Focus on COPD
A Peer-Reviewed Newsletter – Issue 3
July 2011

Devices for Aerosol Delivery in the Treatment of Adults With Asthma and Chronic Obstructive Pulmonary Disease (COPD) in the United States

Rosemary J. Young, APRN, FNP

Rosemary J. Young,
APRN, FNP

Clinical Research Coordinator
Boys Town National Research Hospital

Kevin R. Murphy, MD

Kevin R. Murphy, MD

Director of Allergy, Asthma, and Pulmonary Research
Boys Town National Research Hospital

Department of Pediatrics
University of Nebraska Medical Center

Creighton University School of Medicine

Key Points

  • Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease.
  • All devices for the delivery of aerosolized therapies are effective if used correctly.
  • The availability of the needed medication in a given device, patient preference, and patient abilities should guide device selection.
  • Device training should be provided or arranged by the health care practitioner when a new therapy is prescribed.
  • Health care practitioners should ask patients to demonstrate the use of their inhalers at each visit to validate the appropriate use of the prescribed delivery device correctly.

Other articles in this e-newsletter series:
Review of the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological Management of Chronic Obstructive Pulmonary Disease
Available at: http://advanceweb.com/web/focus_on_copd/article2.html
Reversibility of Airflow Obstruction in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Available at: http://advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction/focus_on_copd_issue2.html
Devices for Aerosol Delivery in the Treatment of Adults With Asthma and Chronic Obstructive Pulmonary Disease (COPD) in the United States
Available at: http://advanceweb.com/web/AstraZeneca/focus_on_copd_issue3_DevicesForAerosol/focus_on_copd_issue3.html

Introduction

Inhaled therapy is the preferred treatment for patients with asthma [1] and chronic obstructive pulmonary disease (COPD) [2] because it allows for the selective delivery of medications to the lungs, thereby potentially avoiding adverse effects of systemic drug exposure. The same classes of inhaled medications are used to treat asthma and COPD and address either airflow restriction or chronic inflammation, which are central features of both diseases [1,2]. Distinct stepwise therapy guidelines are recommended for each disease (see http://advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction/focus_on_copd_issue2.html [an earlier newsletter in this series] for COPD and http://nurse-practitioners-and-physician-assistants.advanceweb.com/Article/The-2007-NHLBI-Guidelines-for-Asthma-Treatment.aspx for asthma) [1,2]. Inhaled long-acting bronchodilators (eg, long-acting β2-adrenergic agonists [LABAs] and long-acting anticholinergic agents) and inhaled corticosteroids (ICSs) are the current mainstays of maintenance therapy for disease control in COPD [2] and asthma, respectively [1]. The combination of an ICS/LABA is recommended for patients with COPD who have severe or very severe disease and a history of exacerbations [2] and for patients with asthma whose disease is not adequately controlled on a long-term asthma control medication (such as an ICS) or whose disease severity clearly warrants initiation of treatment with both an ICS and a LABA [1]. ICS monotherapy is indicated only for asthma, whereas short- and long-acting anticholinergic agents for the treatment of bronchospasm and LABA monotherapy are indicated only for COPD. Use of a LABA without the use of a long-term control medication is contraindicated in patients with asthma [3]. Selecting the correct combination of drug therapy and inhalation device can be challenging. This newsletter provides an overview of several delivery devices available for inhaled asthma and COPD treatments in the United States to assist health care providers in selecting the most appropriate drug/device combination for adult patients.

Device Selection

Despite the perception that patients with COPD have minimally reversible airflow obstruction, evidence from clinical studies suggests that they can have a significant bronchodilator response. The devices commonly used to deliver inhaled medications to adult patients with asthma and COPD in the United States include pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulizers (Table 1). Provided that the device is used correctly, the type of device has no significant effect on the efficacy of inhaled therapy in patients with COPD or asthma [4,5]. The availability of the desired medication in a specific device and patient preference should guide drug/device selection [6]. Each device has advantages and disadvantages that may influence device selection (Table 2). Health care providers must make sure that the patient is able to use the device correctly to enable successful treatment outcomes. Dose counters are now featured on many inhalers so patients can keep track of dispensed doses and know when medication is running out.

