Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD

Respiratory Medicine (2013) 107, 1481e1490

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/rmed

REVIEW

Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD ¨kela ¨ a,*, Vibeke Backer b, Morten Hedegaard c, Mika J. Ma Kjell Larsson d a Division of Allergy, Helsinki University Central Hospital, Skin and Allergy Hospital, PO Box 160, Helskinki, Hus 00029, Finland b Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark c AstraZeneca Nordic, Department of Health Economics, Copenhagen, Denmark d The National Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden

Received 3 December 2012; accepted 7 April 2013 Available online 3 May 2013

KEYWORDS Clinical outcomes; Healthcare resources; Quality of life; Therapy regimens; Respiratory disease

Summary Suboptimal adherence to pharmacological treatment of asthma and chronic obstructive pulmonary disease (COPD) has adverse effects on disease control and treatment costs. The reasons behind non-adherence revolve around patient knowledge/education, inhaler device convenience and satisfaction, age, adverse effects and medication costs. Age is of particular concern given the increasing prevalence of asthma in the young and increased rates of nonadherence in adolescents compared with children and adults. The correlation between adherence to inhaled pharmacological therapies for asthma and COPD and clinical efficacy is positive, with improved symptom control and lung function shown in most studies of adults, adolescents and children. Satisfaction with inhaler devices is also positively correlated with improved adherence and clinical outcomes, and reduced costs. Reductions in healthcare utilisation are consistently observed with good adherence; however, costs associated with general healthcare and lost productivity tend to be offset only in more adherent patients with severe disease, versus those with milder forms of asthma or COPD. Non-adherence is associated with

* Corresponding author. Tel.: þ358 94711; fax: þ358 94716500. E-mail address: [email protected] (M.J. Ma ¨kela ¨). 0954-6111/$ - see front matter ª 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.rmed.2013.04.005

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M.J. Ma ¨kela ¨ et al. higher healthcare utilisation and costs, and reductions in health-related quality of life, and remains problematic on an individual, societal and economic level. Further development of measures to improve adherence is needed to fully address these issues. ª 2013 Published by Elsevier Ltd.

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1482 Adherence issues in asthma and COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1483 Factors affecting adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1483 Inhaler devices and adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1484 Effect of adherence on clinical efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1484 Effect of adherence on costs and health outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1485 Summary and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1485 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487 Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1487

Introduction Asthma and chronic obstructive pulmonary disease (COPD) are two of the leading causes of morbidity, mortality and economic burden worldwide.1 Approximately 235 million people are thought to suffer from asthma globally,2 and 65 million are affected by moderate-to-severe COPD.1 The World Health Organization (WHO) estimates that chronic respiratory diseases represent 5% of total disease burden and 8.3% of chronic disease burden worldwide, accounting for more than 4 million deaths each year.1 COPD is expected to be the third leading cause of mortality by 2030.1 The burden of chronic respiratory diseases has major adverse effects on the quality of life and ability of affected individuals. Indeed, asthma and COPD are ranked 22nd and 10th, respectively, in terms of the leading causes of disease burden when assessed using disability-adjusted life years.2 Comorbidities are significant contributors to the individual, societal and economic burden of asthma and COPD.3e5 Further compounding the burden of these conditions are their increasing prevalence, especially in children, adolescents, the elderly and those from poorer countries.1 Unsurprisingly, the economic cost associated with COPD and asthma is considerable. For COPD, the associated costs are of crucial importance given the ageing population and the expected corresponding increase in the prevalence of the condition. Cost estimates for asthma vary, and have been shown to increase with disease severity.6 A Finnish analysis suggests that 1e2% of total healthcare expenditure across industrialised nations is attributable to asthma.7 Although data from low- and middle-income countries are lacking, in the USA alone annual COPD-associated costs were more than $US32 billion in 2005.8 Given the increasing prevalence of asthma and COPD, and the relationship between cost and disease severity, effective treatment and management of these diseases is crucial in improving clinical and economic outcomes.

