Write a 3 page article review not including a title page abstract and refernce page. Cannot use personal pronouns.
Determinants of Patient Adherence to an Aerosol Regimen Joseph L Rau PhD RRT FAARC
Introduction
Compliance or Adherence?
Defining Adherence
Types of Nonadherence
Measurement of Adherence With Aerosol Regimens General Studies of Adherence With Aerosol Therapy Correct Aerosol Device Technique
Complexity of Inhalation Regimen
Dosing Frequency
Combination Formulations of Inhaled Drugs
Route of Administration: Oral vs Aerosol
Type of Inhaled Medication: Inhaled Corticosteroids vs 2 Agonists Patient Awareness of Monitoring and Effect of Feedback on Monitoring Patient Beliefs, Sociocultural, and Psychological Factors
Summary: Improving Adherence With Aerosol Therapy
Patient adherence with prescribed inhaled therapy is related to morbidity and mortality. The terms “compliance” and “adherence” are used in the literature to describe agreement between prescribed medication and patient practice, with “adherence” implying active patient participation. Patient adherence with inhaled medication can be perfect, good, adequate, poor, or nonexistent, although criteria for such levels are not standardized and may vary from one study to another. Generally, nonadherence can be classified into unintentional (not understood) or intentional (understood but not followed). Failing to understand correct use of an inhaler exemplifies unintentional nonadher- ence, while refusing to take medication for fear of adverse effects constitutes intentional nonad- herence. There are various measures of adherence, including biochemical monitoring of subjects, electronic or mechanical device monitors, direct observation of patients, medical/pharmacy records, counting remaining doses, clinician judgment, and patient self-report or diaries. The methods cited are in order of more to less objective, although even electronic monitoring can be prone to patient deception. Adherence is notoriously higher when determined by patient self-report, compared to electronic monitors. A general lack of adherence with inhaled medications has been documented in studies, and adherence declines over time, even with return clinic visits. Lack of correct aerosol- device use is a particular type of nonadherence, and clinician knowledge of correct use has been shown to be imperfect. Other factors related to patient adherence include the complexity of the inhalation regimen (dosing frequency, number of drugs), route of administration (oral vs inhaled), type of inhaled agent (corticosteroid adherence is worse than with short-acting 2 agonists), patient awareness of monitoring, as well as a variety of patient beliefs and sociocultural and psychological factors. Good communication skills among clinicians and patient education about inhaled medica- tions are central to improving adherence. Key words: compliance, adherence, aerosol, metered-dose inhaler, MDI, dry powder inhaler, DPI. [Respir Care 2005;50(10):1346 –1356. © 2005 Daedalus En- terprises]
DETERMINANTS OF PATIENT ADHERENCE TO AN AEROSOL REGIMEN
Introduction
The importance of patient adherence to prescribed med- ication therapy lies in the documented relationship of poor adherence to increased morbidity and even mortality.1–3 Bauman et al found significantly worse asthma morbidity among children when they or their caregivers scored high on measures of nonadherence with therapy.2 Williams et al found that adherence to inhaled corticosteroid therapy, based on medical/pharmacy records, was approximately 50% in a large group of asthmatics, and negatively corre- lated with the number of emergency department visits.3 They also reported that each 25% increase in the propor- tion of time without inhaled corticosteroid medication re- sulted in a doubling of the rate of asthma-related hospi- talization. Milgrom et al found that median compliance with inhaled corticosteroids among asthmatic children was 13.7% for those having exacerbations and 68.2% for those who did not.4
Compliance or Adherence?