Table 1. Aerosol Delivery Devices Used for the Treatment of Adults With Asthma or COPD in the United States

Generic Drug Name Device Type Indication Age Indication Product Trade Name Minimum Inspiratory Flow Rate US Prescribing Information
SABA
Albuterol sulfate pMDI Bronchospasm (ROAD)

Prevention of EIB
≥ 4 years ProAir® HFA N/A Download PDFa
Proventil® HFA N/A Download PDFa
Ventolin®
HFA
N/A Download PDFa
Levalbuterol tartrate pMDI Bronchospasm (ROAD) ≥ 4 years Xopenex® HFA N/A Download PDFa
Levalbuterol HCl Nebulizer Bronchospasm (ROAD) ≥ 6 years Xopenex®
Inhalation Solution
N/A Download PDFa
Metaproterenol sulfate Nebulizer Bronchospasm
(Asthma/COPD)
≥ 12 years Alupent® N/A Download PDFa
Pirbuterol acetate Breath-activated pMDI Bronchospasm ≥ 12 years Maxair®
Autohaler®b
N/A Download PDFa
LABA
Arformoterol tartrate Nebulizer COPD Adultsc Brovana® Inhalation Solution N/A Download PDFa
Formoterol fumarate DPI Asthma (with concomitant controller) ≥ 5 years Foradil® Aerolizer® 60 L/min Download PDFa
Prevention of EIB ≥ 5 years
COPD Adults
Nebulizer COPD Adultsc Perforomist® Inhalation Solution N/A Download PDFa
Salmeterol xinafoate DPI Asthma (with concomitant controller) ≥ 4 years
Serevent® Diskus® 60 L/min Download PDFa
Prevention of
EIB
≥ 4 years
COPD Adults
ICS
Budesonide DPI Asthma ≥ 6 years Pulmicort Flexhaler™ 60 L/min Download PDFa
Fluticasone propionate pMDI Asthma ≥ 4 years Flovent®
HFA
N/A Download PDFa
DPI Asthma ≥ 4 years Flovent®
Diskus®
60 L/min Download PDFa
Mometasone furoate DPI Asthma ≥ 4 years Asmanex®
Twisthaler®
30 L/min Download PDFa
ICS/LABA
Budesonide/formoterol fumarate dihydrate pMDI Asthma ≥ 12 years Symbicort® Inhalation Aerosol N/A Download PDFa
COPD
Adults
Fluticasone propionate/salmeterol pMDI Asthma ≥ 12 years Advair®
HFA
N/A Download PDFa
DPI Asthma ≥ 4 years Advair® Diskus®
60 L/min Download PDFa
COPD Adults
Mometasone furoate/formoterol fumarate dihydrate pMDI Asthma ≥ 12 years Dulera® N/A Download PDFd
Short-acting anticholinergic
Ipratropium bromide pMDI COPD Adults Atrovent®
HFA
N/A Download PDFa
Short-acting anticholinergic/SABA
Ipratropium bromide
and albuterol sulfate
Nebulizer COPD Adults DuoNeb® Inhalation Solution N/A Visit sitea
pMDI COPD Adults Combivent® Inhalation Aerosolb N/A Download PDFe
Long-acting anticholinergic
Tiotropium bromide DPI COPD Adults Spiriva®
Handihaler®
20 L/min Download PDFa

aPrescribing information accessed December 14, 2010.
bChlorofluorocarbon inhaler scheduled to be phased out of production by December 31, 2013 [8].
cSafety and effectiveness have not been established in pediatric patients.
dPrescribing information accessed February 4, 2011.
ePrescribing information accessed March 14, 2011.

COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; EIB, exercise-induced bronchospasm; HCl, hydrochloride; HFA, hydrofluoroalkane; ICS, inhaled corticosteroid; LABA, long-acting β2-adrenerigic agonist; N/A, not applicable; pMDI, pressurized metered-dose inhaler; ROAD, reversible obstructive airways disease; SABA, short-acting β2-adrenerigic agonist.