A variety of effective treatment options exist for patients with asthma and COPD, but long-term adherence to medication is required for treatment success.9,10 Poor patient adherence to therapy can have detrimental effects on outcomes, resulting in higher healthcare costs.11 Regardless of illness type, poor adherence (often defined as 80% adherence) is one of the main factors responsible for failure to achieve treatment goals, and may also carry a large economic burden as a result of increased healthcare costs and unused medications. Given the intrinsic connection between adherence, clinical outcomes and economic cost, this review examines adherence issues in asthma and COPD, factors that affect adherence, including evidence for correlations between the correct use of inhaler devices and improved adherence, effects of adherence on clinical efficacy and costs/health outcomes in patients receiving inhaled therapies for asthma or COPD. A search of MEDLINE and EMBASE was conducted using the following criteria: asthma [drug therapy] OR chronic obstructive pulmonary disease [drug therapy] AND (patient compliance OR medication adherence OR patient adherence OR non-adherence OR patient preference OR patient satisfaction). Results were limited to English language publications of clinical studies published between January 2000 and April 2012; no other specific inclusion/exclusion criteria were applied. An additional manual search of PubMed was conducted for comprehensiveness using the following key words: asthma, chronic obstructive pulmonary disease and adherence. The same limitations were applied as noted above. The resulting reference lists were hand searched, and a further three relevant papers were identified for inclusion. In total, 99 relevant papers were identified for analysis. It should be noted that there was a distinct lack of published material related to nonadherence due to comorbidities in the elderly; therefore, this topic was not covered in-depth. Furthermore, the aim of this literature review was to examine the evidence for

Adherence of inhaled therapies for asthma and COPD

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correlations between the correct use of inhaler devices and improved adherence. For this reason, detailed discussion of adherence issues in specific subgroups of patients was beyond the scope of this review.

Adherence issues in asthma and COPD Adherence to treatment can be broadly defined as ‘the extent to which a person’s behaviour corresponds with the agreed recommendations from a healthcare provider’.12 Although the terms ‘compliance’ and ‘adherence’ are often used interchangeably, not least in databases, there are subtle differences between the two (‘compliance’ infers a lack of patient involvement), and ‘adherence’ is generally the preferred term.13 According to WHO estimates, only 50% of patients receiving long-term pharmacotherapy for chronic diseases are adherent to treatment (no precise definition of good versus poor adherence was provided)12; adherence rates in asthma and COPD have been shown to vary widely from 22% to 78%.14e17 Although treatment success in asthma and COPD is largely dependent upon medication adherence, suboptimal disease management, including the failure of physicians to adhere to treatment guidelines, also plays a part.18 Patients with asthma and COPD receive a lot of information, including education on the disease processes, likely comorbidities, risk factors, and the medications and devices involved in treatment. In addition to starting pharmacological treatment, patients may also be instructed to cease smoking or make other lifestyle changes.18 These factors may impact on adherence. The majority of studies in asthma and COPD focus on pharmacological adherence, as this is arguably the easiest factor to measure; however, there is considerable variability in the definitions and measurements of patient adherence across studies. Methods of measurement include prescription refill adherence (based on pharmacy records, manual/electronic recording of collected prescriptions or national/provincial database records), medication possession ratios (calculated by dividing the number of days supplied for a medication by the number of days in the study)19 and self-report measures (including medication adherence rating scales such as the Morisky Medication Adherence Scale20). More precise measures include electronic monitoring of dose actuations or manual dose/pill-counting. The majority of studies in asthma and COPD use prescription refill adherence or selfreport measures to measure pharmacological adherence, although electronic dose monitoring is rising in popularity, most likely because of its precision. Of the studies investigating adherence in asthma and COPD since 2000, the most frequently used methods to assess adherence were self-report measures (37.8%), prescription refill data (32.8%) and electronic monitoring (19.3%) (Fig. 1). Many studies employ both subjective and objective measures, for instance a self-report scale in addition to prescription refill adherence.21e36

Factors affecting adherence The reasons for suboptimal adherence to inhaled asthma and COPD therapies are multifaceted (Table 1). However,

Fig. 1 Most commonly used measures of adherence in studies investigating inhaled asthma/chronic obstructive pulmonary disease therapies from 2000 to 2012. Total percentage may not add up to 100% as studies may have used more than one adherence measure.

the negative association between suboptimal adherence and poor disease control is clear.21,37e40 Factors thought to influence adherence to inhaled medications include patient age, level of education/knowledge about the conditions, medication and delivery devices, time to onset of symptom relief, symptom severity, regimen complexity (ease of use, dosing frequency, number of medications), cost, comorbidities (additional medications, effect of other conditions on adherence [e.g., depression]), adverse effects of medication and poor doctor-patient communication.41e43 Adherence to inhaled therapies is worse than that seen with oral44e47 or injected48 therapies in patients with asthma, including children,26,49 and transdermal therapies in patients with COPD.50 This is unsurprising given the usual patient preference for easily administered medicines such as once-daily oral tablets or once-weekly injections, as well as the fact that patients may not believe that inhaled medication is valuable. However, one recent study demonstrated similar rates of adherence with the oral