There are 2 terms used in the literature to refer to how well a patient follows a prescribed regimen of drug dosing or any prescribed therapy: adherence and compliance. The latter term seems to be favored more recently in the liter- ature, and this may be because of differences in the exact meaning of the 2 terms. While both terms describe agree- ment between a patient’s actions and prescribed therapy, “compliance” has the connotation of giving in to a request or demand; “adherence” on the other hand connotes stay- ing attached or staying firm in supporting or approving, based on definitions in a standard Webster’s dictionary.5 “Adherence” thereby seems to imply a patient’s choice to follow prescribed therapy, while “compliance” implies a certain passivity to another’s request. In fact a synonym for “compliant” in one dictionary consulted is “obedient.”5 In a 1995 publication, Tashkin defined compliance “sim- ply as following the instructions of the health-care provid- er.”6 As a result, “compliance” conjures a view of the patient as a passive participant following orders. In con- trast, “adherence” describes an active patient who is an empowered partner in his or her care.7 Aside from political correctness, it seems to make sense to have a patient who
Joseph L Rau PhD RRT FAARC is Professor Emeritus, Cardiopulmo- nary Care Sciences, Georgia State University, Atlanta, Georgia.
Joseph L Rau PhD RRT FAARC presented a version of this article at the 36th RESPIRATORY CARE Journal Conference, Metered-Dose Inhalers and Dry Powder Inhalers in Aerosol Therapy, held April 29 through May 1, 2005, in Los Cabos, Mexico.
Correspondence: Joseph L Rau PhD RRT FAARC, 2734 Livsey Trail, Tucker GA 30084. E-mail: [email protected].
actively desires to work with a health-care provider in- stead of one who follows directions with little interest in taking responsibility for the process. In an editorial ac- companying a study on patient compliance, Mellins and associates commented that “there is a growing recognition that to improve significantly the way in which they use medicines and otherwise manage disease, patients must be actively involved in the process of determining the thera- peutic plan.”8 Throughout this review, the terms “compli- ance” and “adherence” will correspond to those used in the particular studies described. Otherwise the term “adher- ence” will be used to describe agreement between pre- scription and practice.
Defining Adherence
Rand and Wise define “adherence” as “the degree to which patient behaviors coincide with the clinical recom- mendations of health-care providers.”9 They note that this definition is too broad and call for adherence to be situ- ationally defined, with good adherence explicitly delin- eated. They also note that there is no gold standard for “good” or “acceptable” adherence. For example, adequate adherence may describe asthma-clinic patients who use 40% of the prescribed medication and are symptom-free and controlled. However, a subject in a research study who takes 60% of prescribed doses may be considered nonad- herent.9 An example of the type of definition of adherence called for by Rand and Wise can be found in the context of a study by Tashkin et al, who used metered-dose inhaler (MDI) canister-weight criteria to define compliance rat- ings.10 For example, using calculated grams of medication per day, 0.45 g/d might be “over-compliance,” 0.35– 0.45 g/d “good compliance,” and so forth. Such a method gives a specific criterion (g/d) to rate degrees of compli- ance.
Types of Nonadherence
Nonadherence with therapy takes multiple forms, rang- ing from incomplete to total nonuse. The various types of nonadherence with prescribed therapy can be broadly cat- egorized into 2 types: unintentional (not understood), and intentional (understood but not followed).11 Table 1 gives a more detailed outline of potential factors that can pre- dispose to these types of nonadherence.11–13 Unintentional nonadherence includes misunderstanding the prescribed regimen, incorrect aerosol device technique, or language barriers. Intentional nonadherence can be caused by pa- tient beliefs (eg, that drug therapy is ineffective, unneces- sary, or dangerous), forgetfulness, stress, busy lifestyle, or complex, demanding aerosol regimens. Of the two, unin- tentional nonadherence may be easier to remedy.
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Table 1.
General Types of Nonadherence to Prescribed Aerosol Therapy and Potential Factors That Can Predispose to Each Type*
actual inhalation of medication by patients. With the neb- ulizer chronolog, medication can be sprayed into the air, or the switch flicked manually. The Electronic Diskhaler records both blister perforation and airflow, which gives some indication that inhalation occurred following DPI loading.20
Tashkin et al investigated adherence with aerosol ther- apy, using the nebulizer chronolog, in comparison with canister weighing and patient self-report with a group of patients with chronic obstructive pulmonary disease (COPD).10 Their study found that both canister weights and self-report overestimated adherence with prescribed therapy among patients who were not informed of the nebulizer chronolog’s recording ability (Fig. 1).
