Inhaler Devices for Patients with COPD

COPD, 10:1–13, 2013 ISSN: 1541-2555 print / 1541-2563 online Copyright © Informa Healthcare USA, Inc. DOI: 10.3109/15412555.2012.761960

REVIEW

Inhaler Devices for Patients with COPD

COPD Downloaded from informahealthcare.com by Robert Joy on 05/13/13 For personal use only.

James B. Fink,1 Gene L. Colice,2 and Rick Hodder3,* 1

Respiratory Therapy Program at Georgia State University, Atlanta, Georgia, USA

2

Department of Pulmonary, Critical Care, and Respiratory Services, Washington Hospital Center, Washington, DC, USA

3

Divisions of Pulmonary and Critical Care, University of Ottawa, Ottawa, Canada

Abstract Chronic obstructive pulmonary disease (COPD) continues to be associated with increased morbidity and mortality risk in spite of updated guidelines and a better understanding of this condition. Progressive airflow limitation and resultant hyperinflation—the respiratory hallmarks of this complex and often underdiagnosed disease—can be treated with pharmacotherapies emitted via nebulizers, pressurized metered-dose inhalers, dry powder inhalers, or a Soft Mist inhaler. Pharmaceutical company proprietary issues, technological innovations, and societal pressure have expanded the list of available inhalers, with a limited range of medications available for any one device. Each device has different operating and maintenance instructions, and successful use of a given drug/device combination requires that patients understand, maintain, and use each of their devices properly in order to ensure consistent and optimal pulmonary drug delivery. Clinicians are faced with a range of physical and psychosocial issues unique to each patient with COPD that must be overcome in order to match a suitable inhaler to the individual. Improved drug delivery afforded by next-generation inhalers, coupled with an awareness of device-specific and patient-specific variables affecting inhaler use, may improve clinical outcomes in the treatment of COPD.

Introduction

*Sadly, Rick Hodder passed away after completion of this article. This article was developed on the basis of the authors’ presentations and discussions at the “Implications of Inhalation Delivery Systems for COPD Therapies” Advisory Board held in New York, New York, USA, March 25–26, 2009. Keywords: Chronic obstructive pulmonary disease, aerosol, dry powder inhaler, metered-dose inhaler, Soft Mist inhaler, nebulizer Correspondence to: James B. Fink PhD, RRT, FAARC, 1526 Seneca Lane, San Mateo, CA 94402, USA, phone: +1 (650) 703-7083, fax: +1 (650) 2273279, email: [email protected]

Progressive airflow limitation, a hallmark of chronic obstructive pulmonary disease (COPD), is attributed to a heterogeneous mixture of lung structural h abnormalities (small airway disease and destruction of parenchyma), which hich vary among individuals (1). Fortunately, COPD is a treatable disease, which ic and nd d is amenable to stepwise and cumulative non-pharmacotherapeutic ative ve pharmacotherapeutic management, such as outlined in the Global Initiative ho od l odi for Obstructive Lung Disease (GOLD) guidelines (1). Inhaled bronchodilaShort-acthor ort actttor medications are central to the treatment of COPD (Tablee 1). Sh sttage ges off the th ing beta-agonists (SABAs) can be used as needed duringg all stages disease (1). t-acting tingg anticholinergic ant antichol an c olineeerrgi cho rg In addition, a combination of a SABA and a short-acting an either heer on onee al alo alone lon ne in i the hee (SAAC) has been shown to be more effective than nticholinergics oline ner ergics icss (L (LAAC ((LAACs) AA AC ) aand nd symptomatic relief of COPD (2). Long-acting anticholinergics intenance anc nce ce monotherapies m mon notheera erap apiess concon n-long-acting beta-agonists (LABAs) are maintenance ent than an S SABAs SA BA As or or SAACs SA AACs for f r the th h sidered to be more effective and convenient PD (1). 1).. A Add Addition tio ion of aan n inhaled nh ha ed d ccortirtii-stage-appropriate management of COPD nchodilator dilato ator iss an app appropriate pprop pp pria iat option optti n for op ffo costeroid (ICS) to a long-acting bronchodilator vere and an nd d ve veryy se ssevere ev ree C COPD OPD PD and nd recurrent ecu cu cur urr the treatment of patients with severe rom the he llit literature eratu attu e ha has a al also llsso underscored nd d rssco c re the co exacerbations (1). Evidence from enance ce inh in inhalation nhalatio ion pharmacotherapies harmac acoth thera erapiees in patients long-term benefits of maintenance 1

