Download Inhaler Technology—Improving Prevention and Reversal of

Basset_edit.qxp
1/8/08
10:53
Page 10
Asthma
Inhaler Technology—Improving Prevention and Reversal of Bronchospasm
a report by
C l i f f o rd W B a s s e t t , M D , FA A A A I , FAC A A I 1 and R a f a e l E d e l a H o z , M D , M P H 2
1. Medical Director, Allergy and Asthma Care of New York, Assistant Clinical Professor of Medicine and Otolaryngology, The Long Island College Hospital, and Faculty,
New York University School of Medicine; 2. Assistant Professor, Department of Community and Preventive Medicine, Mount Sinai School of Medicine
Bronchospasm is most commonly the result of asthma and chronic
obstructive pulmonary disease (COPD). However, the disease can also be
caused by anaphylactic shock or other chronic lung diseases. Asthma affects
16.1 million adults and an estimated 6.8 million children in the US1,2 and is
clearly a major public health problem. Asthma-related direct and indirect
medical costs exceed $12 billion.3 COPD is the fourth leading cause of death
and affects an estimated one in 20 adults in the US.1,4 Thus, improving
care through better physician and patient education, adding to the
understanding of the diseases, and the development of new technologies
will help to reduce the burden of asthma and COPD.
Current Treatment Options
Rescue therapy is generally first-line treatment for relieving acute
bronchospasm associated with asthma and COPD. Rescue therapies are
usually fast-response, short-acting medications administered through
the inhalation route to maximize therapeutic effect and limit the
number of adverse events.5 The aim of inhalation therapy is to reverse
and minimize symptoms by delivering low doses of medication directly
to the smooth muscle in the airways. There is a broad range of inhaler
devices available, but many patients still use inhalers suboptimally. Thus,
it is important that the device chosen for the patient can be used
correctly and beneficially.
Clifford W Bassett, MD, FACAAI, FAAAAI, is Medical Director
of Allergy and Asthma Care of New York, an Attending in
Allergy and Immunology at The Long Island College Hospital
in Brooklyn, on the Faculty of New York University School of
Medicine, and a Clinical Assistant Professor of Medicine and
Otolaryngology at the State University of New York-Health
Sciences Center at Brooklyn. He is a diplomate of the
American Board of Allergy and Immunology and a Fellow of
the American College and the American Academy of Allergy.
He is Vice Chair of the Public Education committee of the American Academy of Allergy,
Asthma and Immunology (AAAAI) and served on the National Anaphylaxis Task Force for the
AAAAI. As an investigator in clinical trials, Dr Bassett has published papers in the Journal of
Allergy and Clinical Immunology, Annals of Allergy, Pediatrics, and Chest. He is an expert on
seasonal/indoor allergies, allergic skin disorders, asthma, pollen counting, exercise asthma, pet
allergies, food allergies, and allergic emergencies.
E: [email protected]
Rafael E de la Hoz, MD, MPH, is an Assistant Professor in the Department of Community and
Preventive Medicine at Mount Sinai School of Medicine in New York, and also Assistant Medical
Director of the Mount Sinai World Trade Center Monitoring and Treatment Program. His primary
clinical and research interests are pulmonary and occupational medicine.
10
Currently, there are two main drug classes of inhaled medication:
bronchodilators and corticosteroids. Bronchodilators include short- and
long-acting beta agonists and antimuscarinic drugs, which all act to reduce
symptoms of bronchoconstriction. Corticosteroids are administered to
reduce inflammation of the airways and to prevent the symptoms of asthma
and COPD. For the purpose of this article, the focus will be on the use
and delivery of short-acting beta agonists as a rescue medication.