Rand et al also used the nebulizer chronolog to compare adherence to a 3-times-daily use of 2 MDI inhalations of ipratropium or placebo by patient self-report at follow-up and canister-weight-change over a 4-month period.15 Both self-report and canister-weighing overestimated correct in- haler use, compared to nebulizer chronolog measures. Neb- ulizer chronolog data showed that only 15% of the sub- jects used the MDI an average of 2.5 or more times per day, as prescribed. In contrast, 73% of subjects self-re- ported correct daily inhaler use. Canister-weighing over- estimated correct inhaler use as prescribed for 61% of participants, correctly estimated use for 39% (although not always as prescribed), and underestimated use for 0%. Nebulizer chronolog data also showed that 14% of sub- jects actuated their inhalers more than 100 times in a 3-hour interval, often before clinic visits, a practice known as “dumping,” or the “parking lot phenomenon.”9,15 Canister weighing cannot differentiate correct use from wasted med- ication.
Milgrom et al also looked at patient compliance to both agonists and inhaled corticosteroids, using the nebulizer chronolog versus patient diaries.4 Figure 2 shows a sum- mary of the compliance data for both inhaled medications over 13 weeks. Diary reports claimed a median use of agonists of 78.2% of prescribed dose, and a steroid use of 95.4%. Data from the nebulizer chronolog giving time- corrected compliance (doses taken within the correct time window) showed 48% for agonists and 32% for inhaled steroids. Only 2 agonists taken on a fixed schedule (2 or 3 times a day or every 6 hours) were included in the analysis. Similar results for electronic monitors in com- parison with patient reports, canister weight, and remain- ing dose counts have been reported in other studies.18,22–23 A study by Burrows et al showed that patient self-report- ing also overestimated adherence when compared to data from pharmacy-dispensing records for nebulized dornase alfa in cystic fibrosis patients.24 Based on the comparisons cited, it is relevant to note that results of different studies can depend at least partly on which measure of aerosol adherence is employed.
DETERMINANTS OF PATIENT ADHERENCE TO AN AEROSOL REGIMEN
Unintentional: Patient does not understand therapy correctly Misunderstanding prescribed drug regimen (poor doctor-patient
communication)12
Incorrect aerosol device technique Language barriers
Intentional: Patient understands therapy but does not adhere correctly Patient beliefs
I do not really require regular medication
I am not really sick
I gain attention from parents, am kept at home (children) The medication is too expensive
I have concern about adverse effects
I do not perceive effect from the medication
Forgetfulness
Stress and busy lifestyle
Complex, demanding aerosol regimens Psychological factors (eg, depression)13
*Two general categories of nonadherence are based on Reference 11.
Measurement of Adherence With Aerosol Regimens
There are a number of methods for measuring congru- ence of patient behavior with prescribed aerosol therapy, which are listed in Table 2.9,11 These methods differ sub- stantially in the degree of accuracy and objectivity with which patient adherence can be determined. In general, direct measures of patient behavior, such as direct obser- vation or electronic inhaler monitors, give more accurate, valid measures than indirect methods such as patient dia- ries, self-report, or clinician’s judgment.9,11,14 There are several electronic monitors that have been reported in the literature for use with MDIs or dry powder inhalers (DPIs).