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Table 1. Examples of inhalers containing one or more COPD medications


SABAs • Albuterol (Proventil® HFA, Ventolin® HFA, ProAir® HFA) • Levalbuterol (Xopenex® HFA) SAACs • Ipratropium (Atrovent® HFA, nebulizer) SABA/SAAC combinations • Ipratropium/Albuterol (Combivent® CFC, DuoNeb® Inhalation Solution nebulizer, Respimat® SMI) • Ipratropium/Fenoterol (Berodual® Inhalation Solution nebulizer, HFA pMDI, Respimat® SMI) LABAs • Formoterol (Foradil® Aerolizer® DPI, Foradil® Certihaler® DPI, Perforomist® Inhalation Solution nebulizer) • Arfomoterol (Brovana® Inhalation Solution nebulizer) • Salmeterol (Serevent® Diskus® DPI) LAAC • Tiotropium (Spiriva® HandiHaler® DPI, Respimat® SMI) • LABA/ICS combinations • Salmeterol/fluticasone (Advair® Diskus® DPI, Advair® HFA) • Budesonide/Formoterol (Symbicort® Turbuhaler® DPI) SABA = short-acting β2-agonist, SAAC = short-acting anticholinergic, LABA = longacting β2-agonist, LAAC = long-acting anticholinergic, ICS = inhaled corticosteroid, CFC = chlorofluorocarbon, HFA = hydrofluoroalkane, pMDI = pressurized metered-dose inhalers, DPI = dry powder inhaler, SMI = Soft Mist inhaler.

with COPD, including reducing exacerbation rates, as well as improving lung function, exercise tolerance, and health-related quality of life (3–7). Inhalation of prescribed COPD drugs (Table 1) directly into the airways remains the preferred route because of rapid efficacy and the low incidence of systemic side effects relative to oral administration (8,9). The bronchodilator and/or anti-inflammatory effects of inhaled medications may be a consequence of their interactions with specific receptors located in the airways (10), airway smooth muscle (11), and other parts of the respiratory tract (12). The effectiveness of aerosolized respiratory drugs is also greatly dependent on the efficiency and pattern of pulmonary drug deposition, which is separate from the nominal inhaled dose (13–15). Targeted delivery of COPD medications to the lungs can be achieved with devices designed to emit respirable sprays of liquid droplets or solid particles. Particle size is documented to be an important factor in determining optimal pulmonary deposition of drug aerosols (16,17). Zanen et al. (17) examined the effect on lung function of monodisperse anticholinergic (ipratropium bromide) and β2-agonist (albuterol) aerosols. They demonstrated that the optimal particle mass median aerodynamic diameter (MMAD) for improving expiratory flow in study subjects with severe airflow obstruction (forced expiratory volume in one second [FEV1] 20%) drug deposition, and availability in the range of drugs required by patients (47). Devices that minimize the need to attain a mid- or high-PIF to achieve optimal drug deposition in the lungs may be preferred for patients for whom reaching an adequate PIF is problematic. Inhalers should incorporate safety features to warn users when the inhaler should be replaced. Visible and/ or audible prompts should provide ways to monitor inhaler use. Inhalers should be resistant to bacterial or fungal contamination. Ideally, these devices should only require a minimal number of device maintenance steps, especially if more than one inhaler is required to control symptoms. Drug–device combinations with environmentally friendly propellants or propellant-free inhalers that are easy to use by the patient, while at the same time ensuring efficient, safe targeting of COPD drugs to the respiratory tract, may be preferred. Table 3 lists preferred versus actual inhaler properties relevant to patients (16,21,23,48–54). All approved inhalers must meet regulatory requirements for consistent dose emission under label

