.

Unintentional nonadherence is more passive, involving aspects such as forgetfulness, misunderstanding instructions of the HCP, or physical problems (eg, poor eyesight).^13,14 In COPD or asthma, unintentional nonadherence is often associated with poor inhaler technique, where the patient tries to take the medication, but it is not being delivered to the site—resulting in an outcome similar to not using medication at all (see Issue 4: Teaching Proper Inhaler Techniques to Patients with Asthma or COPD for a full discussion of this topic).

Causes and Factors Contributing to Nonadherence

Factors leading to nonadherence can include patient-related, socioeconomic, therapy, condition, and health care system/HCP-related factors.^15,16

Patient-related factors include lack of understanding of their disease, lack of involvement in the treatment decision-making process, and suboptimal medical literacy. While labeled "patient factors," these may be the result of inadequate health care and education from the medical team. Additionally, the patient's health beliefs and attitudes concerning the effectiveness and side effects of the treatment and level of motivation can affect the degree of medication adherence.^15,16 Social support is also an important mediator of adherence, with cohesive family structures, marriage status, and living conditions being particularly important.² Barriers associated with low socioeconomic status that can affect adherence include high medication costs in relation to income, lack of transportation, poor understanding of medication instructions, and long wait times at the pharmacy.^15,16

Unintentional nonadherence through poor inhaler technique is a problem in both asthma and COPD. Poor inhalation technique for both pressurized metered dose inhalers (pMDIs) and dry-powder inhalers (DPIs) can lead to a decrease of the dose delivered to the lung, as a result, and to poor asthma control.¹⁷ Many patients hospitalized for COPD exacerbations are found to have poor inhaler technique, and a review of adherence in COPD found that only 1 of 10 patients with a pMDI performs all essential steps correctly.^18,19

The concept of unintentional nonadherence can be also thought of as erratic (missing doses because of forgetfulness)¹ or unwitting (when there has been a failure to communicate the dosing schedule clearly). Intelligent nonadherence occurs when the patient deliberately alters or discontinues therapy based on reasoned decision making based on the patient's perceptions of efficacy, side effects, or social or financial circumstances.

Reasons for poor adherence can also be related to difficulties with the medication or other factors not related to medication (Table 1).⁹ Barriers to adherence in asthma and COPD are similar, but there are differences (Table 2).^1,18,20

Incorporating Adherence Strategies Into Clinical Practice

Managing adherence in clinical practice requires the availability of tools to evaluate adherence and simple, effective interventions to address any barriers.

Methods of Assessing Adherence in Asthma and COPD Patients
There are a number of measures to assess adherence that have been used in research, each with advantages and disadvantages (Table 3).¹ Prescription counting and inhaler weighing/dose counting can be inaccurate, because prescriptions can be filled, but not used or taken, and some patients may "dump" doses (discharge the inhaler numerous times until the "required" number of used doses is reached on the dose counter). Electronic dose counters (such as electronic "pill boxes") can be more accurate, but are expensive.

For clinical practice, self-reporting and assessment of refill history are the most feasible and can be used as a basis for discussion with patients. Self reporting has been shown to overestimate adherence vs electronic monitoring.²⁴

Case (continued)

You ask John's daughter to leave during the examination. You check spirometry; his FEV₁ is slightly decreased from 2 years ago at 70% of predicted, but his blood pressure shows deterioration in control at 150/92 mm Hg. Pulse is 78 beats per minute; pulse oximetry is 92%, slightly decreased from 94% a year ago; he is afebrile, and weight is 186 lb (body mass index, 25).

You note that John has lost about 10 lb since his last visit 6 months ago, and he says he has been trying to eat less because he knows his "extra weight" makes walking more difficult. The rest of the examination differs little from previous findings. Lungs are clear, but with a prolonged expiratory phase. A recheck of blood pressure gives a reading of 150/96 mm Hg.

You also screen for depression and find the result is in the "normal" range. You ask John if he is able to take his anticholinergic bronchodilator once daily. John tells you that his wife's illness depleted most of their savings, so he's having trouble paying for his medications and has been skipping some refills. In fact, he is using his inhaler only occasionally to make it last. He does not want his daughter to know—he admits to being embarrassed.

Note: This is a hypothetical case description for teaching purposes.