Table 1 Factors associated with poor adherence (adapted from GINA Report, 2011 update).9 Drug factors

Non-drug factors

Difficulties with inhaler devices Complex regimens

Misunderstanding or lack of instruction Dissatisfaction with healthcare professionals Unexpressed/undiscussed fears or concerns Inappropriate expectations Poor supervision, training or follow-up Anger about condition or treatment Underestimation of disease severity Cultural or religious issues Stigmatisation Forgetfulness/complacency Attitude towards ill health

Side effects Medication costs Dislike of medication(s) Distant pharmacies Fears about side effects

GINA, Global Initiative for Asthma.

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leukotriene receptor antagonist montelukast and inhaled corticosteroids (ICS) in paediatric patients with asthma,51 suggesting this is not always the case when the parents are responsible for the anti-asthma treatment, which might be different from situations in which adolescents and young adults are taking care of the asthma management themselves. Age may play a role in adherence to treatment in asthma and COPD, with some studies showing older adults to be more adherent to treatment than younger adults,16,36,40 while others have shown no difference.31 Adherence to inhaled asthma therapy tends to be worse in adolescents than in younger children and in adults.28,52e54 The reasons for belowoptimal adherence are often similar to those in adults, e.g., lack of knowledge and incorrect assumptions about treatment/medication and illness, the consequences of which depend on the severity of the disease. However, incorrect assumptions about the illness may be more widespread if more young patients are symptom-free. Denial (either of the condition or of its severity), embarrassment and rebellion may be more relevant to non-adherence in this population.55,56 Peer expectations may also negatively influence an adolescent’s adherence behaviour. Simply put, nonadherence can be intentional (will not adhere) or nonintentional (cannot adhere). Although it may be tempting to assume that adolescents are more prone to the former than the latter, true intentional non-adherence is a complicated issue and very few patients neglect their condition for the purpose of harming themselves deliberately.56 A recent study has suggested that educating parents about their child’s allergic status and probable relationship to the child’s asthma may improve adherence to inhaled therapy.57 Parents of asthmatic children who underwent skin prick testing were more likely to adhere to scheduled continuity visits. This is the first evidence of such a finding, and may have important implications for adherence in children, and even adults. One may also speculate that objective diagnostic tests confirming the presence of asthma may modify the patient’s beliefs sufficiently for them to see the importance of good adherence (often defined as >80% adherence) to therapy. However, this is the only study demonstrating such data, and this area requires further research.

establish the connection between the type of inhaler device and treatment adherence. Frequency of dose administration is often described as a contributing factor to poor adherence, and a high daily frequency of inhaled drug administration (four times daily versus twice daily) has been shown to negatively influence adherence to medication in an asthma trial.63 A significant correlation has also been demonstrated between patient satisfaction with their inhaler and adherence (defined as the extent to which patients were perceived to follow their physician’s prescribing instructions/advice) in asthma,30 suggesting that the more satisfied the patient is with their device, the more likely they are to be adherent to treatment, and, therefore, are more likely to experience improved clinical outcomes and quality of life. However, correlations in this study were weak, potentially because physicians often interpret patient adherence poorly. Furthermore, as improved inhalation technique has been shown to improve adherence to asthma therapy (possibly due to the positive reinforcing effects of improved symptom relief concurrent with improved medication administration), it is crucial that repeated instruction on this point is provided to patients from the outset.33,54 A recent report from the European Respiratory Society and the International Society for Aerosols in Medicine recommends that patients remain on their current inhaler if their disease is stable, rather than switching to another device.64 A switch in devices can result in incorrect device technique (because of lack of education and experience with the new device), leading to suboptimal drug administration, poor treatment adherence and, therefore, decreased asthma control. In support of this, a recent study demonstrated that asthma control worsened when the inhaler was switched without patient consent.65 Given the association between inhaler satisfaction and adherence, it is essential that the patient is fully involved in the choice of device, and that their preferences are taken into account when considering a switch of inhaler. In line with this, it has recently been demonstrated that there is a paucity of guidance for the use of devices in asthma and COPD treatment guidelines.66 Increased guidance on the use of devices may improve physician awareness of relevant issues, potentially improving treatment outcomes.