The “nebulizer chronolog” device and the “Doser Clin- ical Trials” device have been used with MDIs.15–17 The nebulizer chronolog is a microprocessor device built into the sleeve housing an MDI; it records the date and time of each inhaler actuation, by activation of a microswitch.4,15 The Doser Clinical Trials device is described as an inex- pensive pressure-activated device, also used with MDIs.17 It is a round, flat device secured to the top of the MDI canister, and it records only the number of daily uses over a period of 45 days.18 A similar MDI electromechanical counter was reported by Yeung et al.19 The Electronic Diskhaler allows monitoring of the Diskhaler DPI, by re- cording drug blister piercing and airflow through the in- haler.20 A similar device, the Turbohaler Inhalation Com- puter has been used with the Turbohaler DPI, known as the Turbuhaler in the United States.13 An electronic adherence monitor has also been reported for the Diskus DPI.21 It should be noted that not all electronic monitors guarantee
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Table 2. Methods of Measuring Adherence With Prescribed Aerosol Drug Therapy, Based On Measures Noted in the Literature*
Method Biochemical measures
Medication/device monitors
Observation of device technique
Medical/pharmacy records
Monitoring remaining dose counts or medication
Clinical judgment of provider Patient self-report
Example
Analysis of blood, urine, or secretions to measure drug level
Electronic monitor records date and time of inhaler use
Direct review of patient performance with aerosol device, usually periodic
Retrospective review of patient records or refills
MDI canister weighing
DPI doses left
SVN doses or solution packages
left
Global judgment of health-care provider during clinic visits
Periodic recall survey or interview Patient diary
Strengths
Accurate Objective
Accurate Objective
Accurate with training of observer
Simple Objectively based
Objective
Relatively simple to obtain
Simple Objective Low cost
Quick Low cost
Fast for health-care provider Low cost
Ease of use
Limitations
Expensive
Intrusive
Limited drug tests
Limited to recent drug therapy
Cannot tell if patient actually received dose
Expensive
Possible alteration of patient habits?
Limited to time of observation Limited to device-use only, not
dose schedule Requires staff time
Time required to obtain patient data Limited to detecting nonrefills
No information on correct patient
use or scheduling of drug with refills
Possible patient deceit by wasting doses
No information on actual dosing schedule
Requires staff time
Low validity and reliability14
Vulnerable to patient error or deceit15
*The methods are listed in order of relative accuracy, from greater to less. (Adapted from References 9 and 11.) MDI metered-dose inhaler
DPI dry powder inhaler
SVN small-volume nebulizer
General Studies of Adherence With Aerosol Therapy
The general lack of adherence with prescribed aerosol therapy has been documented in a number of studies,
Fig. 1. Percentage of adherence with prescribed metered-dose inhaler (MDI) medication among patients with chronic obstructive pulmonary disease, determined with 3 methods of monitoring: neb- ulizer chronolog (electronic MDI monitor), MDI canister weight change, and patient self-report. (Based on data from Reference 10.)
including patients with asthma,25–27 as well as COPD.15,28 –29 Rand and associates documented that COPD patients had poor adherence with prescribed 3-times-daily MDI therapy, as measured with the neb- ulizer chronolog.15 Fewer than 20% of 70 patients used their MDIs an average of 2.5–3 times per day as in- structed, although almost 95% reported correct use as prescribed. Jo ́nasson et al found a decline in adherence with twice-daily inhaled budesonide and placebo in mildly asthmatic children over a 27-month period of monitoring remaining doses with Turbuhaler DPIs.25 A disturbing finding from Mawhinney et al was that only 1 subject out of 34 in a clinical trial of 2 nonbronchodi- lator anti-asthma drugs (cromolyn-like and corticoste- roid agents) was compliant with prescribed use, as mea- sured with a nebulizer chronolog for MDI.27 Such findings raise questions about the validity of clinical trials, when patient medication use is thought to be best.
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DETERMINANTS OF PATIENT ADHERENCE TO AN AEROSOL REGIMEN
Fig. 2. Percentage of prescribed doses of inhaled 2 agonists and inhaled corticosteroids over 13 weeks among asthmatic children. The chronolog record is the raw percentage of prescribed doses taken. “Doses taken at correct times” represents the percentage of prescribed doses with the correct number of puffs taken within the correct time window. The error bars indicate the minimum and maximum percentages. The boxes indicate the lower and upper quartiles (25% and 75% of subjects). The thick black horizontal bars indicate the medians of values reported or measured. (Adapted from Reference 4, with permission.)