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Table 3. Preferred versus actual inhaler properties relevant to patients (16,21,23,48–54) Preferred Properties of a User-friendly Inhaler

Nebulizer

pMDI

DPI

SMI

Lung deposition Low oropharyngeal deposition

~6–20%

~4–55%

~10–40%

46–57%

10–20%

~30–85%

~50–80%

15–24%

8–10 steps

6 steps

Range from 6–17 steps; simplicity varies widely among DPIs

5 steps

Regular washing and daily disinfection required

Periodic cleaning required; wash/dry actuator

Periodic cleaning required; varies by device

Periodic cleaning required; damp cloth to mouthpiece

No (5–20 min)

Yes

Yes

Yes

Small size and easy to carry

No

Yes

Generally

Heavier than pMDI or DPI

Multi-dose convenience

No

Yes

Some DPIs are single-dose units

Yes

Resistance to bacterial contamination

No

Yes

Yes

Yes

Impacted by environmental temperature and humidity

No

Yes (CFC more than HFA)

Yes

No

Dose counter

No

On newer HFA designs

Yes – vary in sophistication

Yes

>60% to atmosphere

Prime to atmosphere and exhaled

Only exhaled

Prime to atmosphere and exhaled

Specific device design available with range of COPD drugs required

Yes

No

No

No

Functional placebo devices available for teaching

Yes

Varies by manufacturer

Varies according to device

Yes

No propellants

CFCs and HFAs have global warming potential

No propellants

No propellants

Limited acceptance (Noise, size, and maintenance issues)

Generally well accepted



Simple to use

Easy to maintain


Short treatment time

Low ambient aerosol contamination

Environmental impact Liked by patients and physicians

pMDI = pressurized metered-dose inhaler, DPI = dry powder inhaler, SMI = Soft Mist inhaler, CFC = chlorofluorocarbon, HFA = hydrofluoroalkane.

conditions and, when used properly, results obtained under controlled conditions have shown that there is no difference in medication delivery (55); however, evidence from the literature also suggests that many patients in real-world settings are unable to use their prescribed inhalers properly (28,56–58), resulting in the possibility of variations in inhaled drug doses because of handling errors – an important consideration when tailoring inhalers according to patient needs.

Nebulizers Compressor-driven nebulizers predate the introduction of inhalers in the treatment of patients both in the hospital and in the home (Figure 1). Almost any hospitalized or outpatient can use a nebulizer driven by compressed gas (59). Some of the advantages of nebulizers include: the capacity to generate aerosols using a variety of water-soluble medications; the lack of requirement for a proper ‘press and breathe’ technique, and the absence of propellants. Although representing a great advance for clinic and home care at the beginning of the last century, GOLD only recommends nebulizer therapy for patients

with stable COPD unless “clear symptomatic benefit that cannot be achieved by simpler, cheaper, and more portable alternatives” (1). Hess et al. (60) reported that nebulizer characteristics such as fill volume, flow, and brand can affect device performance. Moreover, the small volume nebulizer with compressor dominates the home COPD nebulizer market. Nebulized drugs from a comparative study of 12 compressor/jet nebulizers showed considerable variation in output in terms of particle sizes, suggesting that several differences existed in the performance of the devices under investigation (61). Compressors are relatively heavy, bulky, and noisy compared with inhalers, requiring either electricity or battery power, and offer limited portability (55). Ultrasonic nebulizers are typically smaller and battery-operated, but are associated with maintenance problems and reliability issues for home use. In the past decade, vibrating mesh nebulizers have been introduced, which provide greater portability and reliability but at a substantially higher cost (19,55,62). Some additional disadvantages of nebulizers include cost, the fact that aerosol administration delivered via a range of available nebulizers may require Copyright © 2013 Informa Healthcare USA, Inc

Inhaler devices for patients with COPD


5–20 minutes, depending on the prescribed formulation (47,63), and a requirement for scrupulous cleaning to avoid contamination with micro-organisms (as discussed later in the text). The value of nebulizer therapy was demonstrated in a recent observational study of outpatients with COPD or asthma who were regularly using either inhalers only or both nebulizers and inhalers for home aerosol therapy. Patients using nebulizers were significantly more likely to perform critical errors in using an inhaler than those using inhalers only (64). This observation emphasizes that there is a subgroup of patients who will not be able to use inhalers and who might benefit from nebulizer therapy. Despite several limitations, maintenance therapy with nebulizers is recommended in elderly patients, patients with severe disease and frequent exacerbations, and patients with physical and/or cognitive limitations (65).