Inhaler devices and adherence

Effect of adherence on clinical efficacy

Multiple-inhaler use has been associated with higher rates of non-adherence than single-inhaler use in both asthma and COPD patients e potentially because of the increased complexity introduced by the additional inhaler(s).32,58e60 Although one study found that certain inhaler types may be associated with higher rates of adherence than others in patients with asthma receiving ICS,61 data in this area are lacking and it is important to note that individual patients will have different device preferences. Better adherence has also been observed when patients are treated with combination ICS/long-acting b2-agonists (LABA) therapy compared with ICS alone (72.2% versus 40.5%, respectively, p Z 0.001), possibly due to the positive reinforcing effects of improved and more immediate symptom control with combination therapy.62 More studies are necessary to fully

The association between adherence to inhaled asthma and COPD therapy and clinical effect varies in the literature. Generally, good adherence is associated with better symptom control in patients with asthma, including children and adolescents.22,29,31,58,67e71 However, some studies, including those in children and adolescents,72,73 have shown no correlation between adherence and asthma control,74e76 while inconsistent associations have also been noted between the two.47 Numerous factors may be responsible for this variation, including population bias and differences in adherence assessment and reporting methods; however, there is general consensus that improved adherence to asthma therapy improves clinical outcomes. Overall, studies indicate that improved adherence leads to improvements in lung function in patients

Adherence of inhaled therapies for asthma and COPD with asthma,22,77 although some studies did not find any such correlation.36,78 Good adherence is associated with reduced exacerbation rates in patients with asthma19,79,80 and COPD.81 A subanalysis of the TORCH (Towards a Revolution in COPD Health) study showed that good adherence to study medication in patients with COPD (n Z 6112) was associated with lower mortality rates compared with poor adherence (11.3% versus 26.4%).82 This effect was maintained over a 3year period, regardless of treatment (Table 2). In line with this, a population-based cohort analysis demonstrated that the asthma-related death rate decreased by 21% with each additional canister of ICS used by a patient in the previous year (Table 3).83 Whilst it is relatively easy to identify a correlation between adherence and outcomes with ‘hard’ endpoints such as mortality, correlations are more difficult to see with less clear-cut endpoints such as the more subtle changes in disease control. Furthermore, the association between adherence and mortality may be indirect, contingent on fundamental patient characteristics that underlie adherence (e.g., risk behaviour). However, the available data indicate that improved adherence results in improved medication delivery and, therefore, improved clinical efficacy and better disease control.

Effect of adherence on costs and health outcomes Good adherence is correlated with reductions in healthcare utilisation in patients with asthma30,38,75,84 and COPD,81 as well as in children and adolescents with asthma.39,69,72 In contrast, COPD exacerbations are associated with an increase in healthcare utilisation, providing an explanation for the fact that exacerbations are a main cost driver in both asthma and COPD; one British study showed that patients who experienced an asthma attack incurred healthcare costs 3.5 times greater (costs per patient over a 1-year period) than those who did not.85 Similarly, in patients with COPD, exacerbations are thought to be responsible for 35e45% of all healthcare costs associated with the disease.86 In support of this, a retrospective study using a large administrative claims database showed that higher adherence rates are correlated with reduced urgent care usage (annual number of inpatient days, inpatient visits and emergency room visits) in patients

Table 2 3-Year mortality rates in patients with COPD with good or poor adherence.82 Therapy

Salmeterol Fluticasone propionate Combination salmeterol/ fluticasone propionate Placebo

3-Year mortality rates (%) Good adherence

Poor adherence

10.7 12.9 9.5

25.2 28.7 24.9

12.0

26.7

Good adherence was defined as an average adherence to study medications of >80% over the whole period the subject was in the study; poor adherence was defined as 80%.