Correct Aerosol Device Technique
Lack of adherence to aerosol therapy can be due to lack of understanding correct aerosol device or drug use, and was termed “unintentional” nonadherence in Table 1. Far- ber et al found that 23% of parents (n 131) misunder- stood the role of their asthmatic child’s inhaled anti-in- flammatory medication, believing that it was for treatment of symptoms after they occurred, not for prevention. This was associated with decreased adherence to its daily use.12
A number of studies have documented problems pa- tients have using aerosol devices and common patient er- rors, particularly with MDIs.30 –34 While “press and breathe” seems simple when using an MDI, many patients lack the coordination for the split-second timing required between actuating the MDI and beginning a slow inhalation.31 Sub- optimal therapeutic response and poor control of airway disease can result from faulty technique.31,35
Problems with patient use of aerosol devices can be worsened by inadequate knowledge of correct device use among health-care professionals. A study by Hanania et al of medical personnel’s knowledge of MDIs, MDIs with spacers, and a DPI had a mean SD knowledge score of 67 5% for respiratory therapists, 48 7% for house staff physicians, and 39 7% for registered nurses.36 A similar study of the same types of aerosol devices found that pharmacists lacked adequate knowledge to properly instruct patients in inhaler use.37 DPIs can remove the need for hand-breath coordination with MDIs (a common problem) because DPIs are breath-actuated. However, a recent study by Melani et al found similar percentages of
Table 3. Relation of Dosing Frequency to Compliance With a Prophylactic Inhaled Medication in Children Monitored With a Nebulizer Chronolog Monitor
Prescribed Frequency Reported Compliance Monitored Compliance (doses/day) (% of days) (% of days)
2 96 71 3 90 34 4 69 18
(Adapted from Reference 16.)
poor patient use with MDIs, compared to DPIs.38 In their study, 24% of patients used MDIs poorly; failure to cor- rectly perform essential steps with the Aerolizer, Turbu- haler, and Diskus was 17%, 23%, and 24%, respectively. Use of a large-volume spacer reduced poor MDI use from 24% to only 3% of patients.
Complexity of Inhalation Regimen
The complexity of an inhalation regimen in managing airway disease can depend on the frequency with which an inhaled medication must be taken, the number of medica- tions to be taken, and whether different types of aerosol devices must be used (eg, a nebulizer for one drug and a DPI for another).
Dosing Frequency
Medication adherence has been linked to the frequency with which a drug must be taken, for both oral and in- haled-drug regimens. Eisen et al used electronically mon- itored pill containers to measure patient adherence with antihypertensive medication.39 Their study found that ad- herence improved from 59% with a 3-times daily regimen to 83.6% with a once-daily regimen. Similarly, Cramer et al found the mean (SD) adherence rate for oral antiepilep- tic drugs was 87% (11), 81% (17), 77% (12), and 39% (24) for daily, twice-a-day, 3-times-a-day, and every-6-hours dosing, respectively, using an electronic pill bottle dis- pensing system.40 Prescribed frequency of drug use simi- larly affects inhaled medications. Coutts et al performed a pilot trial of the nebulizer chronolog to study compliance with inhaled prophylactic medication (corticosteroids) in children.16 Table 3 gives the results of their study for twice-a-day, 3-times-a-day, and every-6-hours dosing fre- quencies, with patient self-report and nebulizer chronolog monitoring data. A “compliant day” was defined as one with the correct number of puffs at appropriate times. As reported for oral medications, compliance declined with increasing frequency of use. Mann et al assigned patients to 2 groups, with group A taking 4 inhalations of fluni-
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solide twice a day, and group B taking 2 inhalations every 6 hours.41 Correct use was 8 inhalations per day, for either group. Both groups had a run-in period with 4 inhalations twice-a-day. Compliance did not change for group A (twice- a-day dosing) from the run-in period. The percentage of days with less than 8 inhalations for group B increased from 20.2 40.3% during the run-in, to 57.1 49.6% with the change to every-6-hours dosing. The mean num- ber of daily inhalations in group B decreased from 7.9 2.5% to 6.8 3.1% (p 0.01) between the 2 time peri- ods.