Pressurized metered-dose inhalers The introduction of the first portable inhaler device, a pMDI, represented an advance over its antecedent, the traditional nebulizer (Figure 1). Since their introduction in the mid-1950s, pMDIs have been the most frequently prescribed inhaler because they are considered to be effective and convenient for a large percentage of patients (28,66). The reasons for widespread pMDI use relate to their compact size, portability, low cost, ubiquitous availability, lack of requirement for a power source, capacity for delivering repeated consistent drug doses, and short treatment time (67,68). The original pMDIs utilized a mixture of three CFC propellants, which produced a high-velocity plume with a large range of particle sizes. This resulted in relatively low lung (~4–55%) and high oropharyngeal deposition (~30–85%; Table 3). The original CFC pMDIs were affected by ambient temperatures, with significant reduction in propulsion and output in colder weather. Another problem with CFC pMDIs was the ‘tail-off ’ phenomenon. As the pMDI emptied, two problems could emerge. The amount of propellant in each dose could vary substantially, some aerosol sprays having little propellant and others having almost the normal amount. Also, the individual aerosol sprays might contain only propellant. Consequently a patient unknowingly might continue to use the pMDI long after it was “empty” (67). To assist patients in determining when their CFC pMDI might be “empty,” many healthcare providers have recommended the “float test.” In this test, the pMDI is put in water; an empty canister should float, while a full (heavier) canister should sink. Unfortunately, the “float test” does not accurately determine remaining drug content in the canister. It also might contribute to clogging of the device by allowing water to enter the canister stem (67,69). In the last few years, regulatory agencies have required new pMDIs entering the market to have www.copdjournal.com

integral counting devices, which should clearly indicate to the patient when to replace the inhaler. In 1988, concerns about greenhouse gas emissions led to the adoption of the Montreal Protocol on Substances That Deplete the Ozone Layer, leading to a phase-out of CFCs (25,26). Although pMDIs contributed to < 1% of total CFC use, regulators mandated a phase-out of CFC pMDIs as soon as possible, resulting in a pharmaceutical industry consortium working for 10 years to develop an alternate propellant system, the hydrofluoroalkane (HFA). Unfortunately, the development of HFA propellants for pMDIs has not entirely reduced environmental concerns (28). Although the greenhouse gas potential of HFAs is less than that of CFCs, it is not zero. As the propellant changed, the metering valves, materials, and excipients used in the pMDIs also had to change for the first time in over 45 years. The new HFA pMDIs vary considerably in their performance characteristics. Some have a solution formulation designed to produce finer particles, softer sprays, and be less impacted by changes in temperature. These solution HFA pMDIs with smaller particle sizes result in increased lung deposition (70). Other HFA pMDIs with particle-suspension formulations are considered to be equivalent in efficacy to the CFC pMDIs that they replaced (71,72). Patients using some HFA pMDIs may experience less of a “cold freon” effect, i.e., the cold sensation felt at the back of the throat as the result of evaporating propellants, compared with CFC pMDIs. Curiously, this has resulted in concerns for some patients who have used this cold sensation as an indicator that the inhaler was working. In order to reduce anxiety, considerable efforts were required to inform and reassure patients that HFA pMDIs work properly without producing the cold sensation. An important inhaler requirement is to deliver reproducible drug doses to the patient’s lungs. In pMDIs that contain suspension formulations (all CFC devices and some HFA devices), drug suspended in the formulation will settle out of the suspension over time. This settling effect will affect the performance of the device in two ways. The first effect is to cause dose-to-dose variability in drug content of an individual spray (73,74). The pMDI contains within the valve a metering tank containing the next dose to be administered. A retaining cup is located in series between the metering tank and the canister containing the drug formulation. The retaining cup contains the second dose to be administered. Depending upon the position in which the pMDI is stored, drug in the metering tank may settle out of the suspension (‘cream out’) and leak back into the retaining cup (or vice versa). Because propellant would remain in the metering tank, when the device is fired, the drug content of the spray might be less (or more) than the expected labeled dose. The next dose, which comes from the retaining cup, would then be more (or less) than the expected labeled dose. There would be inconsistent doses on a puff-to-puff basis; however, with the two puffs, the appropriate labeled dose would be administered. The