Table 2. Advantages and Disadvantages of Commonly Used Aerosol Delivery Devices [4,6]

Populationa Advantage Disadvantage
pMDI
  • Aged ≥ 5 years (< 5 years with a spacer or valved holding chamber)
  • Portable and compact
  • Can be used quickly
  • No preparation of drug required
  • No contamination of contents
  • Must be able to coordinate actuation and inhalation
  • High pharyngeal deposition
  • Upper limit to unit dose content
Breath-actuated MDI
  • Aged ≥ 5 years
  • Appropriate for patients unable to coordinate inhalation and actuation
  • May particularly be useful in the elderly
  • Less variation in emitted dose because of reproducible actuation
  • Patients may incorrectly stop inhalation at actuation
  • Cannot be used with available spacer/valved holding chamber devices
DPI
  • Aged ≥ 4 years
  • Breath actuated
  • Less patient coordination required compared with a pMDI device
  • No need for propellant
  • Portable and compact
  • Can be used quickly
  • No preparation of drug required
  • Some units are single dose
  • Loss of dose if patient exhales through the device
  • Can result in high pharyngeal deposition
  • Upper limit to unit dose content
Nebulizers
  • Patients of any age who cannot use a DPI or pMDI with a valved holding chamber and a face mask
  • Patient coordination not required
  • Effective with tidal breathing
  • May be able to administer multiple medications
  • Dose modification is possible
  • May be used at any age
  • Limited portability (jet nebulizers)
  • Longer treatment times (~5–15 minutes)
  • Device cleaning required and contamination possible
  • Lack of availability of some medications in a preparation that can be nebulized
  • Medications may not be compatible with all nebulizer types
  • Variability of performance efficiency among different nebulizers
  • Less efficient than other devices (wasted drug)
  • May be expensive, depending on type
  • If using face mask, must fit appropriately

aPopulation recommendations are based on Figure 3-24 of the 2007 National Asthma Education and Prevention Program Expert Panel Report 3 [1]; however, patient coordination, preference, and ability should all be taken into consideration when prescribing the appropriate delivery device.

DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler.

Reproduced with permission from the American Association for Respiratory Care [4].

pMDIs

The pMDIs are convenient devices that use a propellant for the delivery of metered doses of aerosolized medication [7]. To address environmental concerns, hydrofluoroalkane, which has no ozone-depleting properties, has replaced chlorofluorocarbon (CFC) as the propellant in pMDIs [7]. The CFC inhalers for flunisolide, triamcinolone, metaproterenol, and the combination of albuterol and ipratropium have been or will soon be phased out of production [8]; most inhaler products have been reformulated as hydrofluoroalkane pMDIs. The pMDIs are portable and can be used without preparation, but their use requires proper coordination of inhalation and device actuation – the patient has to be able to press the canister while simultaneously inhaling (Table 2) [4]. Elderly patients and patients with poor mental/cognitive status, diminished manual dexterity, or both may have difficulty properly using a pMDI [9]. However, this limitation usually can be circumvented by attaching a spacer to the end of the pMDI [4].

Spacers for Use With pMDIs

Open-tube spacers, valved holding chambers, and reverse-flow devices (eg, collapsible bag) are three categories of spacer devices [10] that slow pMDI aerosol spray velocity, thus reducing oropharyngeal deposition when used correctly [6]. Advantages of spacer use include improved ease of pMDI use and pulmonary drug delivery [6]. Some patients may find the pMDI/spacer combination to be complicated, and if the patient waits too long to inhale from the pMDI/spacer, delivery of the drug to the lungs may be reduced [4,6]. Use of spacers/holding chambers with a pMDI may increase expense (spacers may not be covered by commercial insurance) and decrease portability [4].

Breath-actuated MDIs have been developed to overcome the problem of coordinating inhalation with device actuation and are not used with spacers [4,6]. Maxair® Autohaler® (Graceway Pharmaceuticals, LLC, Bristol, TN) for the delivery of the short-acting bronchodilator pirbuterol is the only breath-actuated MDI product available in the United States [4]. Because the product includes a CFC propellant, it will be out of production in 2014 [8].

DPIs

The DPIs, which are breath-activated, were developed to eliminate the need for coordinating inhalation and device actuation [11,12] and do not require a propellant for aerosol delivery [11]. Instead, micronized drug is mixed with carrier particles within a dry powder bed. When a patient inhales, the force of airflow fluidizes and disperses the dry powder aerosol [13]. Therefore, drug delivery from a DPI depends on a patient’s peak inspiratory flow rate—how rapidly and forcefully the patient can inhale. Specific DPI devices may not be effective for use in patients with COPD with severely reduced lung function [12] or in those experiencing acute asthma attacks [4]. If concerned about technique, or that the patient’s respiratory status is not adequately controlled, testers such as the In-Check™ DIAL device (Alliance Tech Medical, Inc., Granbury, TX; www.alliancetechmedical.com) may be beneficial to ensure that the patient can generate sufficient inspiratory force.