Short-acting Beta Agonists
Several types of short-acting beta agonists (SABAs) are prescribed to
patients with COPD and asthma, including albuterol, levalbuterol,
metaproterenol sulphate, and pirbuterol acetate. The SABAs albuterol,
levalbuterol, and pirbuterol acetate remain the cornerstone of rescue
therapy for the prevention of exercise-induced bronchospasm (EIB).5 It is
important to note that SABAs are not recommended for regularly
scheduled, daily, long-term use.5 It is not within the scope of this article to
provide an in-depth review of the current clinical evidence for SABAs in the
treatment of acute symptoms, but a number of extensive reviews and
guidelines have been published.5–11
In general, the selective SABAs albuterol, levalbuterol, and pirbuterol are
comparable in efficacy on a per-puff basis. These SABAs also have few
systemic and cardiovascular adverse effects, although care should be taken
in patients with pre-existing cardiovascular disease, including ischemic heart
disease, hypertension, or cardiac arrhythmias.5
Albuterol is a widely prescribed SABA. Several studies have shown that
levalbuterol is safe and efficacious, and has similar effects on forced
expiratory volume in one second (FEV1) to albuterol.12–15 Pirbuterol has also
been used successfully as a drug taken when needed.16
Inhalation Devices
There are a wide variety of inhalation devices available to patients. The
most universally used and cheapest inhalation device is the conventional
pressurized metered-dose inhaler (pMDI). However, evidence suggests
that up to 75% of patients use traditional pMDIs incorrectly and that
even after re-training roughly 50% revert to the wrong technique.17–19
Incorrect use leads to the greatest single limitation of the pMDI:
inconsistent dosing. For ideal drug delivery, the MDI canister should be
depressed at early to mid-inhalation. Unfortunately, hand–breath
asynchrony, the most common form of suboptimal inhaler technique, has
been noted as a particular problem in elderly patients and children.20,21
Incorrect use of pMDIs can also result from excessive inspiratory flow
velocity and nose breathing.
© TOUCH BRIEFINGS 2008
Graceway_ad.qxp
29/7/08
12:41
Page 11
For the prevention and reversal of bronchospasm
THE BENEFITS OF A SPACER
...WITHOUT THE SPACER
1
The only rescue inhaler
that eliminates the need to
coordinate pressing with breathing
(pirbuterol acetate inhalation aerosol)
AVAILABLE
BEYOND 2008
Just breathe in.
Not subject to albuterol
CFC deadline
MAXAIR AUTOHALER is indicated for prevention and reversal of
bronchospasm in patients aged 12 years and older with reversible
bronchospasm including asthma. It may be used with or without
concurrent theophylline and/or corticosteroid therapy.
IMPORTANT SAFETY INFORMATION : MAXAIR AUTOHALER is contraindicated in patients with a history of hypersensitivity to pirbuterol or
any of its ingredients. MAXAIR AUTOHALER, like other inhaled betaadrenergic agonists, can produce a clinically significant cardiovascular
effect in some patients, as measured by pulse rate, blood pressure, and/or
other symptoms. Although such effects are uncommon after
administration of MAXAIR AUTOHALER at recommended doses, if they
occur, the drug may need to be discontinued. In addition, beta-agonists
have been reported to produce ECG changes, such as flattening of the
T wave, prolongation of the QTc interval, and ST segment depression.
The clinical significance of these findings is unknown. Therefore,
MAXAIR AUTOHALER, like all sympathomimetic amines, should be used
with caution in patients with cardiovascular disorders, especially coronary
insufficiency, cardiac arrhythmias, and hypertension.
MAXAIR AUTOHALER can produce paradoxical bronchospasm,
which can be life threatening. If paradoxical bronchospasm occurs,
MAXAIR AUTOHALER should be discontinued immediately and alternative
therapy instituted.It should be recognized that paradoxical bronchospasm,
when associated with inhaled formulations, frequently occurs with the first
use of a new canister or vial.
The use of beta-adrenergic agonist bronchodilators alone may not be
adequate to control asthma in many patients. Early consideration should
be given to adding anti-inflammatory agents, eg, corticosteroids.
