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Optimizing Adherence to Improve Clinical Outcomes in Patients with Chronic Obstructive Pulmonary Disease.


Chronic obstructive pulmonary disease (COPD), a common condition characterized by persistent and progressive airflow limitation, is a major cause of morbidity and mortality worldwide. (1,2) However, COPD can be treated effectively if diagnosed early. A multicomponent approach, including oral and inhaled medications (eg, corticosteroids, bronchodilators, or combination therapy) and nonpharmacologic interventions (eg, pulmonary rehabilitation, lifestyle advice, and self-management techniques), alleviates symptoms, slows disease progression, reduces the frequency and length of exacerbations and hospital admissions, and improves the quality of life. (3,4) Main treatment goals for stable COPD are reduction of symptoms and future risk of exacerbations, and treatment goals for exacerbations are to minimize the negative effects of the current exacerbation and to prevent future exacerbations. (1) Poor medication adherence among COPD patients is one of the key factors preventing patients from reaching treatment goals. (5,6) Major consequences of poor medication adherence in COPD patients include poor disease control and increased number of hospitalizations and deaths due to acute exacerbations. (7) Herein, we review ways in which primary care providers (PCPs) can help patients meet treatment goals, including making use of technological advancements in inhaler design and monitoring, which can improve patient adherence.


Despite the availability of effective pharmacologic treatments and comprehensive treatment recommendations such as those from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), (1) the prevalence of inadequately controlled COPD (assessed by control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and quality of life) (8) is high, largely because of inadequate medication adherence. (9) Medication adherence among COPD patients is suboptimal and lower than that among patients with other chronic diseases such as diabetes, heart failure, and hyperlipidemia. (10) In a study involving more than 14,000 COPD patients, only 21% were adherent to maintenance COPD medications. (11) Further, a positive association was observed between nonadherence to maintenance COPD medications and nonadherence to medications for other chronic diseases, implying that the need to take medications for comorbid conditions does not negatively affect adherence to COPD medications.

Patient-related factors contributing to medication nonadherence can be grouped into 2 distinct patterns of behaviors: intentional and unintentional. Intentional non-adherence, which is a voluntary discontinuation or deviation from the prescribed medication plan, often stems from patients' health beliefs and incorrect understanding of the disease course and treatment goals. (3) Unintentional non-adherence results from factors outside patients' control, most commonly complex medication regimens and polypharmacy. (12) Patients with COPD are generally older adults who require medications for various comorbidities. (13) Additionally, factors such as cognitive impairment, (14) low health literacy, (15) poor eyesight, physical disability, and musculoskeletal issues/lack of dexterity (3) can lead to inhaler incompetence and, thus, poor adherence. Moreover, difficulty in engaging with PCPs, daily fluctuations in symptoms, overuse of rescue medications, use of multiple inhalers, poor inhaler technique, and poor understanding of COPD also contribute to suboptimal adherence. (3,16) Finally, age-related pulmonary changes and decreased lung function (17) may impact adherence, particularly with inhalers that require deep inhalation for optimal medication deposition in the lungs (eg, dry powder inhalers [DPIs]). Importantly, some of these factors, such as overuse or underuse and poor inhaler technique, are modifiable.

Medication- and inhaler-related factors contributing to medication nonadherence include adverse effects, dosing regimens that require multiple drugs or doses, and routes of administration. (18-20) In general, the longer and more complicated the regimen, the greater the likelihood of nonadherence; moreover, patients prefer once-daily therapies to those requiring multiple doses a day. (18) Among COPD patients, adherence is higher for oral than for inhaled medications of the same class (eg, corticosteroids or [beta]-agonists). Other factors contributing to poor COPD medication adherence include health system factors such as medication reimbursements and patient-PCP relationship and socioeconomic factors such as family/caregiver support, income, transportation, (21) and inhaler training. (22) According to hierarchical clustering, COPD patients usually fall into 1 of 3 distinct clusters of adherence: low inhaler use and high error rates, high inhaler use and high error rates, or good adherence, with only a little more than one-third of patients belonging to the good adherence cluster. (17)