If the equipment is available, exhaled fractional nitric oxide (FeNO) may be useful in differentiating nonresponsive difficult-to-treat asthma (associated with increased levels of eosinophils in the airway) from nonadherence to ICS.^21,22 Most asthma is associated with increased levels of eosinophils in the airway and can be monitored as nitric oxide present in the exhaled breath is an indicator of the state of the inflammatory processes.²⁵ An alternative is to use a validated adherence questionnaire, such as the Medication Adherence Report Scale for Asthma (MARS-A) or the questionnaire for COPD (MARS-COPD).²⁶ Although such tools are cost-effective and amenable to clinical practice, they do represent one more tool that needs to be used during already over-stressed visit times. These tools, however, might be used when a patient's illness (or any chronic disease) is not well controlled. Both the MARS-A and MARS-COPD tools cover intentional, unintentional, and symptom-driven causes of nonadherence (Figures 1 and 2). Although responses to most items identify intentional or symptom-driven causes, there is also a query on forgetfulness; responses such as "I only use it when I need it" may also uncover unintentional adherence through lack of disease understanding or education.

Adherence assessment requires interaction between the HCPs and the patient. Judgmental approaches are usually unsuccessful in either engaging patients in solving adherence problems or obtaining honest assessments of medications used. Adding comments such as: "I know it must be difficult to take all your medications regularly for many reasons, and I know many patients are unable to take all the medications they should. How are you doing with taking your medications regularly?" and "Have you had to stop any of your medications for any reason?" can help establish the extent of nonadherence without the patient feeling they are being "judged." ¹⁶

Identifying the Type of Nonadherence
Personalizing the approach to nonadherence is essential, and this begins by assessing the type of nonadherence. To identify unintentional nonadherence, ask your patient whether he or she has trouble remembering to take his or her medications and if this happens a lot. You can also ask your patient to review with you the instructions the patient thinks he or she heard for how to use the inhaler. Always ask him or her to demonstrate proper technique. A review of your patient's action plan can be helpful to be sure he or she understands exacerbation management. This review can identify misunderstanding or poor inhaler technique and allow you to develop a personalized intervention to match the type of nonadherence issue identified.¹

For identifying intentional nonadherence, a discussion with your patient about any fears he or she may have about his or her medication or condition can be helpful. Also, it is often helpful to ask if relatives or friends have shared their concerns about the patient's medications. Knowing the concerns may help you revise inaccurate or reinforce correct understanding of the importance of adherence. Always ask about the issues of medication costs. Most patients will appreciate your concern and interest in barriers to adherence.

Approaches to Addressing Nonadherence
Approaches to improving patient adherence in clinical practice fall into 4 categories: technical, behavioral, educational, and multifaceted/complex.²

Technical interventions (eg, changes to dosing and device selection) can include simplifying regimens and using combination inhalers, both of which can improve health outcomes and have cost-benefits for the patient.²
Behavioral interventions include memory aids (eg, notes in a prominent place like the refrigerator, automated email, telephone, or text reminders).
Educational interventions can increase the patient's knowledge of the disease, proper inhaler technique, and of aspects such as self-management; these educational initiatives can be provided through face-to-face, group, or remote (eg, telephone, email, or computer) sessions.²
Multifaceted/complex interventions blend some or all of these techniques to try and maximize effects on adherence.

Examples of specific strategies for intentional and unintentional nonadherence based on these overarching approaches are outlined in Table 4.¹

Helpful Tools for Patient Adherence

The American College of Preventive Medicine has also developed a patient's guide to medication adherence, available at:
http://c.ymcdn.com/sites/www.acpm.org/resource/resmgr/timetools-files/adherencepatientguide.pdf.

The topic of inhaler technique has been addressed in a previous edition of this newsletter series and can be accessed at: (http://newsletter.qhc.com/JFP/JFP_COPDissue4.htm) In addition, the How To Use Inhalers website (http://use-inhalers.com) provides instructions on the use of a wide range of inhalers and may be a useful site for patients or to have available in the office.

Case (continued)

John returns 3 months later, this time alone. He says the social worker to whom you referred him has assisted him with his Medicare plan, instructed him how to use it for his prescriptions, and identified a local pharmacy that accepts his plan. The pharmacy sends him regular notices when his refill is due and provides him with a medication calendar to help remind him to take his medication.