The following adverse reactions were reported more frequently than 1 in
100 patients: nervousness (6.9%), tremor (6.0%), headache (2.0%),
dizziness (1.2%), palpitations (1.7%), tachycardia (1.2%), cough (1.2%),
and nausea (1.7%).
Please see accompanying brief summary of full Prescribing Information.
Reference: 1. Grossman J, Tinkelman DG, Ziment I. Pirbuterol acetate administered via breath-actuated
inhaler compared with albuterol administered via MDI with a spacing device. Medscape General Medicine.
1999;1(2). http://www.medscape.com/viewarticle/408722. Accessed February 8, 2008.
www.maxairautohaler.com
©2008 Graceway Pharmaceuticals, LLC, Bristol, TN
MAX030830
Graceway_ad.qxp
29/7/08
12:42
Page 12
MAXAIR® AUTOHALER®
(pirbuterol acetate inhalation aerosol)
For Oral Inhalation Only
Brief Summary of Prescribing Information
See Package Insert for Full Prescribing Information
INDICATIONS AND USAGE MAXAIR AUTOHALER is indicated for the prevention and reversal
of bronchospasm in patients 12 years of age and older with reversible bronchospasm
including asthma. It may be used with or without concurrent theophylline and/or
corticosteroid therapy. CONTRAINDICATIONS MAXAIR AUTOHALER is contraindicated in
patients with a history of hypersensitivity to pirbuterol or any of its ingredients. WARNINGS
Cardiovascular: MAXAIR AUTOHALER, like other inhaled beta adrenergic agonists, can
produce a clinically significant cardiovascular effect in some patients, as measured by pulse
rate, blood pressure and/or symptoms. Although such effects are uncommon after
administration of MAXAIR AUTOHALER at recommended doses, if they occur, the drug may
need to be discontinued. In addition, beta-agonists have been reported to produce ECG
changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment
depression. The clinical significance of these findings is unknown. Therefore, MAXAIR
AUTOHALER, like all sympathomimetic amines, should be used with caution in patients with
cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and
hypertension. Paradoxical Bronchospasm: MAXAIR AUTOHALER can produce paradoxical
bronchospasm, which can be life threatening. If paradoxical bronchospasm occurs, MAXAIR
AUTOHALER should be discontinued immediately and alternative therapy instituted. It should
be recognized that paradoxical bronchospasm, when associated with inhaled formulations,
frequently occurs with the first use of a new canister or vial. Use of Anti-Inflammatory
Agents: The use of beta adrenergic agonist bronchodilators alone may not be adequate
to control asthma in many patients. Early consideration should be given to adding antiinflammatory agents, e.g., corticosteroids. Deterioration of Asthma: Asthma may deteriorate
acutely over a period of hours or chronically over several days or longer. If the patient needs
more doses of MAXAIR AUTOHALER than usual, this may be a marker of destabilization
of asthma and requires reevaluation of the patient and the treatment regimen, giving special
consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
PRECAUTIONS General: Since pirbuterol is a sympathomimetic amine, it should be used
with caution in patients with cardiovascular disorders, including ischemic heart disease,
hypertension, or cardiac arrhythmias, in patients with hyperthyroidism or diabetes mellitus,
and in patients who are unusually responsive to sympathomimetic amines or who have
convulsive disorders. Significant changes in systolic and diastolic blood pressure could be
expected to occur in some patients after use of any beta adrenergic aerosol bronchodilator.
Beta adrenergic agonist medications may produce significant hypokalemia in some patients,
possibly through intracellular shunting, which has the potential to produce adverse
cardiovascular effects. The decrease is usually transient, not requiring supplementation.
Information for Patients: The action of MAXAIR AUTOHALER should last up to five hours or
longer. MAXAIR AUTOHALER should not be used more frequently than recommended. Do
not increase the dose or frequency of MAXAIR AUTOHALER without consulting your physician.