As mentioned before, COPD patients overuse and underuse medications for various reasons. (23) Approximately half of COPD patients report overuse of prescribed medications during exacerbations. (23) Underuse of COPD medications can be sporadic (eg, occasionally forgetting a dose) or systemic (eg, taking the medication once instead of twice a day over a long period of time). (24) The need to use multiple inhalers and switching treatments/inhalers often leads to confusion and consequent overuse, underuse, or both. (9,25,26) Development of dual, fixed-dose combination bronchodilators and potential triple dose combination inhalers (long-acting [[beta].sub.2]-agonist/longacting muscarinic antagonist/inhaled corticosteroid [LABA/ LAMA/ICS]) might improve adherence among patients who require multiple medications. (27,28) Inhaler design potentially contributes to overuse and underuse, as well. Overuse is most prominent for inhalers without a dose counter, inhalers for which a dose can be loaded without actual inhalation, and inhalers lacking feedback on correct inhalation. (29)


Development of safe and efficacious inhalation therapy with targeted delivery of medication directly to the site of action depends not only on a pharmacologically active molecule but also a well-designed formulation and inhalation device. Common types of traditional inhalers for COPD medications include pressurized metered dose inhalers (MDIs), including chlorofluorocarbon- (nearly obsolete) and hydrofluoroalkane (HFA)-driven MDIs that are breath activated and may require spacer devices, and DPIs, which are also breath activated (30) (table). Patient characteristics that should be considered by PCPs before prescribing an inhaled COPD medication include coordination abilities, comfort level with the inhaler, and prior experience with inhalers. (31)

Poor inhaler technique is a common issue with traditional COPD inhalers, (32,33) and improper use of an inhaler is associated with an increased risk of emergency room (ER) visits, hospitalizations, and the need for corticosteroid treatment. (32) Common patient errors related to inhaler technique include failing to exhale before actuation, prematurely stopping inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and lack of deep inhalation or breath holding after inhalation. (33) While many of these factors can be corrected with proper training, some cannot. Inhaler technique can be improved with adequate training and reinforcement. However, it can be challenging for PCPs in the current healthcare environment to commit to a continual and time-consuming process of training patients for correct inhaler technique. (34) Nurses, pharmacists, and respiratory therapists can potentially contribute to the improvement of inhaler technique in patients with COPD.

Performance of traditional inhalers is limited by the need for good coordination between patient inspiration and inhaler activation (MDIs) or sufficient inspiratory flow (DPIs). (33,35) Inability to maintain slow inspiratory flow rate and breath holding during MDI use may result in reduced lung deposition of the medication. Similarly, failure to forcefully and deeply inhale during DPI use results in higher medication deposition in the mouth and throat and poor bioavailability. Further, patients with severe airflow limitation may be unable to meet the peak inhalation flow rate required for correct inhaler use. (36) About 31% (28%-35%) of patients with chronic respiratory diseases, including COPD and asthma, cannot use their inhalers (either MDI or DPI) well enough to benefit from the prescribed medication. (37) With traditional inhalers, poor technique reduces the lung deposition of the medication (38) and consequently its efficacy. (33)

A relatively new inhaler, Respimat, which circumvents some of the patient-related limitations of traditional inhalers, is available. Respimat is a hand-held, propellent-free, slowmist inhaler (SMI) that generates a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible energy supply. (39) This inhaler provides a slower moving aerosol (0.8 m/s vs. 2-8.4 m/s) with longer duration (1.5 s vs. 0.15-0.36 s) than MDIs (table). (39,40) In multiple studies, Respimat significantly improved lung deposition of drug aerosols compared to HFA-MDIs and DPIs, even in patients with poor inhaler technique. (39,41-43) As with other types of inhalers, PCPs should be familiar with proper Respimat technique to ensure appropriate patient training. Of note, inserting the cartridge into the inhaler until it clicks into place can be a challenge for certain patients, such as the elderly or patients with disabilities. To avoid this potential limitation, pharmacists can be instructed to preload the cartridge. Elderly patients with poor hand-lung coordination can be encouraged to use a spacer or a valved holding chamber to ensure correct use.44 Importantly, patients consider spacers easy to use and maintain, and ease of use markedly influences patients' acceptance of the inhaler. (45) Moreover, previous experience with DPIs, MDIs, or both did not influence patient preference and acceptability. (46) Interestingly, patient satisfaction with their inhaler significantly correlated with treatment adherence in at least one study. (47)