Combination Formulations of Inhaled Drugs
Combining 2 inhaled drugs into one formulation for inhalation could theoretically halve the number of times needed for drug administration, and thereby reduce the complexity for drug inhalation. Bosley et al reported a study in 1994 that compared separate inhalation of a cor- ticosteroid (budesonide) and a short-acting 2 agonist (ter- butaline) to a combination formulation of the two.42 All drugs were given using the Turbuhaler DPI and were to be taken twice daily. Adherence was monitored electronically with the Turbuhaler Inhalation Computer. When the 2 drugs were inhaled separately, compliance was similar for both the 2 agonist and the corticosteroid, at about 60–70%. This was somewhat surprising, since compliance with in- haled corticosteroid therapy is often thought to be poor, and worse than with bronchodilators.43 In addition, com- pliance was no better in patients using the combined for- mulation. These results may have been due to use of a short-acting 2 agonist, which requires more frequent use per day than a long-acting agent.
A study by Stoloff et al compared medication-refill per- sistence with (1) the corticosteroid fluticasone propionate and the long-acting 2 agonist salmeterol in combination in a single inhaler; (2) fluticasone propionate and salme- terol inhaled separately from 2 inhalers; (3) fluticasone propionate and montelukast taken together (inhaled, oral); and (4) fluticasone propionate and montelukast each taken singly as monotherapy.44 The cohort that used fluticasone plus salmeterol from a single inhaler had significantly bet- ter adherence (4.06 refills per 12-month period) than the other cohorts that used fluticasone (2.35 refills per 12- month period in the group that inhaled fluticasone and salmeterol from separate inhalers; 1.83 refills per 12-month period in the group that used fluticasone plus montelukast; and 2.27 refills per 12-month period in the group that used fluticasone alone). The combination formulation (flutica- sone plus salmeterol in one inhaler) had refill persistence similar to that of the oral leukotriene modifier montelukast taken alone (4.51 refills per 12-month period), although montelukast monotherapy had the highest refill persistence.
Fig. 3. Percentage of patient compliance with oral theophylline versus inhaled corticosteroids and cromolyn sodium, based on pharmacy claims data with a group of asthmatic subjects. The error bars represent the standard deviations. (Based on data from Reference 45.)
The difference in results between the study by Bosley et al,42 with a short-acting bronchodilator, and that of Stoloff et al,44 with a long-acting bronchodilator, may well be due to the frequency of administration. In addition, the sim- plest form of drug therapy in the Stoloff et al study was oral montelukast taken as monotherapy, which had the highest adherence.44 The recommended dosage for mon- telukast is once daily, taken as a pill.
Route of Administration: Oral Versus Aerosol
Taking a dose of medication as a pill is reasonably simple and quick, assuming normal swallowing ability and consciousness. In terms of time needed for a dose, the MDI and DPI are closest among the various aerosol de- vices to pill-taking, although the multiple steps needed for correct use of either (MDI: shaking, exhaling, actuating, slow inhalation, and breath-hold; DPI: multi-step prepara- tion, breath-hold) certainly requires a minute or more. In terms of simplicity, I would argue that a pill taken orally is far simpler than MDI or DPI use.
Kelloway et al used medical records together with phar- macy claims data to measure the compliance of patients prescribed oral theophylline and inhaled medications.45 All subjects used oral theophylline; 97% used inhaled corti- costeroids and 8.4% used inhaled cromolyn sodium, with 5% taking both inhaled cromolyn and inhaled steroids. Both theophylline and inhaled corticosteroid dosing regi- mens ranged between 2 and 3 times daily. Cromolyn is usually prescribed on a 4-times-daily basis. As shown in Figure 3, the highest compliance was with oral theophyl- line (79 34%), with inhaled corticosteroid and cromolyn at 54 43% and 44 34%, respectively. Since only a few patients had 2 inhaled formulations, the data from Kelloway et al suggest better adherence with oral drugs than with inhaled drugs. Compliance for oral theophylline was similar when patients were stratified into age groups of 12–17 years versus 18 – 65 years. Inhaled corticosteroid compliance was 30% in the younger group and 57% in the
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Table 4. Results on Adherence With Oral Versus Inhaled Medications From a Number of Studies
First Author, Year
Kelloway 199445
Sherman 200146 Maspero 200147 Bukstein 200348 Jones 200349
CI confidence interval
Measurement
Medical records Pharmacy data Prescription refills Patient interview Patient self-report Pharmacy claims
Oral Drug Theophylline 79 34
Montelukast 59 (95% CI 48–65) Montelukast 82
Montelukast 78
Leukotriene modifier 67.7
Inhaled Drug
Corticosteroid 54 43 Cromolyn 44 34
Fluticasone 44 (95% CI 35–50) Beclomethasone 45
Cromolyn 42
Inhaled corticosteroid 33.8 Long-acting 2 agonist 40.0
Condition Age Range (y)
Asthma 12–65
Asthma Pediatric Asthma 6–11 Asthma 6–11 Asthma 6–55
Adherence (%)
older group, indicating an age difference in that particular study.