Now that he is using his anticholinergic bronchodilator daily, John reports less breathlessness. His pulse oximetry is up to 95%. He has returned to working periodically in the garage, and you note that with John using the same medication prescribed 2 years ago, but now using it as prescribed, his blood pressure is well controlled again at 124/80 mm Hg.

You review his inhaler technique, congratulate him on his continued nonsmoking, and discuss the importance of taking his medications properly and how pleased you are with his improvement and efforts to improve his health. John wonders how many other people are like him, embarrassed to admit they cannot afford all their medications and don't tell anyone. "Doc, if you had not asked if I was able to take my medicine, it could have been a long time before I told you."

Note: This is a hypothetical case description for teaching purposes.

Conclusions

Nonadherence in asthma and COPD can be intentional (an active decision) or unintentional (a passive process) and can significantly affect clinical outcomes, including disease control and disease-related mortality. Both types of nonadherence can be addressed through effective communication with patients, including establishing a dialogue about personal/social factors that can affect access to medicines. Correct inhalation technique is important to avoid unintentional nonadherence, and regular assessments and re-education can help patients receive the proper dose of their medicine at the right time.

Acknowledgments

I thank Scientific Connexions (Lyndhurst, NJ, USA), for medical writing support funded by AstraZeneca LP (Wilmington, DE, USA).

References

Lareau SC, Yawn BP. Improving adherence with inhaler therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2010;5:401-406.
van Dulmen S, Sluijs E, van Dijk L, de Ridder D, Heerdink R, Bensing J. Patient adherence to medical treatment: a review of reviews. BMC Health Serv Res. 2007;7:55.
Mäkelä MJ, 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.
Rolnick SJ, Pawloski PA, Hedblom BD, Asche SE, Bruzek RJ. Patient characteristics associated with medication adherence. Clin Med Res. 2013;11(2):54-65.
Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009;180(9):817-822.
Penning-van Beest F, van Herk-Sukel M, Gale R, Lammers JW, Herings R. Three-year dispensing patterns with long-acting inhaled drugs in COPD: a database analysis. Respir Med. 2011;105(2):259-265.
van Boven JF, Chavannes NH, van der Molen T, Rutten-van Mölken MP, Postma MJ, Vegter S. Clinical and economic impact of non-adherence in COPD: a systematic review. Respir Med. 2014;108:103-113.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary Disease. Published February 2013. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013_Feb20.pdf. Accessed June 6, 2013.
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Published March 2013. http://www.ginasthma.org/local/uploads/files/GINA_Report_March13.pdf. Accessed August 30, 2013.
National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Full report 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed June 6, 2013.
World Health Organization (WHO). Adherence to long term therapies—evidence for action. Published 2003. http://apps.who.int/medicinedocs/pdf/s4883e/s4883e.pdf. Accessed November 25, 2013.
Capstick TG, Clifton IJ. Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma. Expert Rev Respir Med. 2012;6(1):91-101; quiz 102-103.
Boulet LP, Vervloet D, Magar Y, Foster JM. Adherence: the goal to control asthma. Clin Chest Med. 2012;33(3):405-417.
George J, Kong DC, Stewart K. Adherence to disease management programs in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2007;2(3):253-262.
American College of Preventive Medicine. Medication adherence clinical reference. http://www.acpm.org/?MedAdherTT_ClinRef. Accessed October 9, 2013.
Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86(4):304-314.
Giraud V, Allaert FA. Improved asthma control with breath-actuated pressurized metered dose inhaler (pMDI): the SYSTER survey. Eur Rev Med Pharmacol Sci. 2009;13(5):323-330.
Bourbeau J, Bartlett SJ. Patient adherence in COPD. Thorax. 2008;63(9):831-838.
Restrepo RD, Alvarez MT, Wittnebel LD, et al. Medication adherence issues in patients treated for COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(3):371-384.
Park J, Jackson J, Skinner E, Ranghell K, Saiers J, Cherney B. Impact of an adherence intervention program on medication adherence barriers, asthma control, and productivity/daily activities in patients with asthma. J Asthma. 2010;47(10):1072-1077.
Beck-Ripp J, Griese M, Arenz S, Koring C, Pasqualoni B, Bufler P. Changes of exhaled nitric oxide during steroid treatment of childhood asthma. Eur Respir J. 2002;19(6):1015-1019.
McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012;186(11):1102-1108.
Dweik RA, Boggs PB, Erzurum SC, et al. American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels for Clinical. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-615.
Lindsay JT, Heaney LG. Nonadherence in difficult asthma - facts, myths, and a time to act. Patient Prefer Adherence. 2013;7:329-336.
Kobayashi, Y. The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation. J Leukoc Biol. 2010;88(6):1157-1162.
Cohen JL, Mann DM, Wisnivesky JP, et al. Assessing the validity of self-reported medication adherence among inner-city asthmatic adults: the Medication Adherence Report Scale for Asthma. Ann Allergy Asthma Immunol. 2009;103(4):325-331.