Different strategies involving patients, PCPs, and technology can be employed to help improve medication adherence and clinical outcomes (figure). Acknowledging the disparity in treatment goals between physicians and patients is important to overall patient care for therapeutic decision-making as well as improving physicianpatient communication. Patients generally value more tangible and integrated concepts such as fast onset of action and decreased mortality over "text book" treatment goals, including prevention and treatment of exacerbations and improvement of health status, propagated by physicians. (48) Patients have personal beliefs about their illness and treatment, which can be grouped into 2 categories: patient perceptions of personal need for treatment (necessity beliefs) and patient concerns about potential adverse consequences of the disease state and the related treatment. (49) Addressing the "necessity-concern framework" of individual patients helps PCPs understand patients' treatment goals better, enhances engagement of PCPs with patients in shared decision-making related to the choice of treatments, encourages self-management, and supports optimal adherence to medications. (49,50) Authors of recent systematic reviews concluded that self-management programs reduce the probability of COPD-related hospital admissions and overall healthcare utilization, especially when used with other components of the chronic care model. (51,52) Key topics for discussion with patients are disease education, the gains in quality of life and lessening symptom burden that can be achieved with cooperation and following the action plan, and the benefits of referral to pulmonary rehabilitation. (53,54) Understanding and addressing barriers to adherence and proper inhaler techniques are important. Questions to consider include whether or not patients are using the correct inhaler technique, have adequate dexterity to use the inhaler, or have sufficient inspiratory flow rate to achieve adequate lung deposition of the medication (for DPIs), as well as whether or not the medication and inhaler are acceptable to the patient. (55)

Inhaler technique training, which is often inadequate and not repeated at follow-up appointments, (33) can make patients uncomfortable using the inhaler and may result in nonadherence or discontinuation. In a survey of US patients with COPD, only 22% reported complete confidence in using inhalers. (56) When compared to patients with low confidence in using inhalers, those with greater confidence reported higher adherence rates and better COPD-related health status. (56) Choosing an inhaler suitable to patients' needs and abilities can enhance patients' confidence and improve long-term adherence. (56) Teaching proper technique with each new medication and assessing the technique at followup appointments, with retraining if necessary, is critical to maintaining optimal adherence. Several options for patient education are available, including physical demonstrations, audio-visual media, 'YouTube' videos, and graphical depictions of proper inhaler technique. Inhaler training via physical demonstration or audio-visual media has been shown to improve inhaler technique. (57-59) The "teach-back" strategy, where patients are taught how to use the inhaler and asked to explain or demonstrate proper technique back to the PCP, can be employed to ensure that patients understand and execute the correct technique. (60) In multiple studies with different types of inhalers, this strategy significantly improved the proportion of correct inhaler users. (60) While written literature is not as effective as teaching patients directly, a leaflet containing graphic figures depicting proper inhaler technique is a better option than purely written instructions. (61) However, educational interventions only improve inhaler technique effectively over the short term; periodical reinforcement and longer patient follow-up are recommended for long-term success. (57)

In addition to regular inhaler technique training, regular monitoring of medication adherence is important to achieve optimal outcomes. To this end, more efficient monitoring is possible with recent technological advancements, including spacer data loggers for MDIs, (62) the test of adherence to inhalers (TAI) tool, (63) dose counter-equipped inhalers to help patients track medication use, (64,65) pharmacy refill information, (66) audio-based systems, (17,67) and electronic inhaler reminders. (68) TAI, a 12-item questionnaire, is a validated tool that is reliable and cost-effective in clinical practice, though it tends to underestimate adherence to inhalers compared to other sensitive methods. (69) Dose counter-equipped inhalers help patients avoid overuse of rescue medications. (64) By ensuring that patients do not use rescue medication beyond the recommended number of actuations, dose counters can reduce dose-related morbidity and mortality, and potentially improve the quality of life. Use of periodic reminders and adherence feedback improves patients' attitudes toward adherence and confidence in self-management of their disease. (68) In a recent study, nurse-guided training based on the repeated bio-feedback generated by an electronic device significantly improved inhaler adherence. (70) Moreover, pharmacies usually have patients' detailed medication and dispensing history and pharmacists can use that information to identify potential nonadherent patients in need of support. (71) Pharmacists can also play a key role by providing advice and education on dosage, inhaler technique, treatment expectations, and the importance of adherence, thereby supporting self-management, including recognition and treatment of COPD exacerbations. (72) In multiple studies, community pharmacists' interventions had a positive impact on improving patients' inhalation technique and adherence to inhaled medications through a comprehensive COPD support service. (61) The ideal role of community pharmacists in COPD management deserves further study, as the potential benefits to patients are quite positive.
FIGURE Strategies to improve medication adherence
in patients with COPD



* Disease education

* Selection of appropriate inhalers
suitable for patients' needs

* Adequate inhaler
training and


* Availability of multimedication,

* Use of SMIs for better
lung deposition

* Better monitoring
of adherence


* Better self-management
of COPD and related comorbidities

* Regular consultations with HCPs
to establish common treatment

Abbreviations: COPD, chronic obstructive pulmonary
disease; HCP, health care provider; PCP,
primary care provider; SMI, slow-mist inhaler.