1485 with COPD (n Z 55,076).81 However, studies have also demonstrated no difference between patients with asthma who are adherent and non-adherent to treatment in terms of healthcare utilisation (emergency room visits), in both adults31 and adolescents.78 As with any improvements in clinical outcomes, patients in the latter two studies may have had milder forms of asthma, and, consequently, any reductions in healthcare utilisation associated with diseaserelated events may have been insufficient to offset the possible increase in medication costs and/or physician visits associated with improved adherence. Costs associated with general healthcare39 and lost productivity87 tend to be higher in patients with asthma who are non-adherent to treatment versus those who are adherent. However, one large retrospective observational study demonstrated that savings generated by reductions in high-cost events did not offset the increased drug costs for more adherent patients with asthma, with the exception of high-risk patients with more severe asthma.88 These results support the suggestion that the cost benefit of improved adherence may be more marked in patients with more severe forms of respiratory disease. Additionally, it is possible that significant cost savings are not seen early in the disease process (as exacerbations are more mild and thus less costly to treat), but may be found as the disease progresses, with more severe exacerbations requiring more expensive treatments. Consequently, to account for this effect, economic analyses of treatments that potentially slow disease progression should be designed to capture an appropriate time period. Quality of life is also presumed to increase in tandem with adherence. Although the literature is somewhat inconsistent, with some studies reporting no change in quality-of-life scores despite improved adherence,74,87 overall, good adherence is associated with improvements in health-related quality of life (generally through reduced exacerbations and improved symptoms) in patients with asthma30,33,77 and COPD,89 including adolescents.90

Summary and discussion Despite the range of effective pharmacological treatments available for asthma and COPD, many patients still do not achieve treatment goals, in part because of poor adherence to therapy. Non-adherence to treatment is associated with poor symptom control, higher healthcare utilisation and healthcare costs, and reductions in health-related quality of life. These findings are consistent with those in other chronic disease areas such as cardiovascular disease and diabetes mellitus. In patients with hypertension, non-adherence and poor persistence with antihypertensive medications are associated with uncontrolled hypertension, poor clinical cardiovascular-related outcomes and increases in healthcare costs.91 A recent review estimated that only 50% of hypertensive patients are adherent to their treatment regimens after 1 year.92 Adherence rates of 36e93% and 73e86% have been shown in type 2 diabetes mellitus patients receiving oral antihyperglycaemic therapy or insulin, respectively.11 Given the correlation between adherence and clinical outcome for cardiovascular disease and

1486 Table 3 usea.83

M.J. Ma ¨kela ¨ et al. Crude and adjusted rate ratios for death from asthma in relation to discontinuation from inhaled corticosteroid

Corticosteroid use Uninterrupted (%) Discontinued (%) 1e3 months before index date 4e6 months before index date 7e9 months before index date

Case patients (N Z 66)

Controls (N Z 2681)

Crude rate ratio

Adjusted rate ratio (95% CI)b

4.6

7.9

1.0

1.0c

19.7 4.6 4.6

9.0 6.3 5.3

3.9 1.3 1.7

4.6 (1.1, 19.1) 1.8 (0.3, 10.9) 1.6 (0.3, 9.4)

CI, confidence interval a Index date for cases and matched controls was the date of the case patient’s death from asthma. b Rate ratios are adjusted for age and sex; the number of prescriptions for theophylline, nebulised and oral b-adrenergic agonists and oral corticosteroids the year before the index date; the number of canisters of inhaled b-adrenergic agonists dispensed in the year before the index date; and the number of hospitalisations for asthma during the two years before the index date. c Denotes reference group.

diabetes mellitus, it is unsurprising that adherence to treatment and sustained disease control are associated with reduced annual healthcare costs93; however, unfortunately high rates of under-treatment and non-adherence persist. In line with findings in asthma,25 adolescents (aged 10e20 years) with diabetes mellitus were more likely to be poorly adherent and have worse glycaemic control than younger and older patients in a systematic review.94 This finding is important, as it suggests that adolescents may be at greater risk of non-adherence, and therefore, at greater risk of poor disease control and worse clinical outcomes. The confirmation of this finding in another chronic disease setting identifies this patient population as a target for increased intervention to improve adherence. Furthermore, poor adherence has been demonstrated to be a significant factor in asthma-related death and near-miss cases in adolescents,95 as well as the presence of more severe disease96 and poorer quality of life in this population.28 Targeting non-adherence is, therefore, particularly important for physicians responsible for younger patients, predominantly adolescents, for whom issues related to image/ expectations, cost and convenience impact substantially on adherence.28,78 It may also be appropriate for adolescents to be moved from the care of a paediatrician to an adult clinic in order to gain traction when attempting to modify adherence behaviours.97 Limited clinical trial evidence for adherence in older patients (aged 65 years) was available. However, one recent review of asthma in the elderly98 suggested that older patients with asthma may intentionally decide not to adhere to treatment, generally because of poor knowledge of the disease, treatment or the consequences of poor adherence. As with younger patients, older patients may also display non-intentional poor adherence due to comorbidities or a combination of cognitive and physical decline; for instance, impaired vision or musculoskeletal conditions may affect their ability to use an inhaler correctly.98 Furthermore, a letter to the Editor of the Lancet published in 2006 concluded that assistance by caregivers is an important strategy in combating poor adherence to ICS therapy in elderly asthma patients with complications (such as cognitive and motor dysfunction).99 Similarly, while there is a general understanding that patients prefer fewer daily medication doses, we did not identify any clinical trials that have assessed this in a