Table 1. Adherence Factors: Medication or Nonmedication Causes⁹

Causes Related to Medication	Causes Not Related to Medication
Difficulties using the inhaler device	Dissatisfaction with HCP team
Dosing regimens are complex or difficult to follow	Unexpressed fears or anger about the disease or treatment
Side effects, perceived or real	Inappropriate expectations
Medication cost	Forgetfulness or complacency
Dislike of medication	Cultural and/or religious issues
Pharmacy location inconvenient	Poor supervision, training, or follow-up for asthma self-care
Misunderstanding or lack of instruction on proper inhaler use	Underestimation of severity of disease/effect of nonadherence

Abbreviations: HCP, health care professional.

Table 2. Barriers to Adherence in Asthma and COPD^1,18,20

Asthma	COPD
Patient's lack of appreciation of the need for treatment and/or the consequences of nonadherence	Cognitive decline (a factor associated with COPD)
Low perceived disease severity	Psychiatric comorbidity (up to 40% of COPD patients have clinical depression)¹⁸
Young age	Advanced age and limited visual acuity and manual dexterity (ability to use inhaler correctly)
Lack of confidence in the HCP or the medication	Ineffective communication with HCP
Lack of motivation to change behavior	Limited access to self-management support programs
Limited income	Financial stress
	Polypharmacy, regimen complexity
	Continuity of care issues, such as lack of primary care, or a medical home to direct care

Abbreviations: COPD, chronic obstructive pulmonary disease; HCP, health care professional.

Table 3. Advantages and Disadvantages of Different Adherence Measures¹

Assessment Measures	Advantages	Disadvantages
Clinician estimates	Easy to obtain	Unreliable
Patient self-reports	Easy to obtain	Unreliable
Pill counts/weighing	Easy to obtain	Overestimates use
Pharmacy records	Confirms prescription filling	Incomplete, biased estimates
Biological measures	Confirms ingestion	Expensive, invasive, insensitive to inhaled drugs, affected by pharmacokinetics and polypharmacy
Electronic monitoring	Patterns of use, ingestion	Expensive, limited availability and use, malfunctions
FeNO	Easy to obtain Can differentiate difficult-to-treat asthma from nonadherence^21,22	Requires appropriate equipment Not useful in asthma patients for whom underlying inflammation does not increase FeNO levels²³

Data from Lareau and Yawn.¹

Abbreviation: FeNO, fractional exhaled nitric oxide.

Table 4. Matching Interventions to the Type of Nonadherence¹

Type of Nonadherence	Strategies for Intervention
Unintentional (may be related to cognition)	Simplify and tailor regimen Implement behavioral strategies such as cueing (eg, storing medication next to toothbrush), reminders, and reinforcement Support with monitoring from others
Unintentional (may be related to communication failure)	Review of adherence behavior Written or visual medication plans Patient education in disease management
Intentional (patient choice)	Patient education and counseling Negotiate therapy Link therapy with personal goals

Abbreviations: HCP, health care professional.

Figure 1. Medication Adherence Report Scale for Asthma (MARS-A) Questionnaire

Copyright of MARS-A and all its variants is owned by the originator Robert Horne, PhD, and permission to use it should be obtained by requests to r.horne@ucl.ac.uk.

Figure 2. Medication Adherence Report Scale for COPD (MARS-COPD) Questionnaire.

Copyright of MARS-COPD and all its variants is owned by the originator Robert Horne, PhD, and permission to use it should be obtained by requests to r.horne@ucl.ac.uk.