The DPIs are portable and do not require hand–breath coordination or spacers. However, DPIs carry a risk of dose loss if a patient inadvertently exhales into the DPI [7] and DPIs are sensitive to humidity [9]. Several different types of DPIs for single or multiple dosing are available [7]. For single-dose systems, a powder-filled capsule must be inserted into the device before each use (eg, tiotropium DPI [Spiriva® HandiHaler®; Boehringer Ingelheim, Inc., Ridgefield, CT); therefore, it is important to assess the patient’s ability to manipulate the small capsules before prescribing these devices. Multidose DPIs are available for administration of ICS and ICS/LABA therapy.

Nebulizers

Despite the perception that patients with COPD have minimally reversible airflow obstruction, evidence from clinical studies suggests that they can have a significant bronchodilator response.Nebulizers can be used effectively by all patients because they do not require specialized inhalation techniques [7]. Jet, ultrasonic, and vibrating mesh nebulizers use different mechanisms (eg, driven by compressed air, high-frequency vibrating crystals, and vibrating meshes or plates, respectively [7]) to create a mist that is inhaled through a tube-like mouthpiece or face mask. Most nebulized medications are available as unit doses, premixed solutions that can be emptied directly into the nebulizer cup. However, some nebulized medications are concentrated solutions that require saline dilution before use, which is an important teaching point for patients using nebulized medications. Therapies may not be compatible with all nebulizer types; for example, medication suspensions are not delivered efficiently from vibrating mesh [14] or ultrasonic nebulizer systems [7,14]. Nebulizers are associated with longer treatment times (eg, approximately 5 to 15 minutes) than pMDIs and DPIs and require maintenance to prevent contamination. It is important to clean nebulizers (and other devices) routinely. Newer devices are battery operated and more portable than older models.

Nebulizers are most appropriate for patients unable to use other devices (Table 2) [6] and may be used in addition to a pMDI in elderly patients with COPD [15]. Findings from a study of patients with COPD who were older than 50 years and who used albuterol and ipratropium showed that nebulizer use in the morning and evening, coupled with pMDI use during the mid day (ie, when patients were away from home) provided greater quality of life benefits than use of an inhaler alone [15]. For asthma, large-volume nebulizers are ideal for the continuous delivery of short-acting bronchodilators in an emergency setting to patients having an acute attack [7].

What Drugs Are Available for Which Device?

PullquoteMost inhaled treatments for asthma and COPD are available in the United States in more than 1 type of delivery device (Table 1). Short-acting β2-adrenergic antagonists (SABAs) are available as pMDIs and as solutions for nebulizer use but not as DPIs. Because pMDIs are portable, relatively inexpensive, and can be used quickly in emergency situations, they are appropriate for most adults who require easy access to their rescue medication. For patients with COPD, ipratropium, a short-acting anticholinergic, can be taken as monotherapy with a pMDI or in combination with albuterol (a SABA) via pMDI or nebulizer. For the delivery of long-acting bronchodilators and ICS therapy, device portability is less important than other product features because these therapies are used for maintenance, not rescue, therapy. Depending on the specific medication, LABAs are available as DPIs or solutions for nebulizer use, whereas ICS monotherapy and ICS/LABA combination therapy are available in DPIs and pMDIs.

Ensuring Correct Device Use

PullquoteImproper use of delivery devices, which may reduce the clinical efficacy of therapy, appears to be widespread [9]. Cognitive inability to reliably follow instructions precisely and physical limitations, such as reduced lung function and poor hand strength or finger dexterity [9,12], may reduce the effectiveness of inhalation devices in some patients (eg, elderly patients with asthma or COPD). Proper education and training are crucial to ensure that patients use inhaler devices correctly.