Table 4 summarizes results from the study by Kelloway et al,45 together with other studies46 – 49 that compared pa- tient adherence with oral versus inhaled drug therapy.
Unfortunately, the studies listed in Table 4 all include inhaled therapy that must be taken multiple times daily. With the exception of the study by Kelloway et al, in which theophylline was prescribed, all of the other studies examined use of leukotriene modifiers, and most of these were the once-daily montelukast taken orally. Thus, there is some confounding of results between route of adminis- tration (oral vs inhaled) and frequency of dosing, with higher frequency of dosing for the inhaled drugs.
Type of Inhaled Medication: Inhaled Corticosteroids Versus 2 Agonists
There is a perception among clinicians that patient ad- herence with prescribed inhaled corticosteroids is worse than with inhaled 2 agonists. This has been attributed to the absence of immediate relief or perceptible effect from inhaled corticosteroids, compared to short-acting 2 ago- nists.43 A 2000 literature review by Cochrane et al of compliance with inhaled corticosteroids noted that studies have shown that patients took the recommended dose on 20–73% of days.50 Bosley et al compared a combination corticosteroid and 2 agonist inhaled formulation with sep- arate delivery and found no difference in compliance when the 2 drugs were taken separately.42 At least 2 other stud- ies have measured differences in adherence with inhaled corticosteroids and 2 agonists. Milgrom et al measured adherence of children with asthma to regimens of both inhaled corticosteroids and 2 agonists, using the MDI chronolog (also termed the nebulizer chronolog monitor).4 They found that doses taken within the correct time win- dow, as prescribed (the “time-corrected compliance”), were 48% for 2 agonists and 32% for inhaled corticosteroids. Median days without medication were 20.4% for 2 ago-
Fig. 4. Median percentage of days with no, minimal, or complete inhaled-medication use for corticosteroids and 2 agonists among 24 asthmatic children. (Based on data from Reference 51.)
nists and 24.4% for inhaled steroids. They noted that 25% of patients did not take inhaled corticosteroids on more than 60% of the days studied.
Bender et al also found better adherence with 2 ago- nists than with inhaled corticosteroids.51 The results of their study are shown in Figure 4. The studies by Milgrom et al4 and Bender et al51 both support the view that inhaled corticosteroid adherence appears to be worse than adher- ence with inhaled 2 agonists. It should be noted that in both studies the 2 agonists were probably short-acting, as opposed to long-acting, although the specific drugs were not identified. Since inhaled corticosteroids and short-act- ing 2 agonists were both prescribed multiple times daily, it would not seem that the poorer results with inhaled corticosteroids were due to frequency of dosing. It is not clear if similar results would be found if adherence with inhaled corticosteroids were compared to long-acting 2 agonists.