If you find that treatment with MAXAIR AUTOHALER becomes less effective for symptomatic
relief, or your symptoms become worse, and/or you need to use the product more frequently
than usual, you should seek medical attention immediately. While you are using MAXAIR
AUTOHALER, other inhaled drugs and asthma medications should be taken only as directed
by your physician. Common adverse effects include palpitations, chest pain, rapid heart
rate, tremor or nervousness. If you are pregnant or nursing, contact your physician about use
of MAXAIR AUTOHALER. Effective and safe use includes an understanding of the way
the medication should be administered. As with all aerosol medications, it is recommended
to prime (test) MAXAIR AUTOHALER before using for the first time. MAXAIR AUTOHALER
should also be primed if it has not been used in 48 hours. As described in the priming
procedure, use the test fire slide to release two priming sprays into the air away from yourself
and other people. (See “Patient’s Instructions For Use” portion of this package insert.) The
MAXAIR AUTOHALER actuator should not be used with any other inhalation aerosol canister.
In addition, canisters for use with MAXAIR AUTOHALER should not be utilized with any other
actuator. Drug Interactions: Other short-acting beta adrenergic aerosol bronchodilators
should not be used concomitantly with MAXAIR AUTOHALER because they may have additive
effects. Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Pirbuterol should be
administered with extreme caution to patients being treated with monoamine oxidase
inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents,
because the action of pirbuterol on the vascular system may be potentiated. Beta Blockers:
Beta adrenergic receptor blocking agents not only block the pulmonary effect of betaagonists, such as MAXAIR AUTOHALER, but may produce severe bronchospasm in asthmatic
patients. Therefore, patients with asthma should not normally be treated with beta blockers.
However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there
may be no acceptable alternatives to the use of beta adrenergic blocking agents in patients
with asthma. In this setting, cardioselective beta blockers could be considered, although they
should be administered with caution. Diuretics: The ECG changes and/or hypokalemia that
may result from the administration of non-potassium sparing diuretics (such as loop or
thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these
effects is not known, caution is advised in the coadministration of beta-agonists with
non-potassium sparing diuretics. Carcinogenesis, Mutagenesis and Impairment of Fertility: In a 2-year study in Sprague-Dawley rats, pirbuterol hydrochloride
administered at dietary doses of 1.0, 3.0, and 10 mg/kg (approximately 3, 10, and 35 times
the maximum recommended daily inhalation dose for adults and children on a mg/m2 basis)
showed no evidence of carcinogenicity. In an 18-month study in mice at dietary doses of 1.0,
3.0, and 10 mg/kg (approximately 2, 5, and 15 times the maximum recommended daily
inhalation dose for adults and children on a mg/m2 basis) no evidence of tumorigenicity was
seen. Reproduction studies in rats administered pirbuterol hydrochloride at oral doses of 1, 3,
and 10 mg/kg (approximately 3, 10, and 35 times the maximum recommended daily
inhalation dose for adults on a mg/m2 basis) revealed no evidence of impaired fertility.
Pirbuterol dihydrochloride showed no evidence of mutagenicity in in vitro assays and hostmediated microbial (Ames) assays for point mutations and in vivo tests for somatic or germ
cell effects following acute and subchronic treatment in mice (cytogenicity assays).
Teratogenic Effects – Pregnancy Category C: Pirbuterol was not teratogenic in rats
administered oral doses of 30, 100, and 300 mg/kg (approximately 100, 340, and 1000 times
the maximum recommended daily inhalation dose for adults on a mg/m2 basis). Pirbuterol
was not teratogenic in rabbits administered oral doses of 30 and 100 mg/kg (approximately
200 and 680 times the maximum recommended inhalation dose for adults on a mg/m2 basis).
However, pirbuterol at an oral dose of 300 mg/kg (approximately 2000 times the maximum
recommended daily inhalation dose in adults on a mg/m2 basis) caused abortions and fetal
death. There are no adequate and well-controlled studies in pregnant women. Pirbuterol
should be used during pregnancy only if the potential benefit justifies the potential risk to
the fetus. Labor and Delivery: Because of the potential for beta-agonist interference with
uterine contractility, use of MAXAIR AUTOHALER for relief of bronchospasm during labor
should be restricted to those patients in whom the benefits clearly outweigh the risk.