Tables 3 and 4 summarize the necessary steps for the correct use of pMDIs and DPIs and the severity of the clinical consequence of misuse. Tailored education and instruction are essential for correct use, given differences in product design and maintenance among the devices in the same category [9]. Specific details are available in the prescribing information for each product, but health care providers also should explain and demonstrate proper use, observe patients using their inhalers, spacers, and nebulizers at each visit, and correct technique if necessary [11]. Health care providers also should assess patient comfort with the device and determine if there are any issues with obtaining the device (eg, cost, insurance coverage). Practitioners also may want to consider prescribing the same device type for all medications if feasible (eg, pMDI for rescue and maintenance therapy).

Table 3. Steps for Correct Use of a pMDI and Consequences of Incorrect Use

Recommended Technique for pMDI Use Consequences of Incorrect Use
Remove cap from the mouthpiece Serious (ie, critical error)
Shake inhaler immediately before use Minor
Empty lungs completely or almost completely before spray activation Minor
Place mouthpiece in the mouth with lips sealed around it and avoiding any flow obstruction with the tongue or, alternatively, approximately 3–4 cm in front of the wide open mouth Minor to serious
Keep the spray with the longest part pointing upwards during delivery Minor
Activate the inhaler only once for a single inhalation Minor
Activate the inhaler during the first half of inhalation Moderate to serious
Slowly inhale during activation Moderate
Continue to fill lungs completely and without interruption after delivery of the dose Moderate
Hold breath for at least 8–10 seconds and as long as possible after inhalation is complete Moderate

pMDI, pressurized metered-dose inhaler.

Adapted with permission of the publisher Mattioli 1885 spa from Melani AS. Inhalation therapy training: a priority challenge for the physician. Acta Biomed. 2007;78:233-245 [11].

Table 4. Steps for Correct Use of a Multidose DPI and Consequences of Incorrect Use

Recommended Technique for DPI Use Consequences of Incorrect Use
Remove inhaler cap/open dispenser Serious (ie, critical error)
Load dispenser sufficiently Serious
Empty the lungs, avoid exhaling into the inhaler after loading Moderate
Place the mouthpiece in the mouth, with lips sealed around it and avoiding any obstruction with the tongue Minor to serious
Inhale with maximum force from the start Minor to serious
Stop inhalation only after the lungs are filled completely Minor
Remove the inhaler from the mouth without exhaling into it Minor
Close the inhaler Minor

DPI, dry powder inhaler.

Adapted with permission of the publisher Mattioli 1885 spa from Melani AS. Inhalation therapy training: a priority challenge for the physician. Acta Biomed. 2007;78:233-245 [11].

Office tools are available to help health care providers teach patients to use devices correctly. Posters and other materials with pictures of respiratory inhalers are available from organizations such as the Allergy & Asthma Network Mothers of Asthmatics (http://www.aanma.org). The National Asthma Education and Prevention Program’s Expert Panel Report 3 on the Guidelines for the Diagnosis and Management of Asthma Committee provides a patient instruction sheet for pMDI use (http://www.nhlbi.nih.gov/guidelines/asthma/05_sec3_comp2.pdf, see Figure 3-14). National Jewish Health provides detailed instructions, including photographs and instructional videos, for correct use of devices and spacers (http://www.nationaljewish.org/healthinfo/medications/lung-diseases/devices/index.aspx).

Summary

Inhaled therapy is central to the treatment of asthma and COPD. Each device for delivery of inhaled medications, including pMDIs, DPIs, and nebulizers, has advantages and disadvantages and should be selected carefully. To ensure that patients use prescribed delivery devices correctly, health care providers should provide appropriate instruction for the proper techniques and regularly verify correct use.

Acknowledgements

We thank Marissa Buttaro, MPH, RPh, Roland Tacke, PhD, and Kristen Quinn, PhD, from Scientific Connexions (Newtown, PA), who provided medical writing support funded by AstraZeneca LP (Wilmington, DE).

Other articles in this e-newsletter series:
Review of the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological Management of Chronic Obstructive Pulmonary Disease
Available at: http://advanceweb.com/web/focus_on_copd/article2.html
Reversibility of Airflow Obstruction in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Available at: http://advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction/focus_on_copd_issue2.html
Devices for Aerosol Delivery in the Treatment of Adults With Asthma and Chronic Obstructive Pulmonary Disease (COPD) in the United States
Available at: http://advanceweb.com/web/AstraZeneca/focus_on_copd_issue3_DevicesForAerosol/focus_on_copd_issue3.html

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