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second way that the suspension formulation affects device performance is the drug content in the formulation within the canister. After each device actuation, the drug formulation within the canister refills the retaining cup. If drug settles out of suspension, the formulation entering the retaining cup might have more (or less) drug. To eliminate this problem, patients are advised to shake the pMDI to re-suspend the drug in formulation within the canister. A major issue in effective administration of drug from a pMDI is the coordination of actuation with inhalation (28). Failure of proper hand–breath coordination while using a pMDI will result in greatly reduced doses of drug reaching the lungs. Even with the correct inhaler technique, only a comparably small fraction of the dose delivered by suspension pMDIs actually reaches the lungs. The newer HFA solution pMDI sprays (with small drug particles) are able to penetrate deeper into the airways (75), and one such device has been shown to deliver a high and homogeneous lung deposition in normal subjects and in patients with respiratory disease (76). Accessory devices such as spacers and valved holding chambers (which should also be regularly cleaned for optimal performance) do provide an advantage to pMDI use by reducing oropharyngeal deposition. They also may minimize the requirement for the precise coordination of actuation–inhalation in the “press-and-breathe” technique used for traditional pMDIs (28). Valved holding chambers added to the pMDIs reduce aerosol loss when inhalation is delayed, and may increase the inhaled dose by more than 4-fold (77). Deposition studies with the newer HFA solution pMDIs have shown that these accessory devices might improve lung deposition in children below the age of 11 but do not increase lung deposition in older children and adults (78,79). The advantages of such accessory devices are offset by the added size, complexity, and cost (28,29). Breath-actuated, and velocity-modifying inhalers (producing softer and more efficiently delivered spray) represent user-friendly alternatives to traditional pMDIs (68). Omission or improper execution of any inhalation step (per device-specific inhaler instructions) constitutes poor technique, e.g., as reported for 8–59% of pMDI users (80,81) or 4–94% of DPI users (57,82–86) with respiratory disease, which can result in little or no pulmonary drug deposition. In studies of patients with COPD in primary care, about 24–67% of individuals made errors in their pMDI use that affected treatment (87–89). The absolute requirement for a proper “pressand-breathe” technique to achieve appropriate pulmonary drug deposition by a traditional pMDI may be beyond the abilities of some elderly patients (28).

multi-dose drug reservoirs and multiple blister packs. Breath actuation of DPIs has eliminated some of the coordination problems experienced by patients using traditional pMDIs. The use of a highly stable, dry, drug powder formulation, available in single- and multidose drug blister packs, non-irritating excipients, and improved inhaler designs, have made these devices more widely acceptable (55). Drugs contained in the DPIs are often formulated as respirable small particles (0.5–5 μm) mixed in a loose aggregate with larger carrier particles (e.g., glucose or lactose). When inhaling from commonly used DPIs (Table 1), the drug and carrier are released from the capsule or blister pack, and the small particles separate or disaggregate from the carrier. Incomplete disaggregation of small particles from the lactose carrier, though, will result in larger inhaled particle sizes and oropharyngeal deposition up to 80% of the label dose (21). Depending on the device, inspiratory flow generates the energy to draw the powder from the container, and disaggregate and lower than optimal flows can result in substantial reductions of inhaled dose. The typical DPI is a passive device (i.e., relying on patient inspiratory effort). Even when used by patients with an optimal technique that generates an acceptable PIF (Table 4) (90,91), these devices still only achieve 10–40% pulmonary drug deposition with up to 80% oropharyngeal deposition. Under ideal circumstances, DPIs should enable consistent delivery of a monodisperse aerosol that can penetrate deeply into the lungs at high drug deposition concentrations (28,92). Improper usage, storage, or exposure to moisture can affect the dry drug powder and ultimately the emission of stable and reproducible drug aerosols from the device (28). When used properly, a DPI can deliver drug particles effectively to the lungs of patients with respiratory disease (48). However, correct use of one brand of DPI does not guarantee correct use of a different brand, because each device has different characteristics and handling requirements. Study data showed that 4–94% of patients misuse a DPI depending on the type of device and method of assessment used (57,82–86). In one study, inhaler-specific error rates were shown to range from 9.1–53.1% with DPIs in patients with varying degrees of airflow limitation (57), although it is not known whether this misuse would impact the therapeutic efficacy of the