While the need for inhaler technique assessment, education, and consolidation is acknowledged, more research is required to identify the optimal frequency of these interventions as preemptive measures against technique deterioration in patients. (61) Furthermore, ongoing evaluation of the impact of using specific, validated electronic monitoring devices on inhaled medication adherence in patients with chronic obstructive lung diseases such as asthma and COPD will improve our understanding of medication adherence in respiratory diseases overall. One such sophisticated method measures adherence using electronic data capture devices, which save the date and time of each inhaler actuation and transfer the data daily via a wireless connection to a web-based database. (73) COPD patients and PCPs can work together to effectively use these types of technological advances to attain optimal medication adherence.


Adherence to COPD medications is multifactorial, and poor adherence is a major barrier to COPD patients achieving their treatment goals. Patient education and empowerment to enable effective self-management of their COPD symptoms is essential. Moreover, because inhaler technique is an important contributor to poor adherence, physicians, nurses, physiotherapists, respiratory technicians, and pharmacists can make meaningful improvements in COPD outcomes by demonstrating and reinforcing proper inhaler technique. Furthermore, technological advances may soon allow adherence to be monitored more efficiently. The emergence of dual, fixed-dose therapies should help reduce administration complexity when multiple medications are required. In summary, PCPs can play key roles in improving COPD medication adherence and helping patients with COPD achieve treatment goals by going beyond conventional educational approaches and empowering patients with necessary self-management skills.


Dr. Garvey discloses that she is on the speakers' bureau for Boehringer Ingelheim.

Dr. Kaplan discloses that he is on the advisory board and speakers' bureau for Boehringer Ingelheim, AstraZeneca, Purdue Pharma, and Novartis. He is on the advisory board for GlaxoSmithKline and Mylan, is a speaker for Grifols, and advisor on Johnson & Johnson's smoking cessation website design outside of this submitted work.


The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors received no direct compensation related to the development of the manuscript. Writing, editorial support, and formatting assistance was provided by Saurabh Gagangras, PhD, and Maribeth Bogush, PhD, of Cactus Communications, which was contracted and compensated by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.


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Chris Garvey, MSN, MPA, FNP, Pulmonary Rehabilitation and Sleep Disorders, University of California, San Francisco, CA

Alan G. Kaplan, MD, CCFP(EM), FCFP, Department of Family and Community Medicine, University of Toronto, Ontario, Canada
TABLE Important characteristics, advantages, and
limitations of inhalers used in the treatment of
COPD (38,55 74)

Type of inhaler

Characteristics      MDI

Formulation          Drug suspended or
                     dissolved in propellant
                     (with surfactant and

Metering system      Metering valve and

Mean velocity of     2-8.4 m/s
aerosol cloud

The spray duration   0.15-0.36 s

Advantages           Reproducible dosing
                     No contamination risk
                     Independent of
                     inspiratory flow

Limitations          Requires coordination
                     between actuation and

                     High oropharyngeal
                     deposition Cold Freon


                     Need for spacers in
                     certain populations

Characteristics      DPI

Formulation          Drug blended in lactose,
                     drug alone, or drug/
                     excipient particles

Metering system      Capsules, blisters,
                     multidose blister packs
                     or reservoirs

Mean velocity of     --
aerosol cloud

The spray duration   --

Advantages           Breath-actuated
                     (coordination not

Limitations          Inspiratory flow-
                     dependent Poor dose


Characteristics      SMI (Respimat)

Formulation          Aqueous solution or

Metering system      Unit dose blisters or

Mean velocity of     0.8 m/s
aerosol cloud

The spray duration   -1.2 s

Advantages           Slow velocity aerosol
                     Longer duration
                     Does not require coordination
                     High lung deposition
Limitations          Dose loading into the inhaler

Abbreviations: COPD, chronic obstructive pulmonary disease; DPI,
dry-powder inhaler; MDI, pressurized metered-dose inhaler: m/s.
meter per second; s, second; SMI, slow-mist inhaler.
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Author:Garvey, Chris; Kaplan, Alan G.
Publication:Journal of Family Practice
Article Type:Report
Date:Oct 1, 2018
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