controlled environment. However, two administrative database assessments100,101 have shown that patients, including adolescents and young adults,101 receiving oncedaily therapy for asthma are more adherent to treatment than those prescribed twice-daily treatment. Given the numerous factors driving non-adherence to inhaled asthma and COPD therapy, there are many points at which healthcare professionals could intervene to improve adherence. Patient perception is an important target, as how the patient feels about their illness, medication, inhaler and even their healthcare professional can influence how likely they are to adhere to their treatment regimen.18 Patient education is also crucial; this can occur on multiple levels, including the disease itself, the medication and the device. Regimen convenience can also be targeted by physicians; a variety of combination inhalers now exist, reducing the number of inhalers patients must carry with them. For example, patients receiving maintenance therapy who require both ICS and LABA experience greater convenience with fixed ICS/LABA combination inhalers, which require only two administrations per day compared with the more frequent schedules indicated by older formulations. It is crucial that patients are able to operate their inhaler correctly, and this should be evaluated by a physician or nurse during a clinic visit. A clear explanation of how to use an inhaler is required,18 as patients may initially find using different inhalers difficult and their understanding of written instructional materials will vary.102 To reinforce correct use of the inhaler, it is important for the healthcare professional to repeat these instructions at subsequent visits.33 Despite the positive association between device satisfaction and clinical outcome, there is no information to suggest any link between adherence to specific devices and clinical health outcomes or costs. Given the range of devices currently available for asthma and COPD, such data are likely to be clinically useful, as well as important for future pharmacoeconomic analyses. Further research in this area would be of great clinical relevance. In general, good adherence to inhaled therapies is correlated with reductions in healthcare resource utilisation (including costs associated with direct healthcare and lost productivity) in both asthma and COPD, and in adults, children and adolescents. However, there is evidence to suggest that the costs associated with adherence to asthma

Adherence of inhaled therapies for asthma and COPD treatment are not offset in patients with milder disease. The reasons for this are unclear, but as increased adherence is thought to be associated with a reduced economic burden, this finding warrants further investigation to establish the implications for future adherence interventions. One possible explanation may be that any short-term economic savings achieved through frequent changes of inhaler device are actually offset over time, if they result in decreased adherence and, subsequently, worse outcomes.

Conclusions Suboptimal or non-adherence to inhaled therapies for asthma and COPD is associated with poor symptom control, higher healthcare utilisation and healthcare costs, and reductions in health-related quality of life. The findings reviewed here suggest that poor adherence to inhaled therapies is common among patients with asthma and COPD, and is particularly problematic in adolescents with asthma. Furthermore, patient satisfaction with their inhaler is positively correlated with improved adherence, clinical outcomes and treatment costs. Given the growing prevalence of these conditions in the young, this disparity in adherence between adolescents and adults may have significant consequences for healthcare costs, and society in general, if the issue remains unaddressed. Additional research is required to identify measures that can improve adherence in order to address these questions.

Acknowledgements This review was funded by AstraZeneca. Medical writing assistance for this review was provided by Claire Pouwels and Anna Mett of in Science Communications, Springer Healthcare. This assistance was funded by AstraZeneca.

Conflicts of interest MM has received lecture fees from GlaxoSmithKline and MSD, and has been reimbursed for attending a symposium by MSD; MM has also received consultation fees from AstraZeneca and Orion Pharma. VB has no conflicts to declare. MH is a full-time employee of AstraZeneca Nordic. KL has, during the last 5 years, on one or more occasion been a member of an advisory board and/or served as a speaker and/or participated in educational events arranged by AstraZeneca, BoehringerIngelheim, GlaxoSmithKline, Meda, MSD, Nycomed, Novartis and Pfizer; KL has also, during the last 5 years, received unrestricted research grants from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline.

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