Table 4. Suitability of commonly used portable inhalers based on patient inhalation capabilities (90,91) Devices

Good PIF > 30 L/min

pMDI

Yes

pMDI + VHC

DPI

Yes

DPI (limited to low flow design, eg, HandiHaler®)

SMI

Yes

Yes

Dry powder inhalers The DPIs represent a major alternative to pMDIs and have evolved from simple, single-dose devices requiring a mechanism to pierce drug capsules to units containing

Poor PIF < 30 L/min

PIF = peak inspiratory flow rate, pMDI = pressurized metered-dose inhaler, DPI = dry powder inhaler, SMI = Soft Mist inhaler, VHC = valved holding chamber.

Copyright © 2013 Informa Healthcare USA, Inc



devices. The error rates were higher with increasing age and severity of airway obstruction (p3 days

albuterol

Proventil® HFA

4

>14 days

Ventolin® HFA

4

>2 weeks

ProAir® HFA

3

>2 weeks

Atrovent® HFA

2

>3 days

Combivent® CFCb

3

1 day

Respimat® SMIc

1d

SAACs: ipratropium SABA/SAAC combination: ipratropium + albuterol LAACs: tiotropium

LABA/ICS combinations: fluticasone + salmeterol

Advair® HFA

4

budesonide + formoterol

Symbicort® HFA

2

>7 days >4 weeks with 2 primes for HFA; Reprime if canister is dropped >7 days or when canister has been dropped

a Brand new inhalers may also have to be primed prior to first use as per manufacturer instructions. b U.S. Food and Drug Administration recommendations to discontinue inhaler by December 31, 2013 per The Montreal Protocol on Substances That Deplete the Ozone Layer (25). c Only available in Europe. d Four actuations prior to first use and full priming after 21 days of no use; fenoterol + ipratropium and albuterol + ipratropium combinations also formulated for this inhaler. SABA = short-acting β2-agonist, HFA = hydrofluoroalkanes, SAAC = short-acting anticholinergic, CFC = chlorofluorocarbons, LAAC = long-acting anticholinergic, SMI = Soft Mist inhaler, LABA = long-acting β2-agonist, ICS = inhaled corticosteroid.

Depending on inhaler device type, several different inhalation errors are possible, including: i) failure to remove the cap; ii) incorrect loading of the dose; iii) failure to pierce the drug capsule; iv) failure to seal the mouthpiece with lips; v) inverting the inhaler; vi) expiration instead of inhalation; vii) improper ‘press-andbreathe’ technique; and viii) sluggish inhalation (28,29). To help minimize the chances of such errors, healthcare providers should: i) build a rapport with patients; ii) Table 6. Considerations for device selection (55) •

Device/drug availability

•

Clinical setting and environment

•

Patient age and ability to use the device correctly

•

Device use with multiple medications

•

Cost and reimbursement

•

Drug administration time

•

Convenience in both acute and outpatient setting

•

Physician and patient preference

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try to understand all parties’ experiences and expectations regarding prescribed pharmacotherapies; iii) be aware of potential treatment issues and provide education (including inhaler training) congruent with patient understanding and ability; and iv) follow up with patients and hone their inhalation skills through reinforced training (108). In addition, multiple inhaler prescriptions can be a source of confusion, especially if drug formulations are housed in canisters belonging to different device classes (109). The availability of different medications in the same inhaler may need to be considered, because having to master several different inhaler techniques may be confusing for patients and lead to poor inhaler technique (109).