Patient Awareness of Monitoring and Effect of Feedback On Monitoring
Studies of patient adherence with inhaled medications have found that informing patients that they are being
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Fig. 5. Comparison of feedback and control groups on measures of adherence with metered-dose inhalers prescribed 3 times daily, among patients with chronic obstructive pulmonary disease. 2 sets/day percentage who averaged 2 sets per day. Days Adherent mean SD percent adherent days. Taken as Pre- scribed mean SD percent of total actuations taken as pre- scribed. (Based on data from Reference 52.)
monitored for correct drug use improves adherence. Tash- kin et al found that COPD patients who were uninformed of the nebulizer chronolog’s function had a 54% compli- ance rate, whereas a feedback group who was told of the nebulizer chronolog’s function had a 78% compliance with 3-times-daily MDI therapy.10 Nides et al divided COPD patients into a control group (n 89) and a feedback group (n 116).52 Actual adherence with prescribed MDI use 3-times-daily was monitored with the nebulizer chro- nolog. Patients in the control group were told only that the nebulizer chronolog recorded the amount of inhaled drug used, whereas the feedback group was told of the device’s ability to record the time and date of each MDI actuation. Adherence was recorded after a 4-month period. The mean SD number of MDI sets per day recorded by the nebulizer chronolog was 1.95 0.68 for the feedback group and 1.63 0.82 for the control group (p 0.003). Figure 5 illustrates the percentage of patients who aver- aged 2 or more MDI sets per day, the mean percent of adherent days, and the mean percent of total MDI actua- tions taken as prescribed. Fifteen percent of the control group had “canister dumping” episodes, actuating their inhalers at least 100 times within a 3-hour period shortly before the 4-month follow-up visit. No canister dumping episodes occurred with subjects in the feedback group. Simmons et al also found that a feedback group exhibited better adherence than did a control group of COPD pa- tients, over a 24-month follow-up period.28 At 4 months the control group had 1.60 0.83 sets of actuations per day, compared with 1.93 0.69 in the feedback group (perfect compliance was 3.0 sets per day). For both groups, compliance fell over the 24 months of follow-up, with actuations per day of 1.16 0.95 for the controls and 1.65 0.89 for the feedback group at 24 months. Another study by Simmons et al found that 30 of 101 COPD sub-
jects who were not informed of the function of the nebu- lizer chronolog actuated their inhalers 100 times within a 3-hour interval on at least one occasion.29 Only 1 of 135 subjects who had full knowledge of the nebulizer chro- nolog’s recording ability did so. Dumping episodes usu- ally occurred shortly before a clinic follow-up visit.
Patient Beliefs, Sociocultural, and Psychological Factors
In addition to the explicit factors such as understanding device use and instructions, complexity of inhalation reg- imen, and giving patients feedback on adherence, adher- ence can be influenced by a number of personal factors. These include health beliefs, such as need for medication, severity of disease, and risks of adverse effects, and so- ciocultural and psychological factors. Table 5 summarizes results from studies that examined the association of such factors with adherence to inhaled medications. There are some discrepancies among the studies. For example, Bos- ley et al found no association of socioeconomic status with adherence,13 whereas 2 studies by Apter et al found the reverse.53,54 Similarly, Horne and Weinman found that ed- ucational experience had no association with adherence,56 but the studies by Apter et al found this was associated with adherence.53–54 It may be that sample size and other sample factors explain the different findings. Variability in the relationship of age to adherence may be explained by different age groups in different studies. Horne and Wein- man found that, among adults, older age had a positive association with adherence.56 McQuaid et al found that older age had a negative association in a sample of children age 8–17 years.57 Jo ́nasson et al divided a sample of children age 7–16 years into 7–9 years and 10–16 years, and found that the older group had lower adherence than the younger group.25 A study by Labrecque et al reviewed pharmacy claims to investigate the effect of age on appropriate use of short-acting 2 agonists among asthma patients.58 They also found higher appropriate use among the younger patients (age 5–15 years) than among 15– 45-year-old patients.
The effect of patient education and self-management programs on corticosteroid use has been examined. Galle- foss and Bakke implemented an education program for asthma and COPD patients that consisted of a patient bro- chure, two 2-hour group-education sessions, individual ses- sions with a nurse or physiotherapist, and a treatment plan, with a control and treatment group.59 They found that steroid inhaler compliance measured from pharmacy records improved among asthmatics, from 32% among the controls to 57% among the program participants, which is almost a doubling. Among the COPD subjects, steroid inhaler compliance was 58% among the controls and 50% among the program participants, and education seemed to have little effect. However, in the educated group, amon