Patient preferences and inhaler device selection Although it is impossible to single out any one devicespecific factor that may improve correct use because of the unique needs of each patient with COPD, patient preferences also play a role. These preferences may be because of a perceived efficacy of the device by the patient, ability to use a given inhaler easily, and psychological or physical issues. In the latter case, comorbidities such as neuromuscular disorders and arthritis can impact inhaler technique (110). Despite the advantages of pMDIs and DPIs over wet nebulizers, it remains a fact that elderly patients may show a preference for nebulizers (although these are often used in acute, hospital settings) with regard to perceived effectiveness over other inhaler devices (111,112). In some instances, preferences for a nebulizer may reflect psychological issues, the fact that the patient is usually obliged to rest during a nebulizer treatment, or they may have problems with correct use of a pMDI, DPI, or SMI. Although there was no substantial difference between the effects of drugs delivered via a pMDI and a jet nebulizer to elderly patients with respiratory disease, most patients in a 2-week comparative study considered the nebulizer to be more effective (111). Another report showed that some patients preferred a breath-actuated pMDI (41) versus comparator inhalers, while a separate study indicated a preference for the Respimat SMI inhaler compared with a pMDI (113). On the other hand, ease of use may be one of the explanations why the Genuair® DPI was preferred relative to the Diskus® DPI, HandiHaler DPI, and Respimat SMI among 48 patients diagnosed with COPD, chronic bronchitis, or emphysema (114). Some patients with COPD may prefer multidose devices (115), yet others find that single-dose DPIs are easier to remember, especially if the medication is required only once per day. In another report of experienced inhaler users with COPD naïve to the study devices, patients preferred the Diskus DPI to the HandiHaler DPI (116). Patient preference seemed to correlate with the ability to use a given DPI properly, www.copdjournal.com

based on a separate study of the handling of different DPIs and preferences among patients with respiratory disease (86). The hypothesis that increased satisfaction and preference with any device will always translate into good adherence to therapy and hence positive benefits in terms of sustained bronchodilation has yet to be confirmed (117); however, choosing a device preferred by the patient because of ease of use, physical or psychosocial reasons, may optimize adherence. Teaching patients has yielded significant improvements in inhaler technique (118). An excellent example of detailed guidelines about how to use the range of approved inhaler devices have been prepared for U.S. patients and care providers by the American College of Chest Physicians and are available on their web site (119). Clinicians need to be aware of these issues and take the time to educate patients about the advantages and disadvantages of the various inhaler devices, so that adherence with therapy can be optimized by selecting the best drug–device combinations for each individual patient.

Declaration of Interest Statement Dr. Fink is an advisor/consultant for Aerogen, Cubist, Novartis, Boehringer Ingelheim, Aridis, KaloBios, and Dance. Dr. Colice is a speaker/advisor/consultant for GlaxoSmithKline, Schering-Plough, Merck, Almirall, Skye, MedImmune, Asubio, Boehringer Ingelheim/ Pfizer, and Dey. Dr. Hodder received consulting and speaking honoraria, and research funding from several pharmaceutical companies including Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Nycomed, and Novartis. This article was developed on the basis of the authors’ presentations and discussions at the “Implications of Inhalation Delivery Systems for COPD Therapies” Advisory Board held in New York, NY March 25–26, 2009. This meeting, the authors’ participation, and manuscript preparation were supported financially by Boehringer Ingelheim Pharmaceuticals Inc. and Pfizer Inc. Medical writing assistance was provided by Gill Sperrin CMPP CBiol MSB and Jane Gilbert, BSc of Envision Scientific Solutions during the preparation of this review. Boehringer Ingelheim was given the opportunity to check the data used in the manuscript for factual accuracy only. The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development and have approved the final version of the review that reflects the authors’ interpretation and conclusions.

References 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. 2011, December. http://www.goldcopd.org (accessed 2012, June 29).

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Notice of Correction: This is a slightly altered version of a manuscript previously published early online.

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