Nursing Mothers: It is not known whether pirbuterol is excreted in human milk. Therefore,
MAXAIR AUTOHALER should be used during nursing only if the potential benefit justifies
the possible risk to the newborn. Pediatric Use: MAXAIR AUTOHALER is not recommended
for patients under the age of 12 years because of insufficient clinical data to establish safety
and effectiveness. ADVERSE REACTIONS The following rates of adverse reactions to
pirbuterol are based on single- and multiple-dose clinical trials involving 761 patients, 400
of whom received multiple doses (mean duration of treatment was 2.5 months and maximum
was 19 months). The following were the adverse reactions reported more frequently than 1
in 100 patients: CNS: nervousness (6.9%), tremor (6.0%), headache (2.0%), dizziness (1.2%).
Cardiovascular: palpitations (1.7%), tachycardia (1.2%). Respiratory: cough (1.2%).
Gastrointestinal: nausea (1.7%). The following adverse reactions occurred less frequently
than 1 in 100 patients and there may be a causal relationship with pirbuterol: CNS:
depression, anxiety, confusion, insomnia, weakness, hyperkinesia, syncope. Cardiovascular:
hypotension, skipped beats, chest pain. Gastrointestinal: dry mouth, glossitis, abdominal
pain/cramps, anorexia, diarrhea, stomatitis, nausea and vomiting. Ear, Nose and Throat:
smell/taste changes, sore throat. Dermatological: rash, pruritus. Other: numbness in
extremities, alopecia, bruising, fatigue, edema, weight gain, flushing. Other adverse reactions
were reported with a frequency of less than 1 in 100 patients but a causal relationship between pirbuterol and the reaction could not be determined: migraine, productive cough,
wheezing, and dermatitis.
The following rates of adverse reactions during three-month controlled clinical trials involving
310 patients are noted. The table does not include mild reactions.
PERCENT OF PATIENTS WITH MODERATE TO SEVERE ADVERSE REACTIONS
Reaction
Pirbuterol
Metaproterenol
N=157
N=153
Central Nervous System
tremors
1.3%
3.3%
nervousness
4.5%
2.6%
headache
1.3%
2.0%
weakness
.0%
1.3%
drowsiness
.0%
0.7%
dizziness
0.6%
.0%
Cardiovascular
palpitations
1.3%
1.3%
tachycardia
1.3%
2.0%
Respiratory
chest pain/tightness
1.3%
.0%
cough
.0%
0.7%
Gastrointestinal
nausea
1.3%
2.0%
diarrhea
1.3%
0.7%
dry mouth
1.3%
1.3%
vomiting
.0%
0.7%
Dermatological
skin reaction
.0%
0.7%
rash
.0%
1.3%
Other
bruising
0.6%
.0%
smell/taste change
0.6%
.0%
backache
.0%
0.7%
fatigue
.0%
0.7%
hoarseness
.0%
0.7%
nasal congestion
.0%
0.7%
Electrocardiograms: Electrocardiograms, obtained during a randomized, double-blind,
cross-over study in 57 patients, showed no observations or findings considered clinically
significant, or related to drug administration. Most electrocardiographic observations,
obtained during a randomized, double-blind, cross-over study in 40 patients, were judged
not clinically significant or related to drug administration. One patient was noted to have some
changes on the one hour postdose electrocardiogram consisting of ST and T wave
abnormality suggesting possible inferior ischemia. This abnormality was not observed on the
predose or the six hours postdose ECG. A treadmill was subsequently performed and all the
findings were normal. OVERDOSAGE The expected symptoms with overdosage are those of
excessive beta-stimulation and/or any of the symptoms listed under ADVERSE REACTIONS,
e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats
per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea,
dizziness, fatigue, malaise, and insomnia. Hypokalemia may also occur. As with all
sympathomimetic aerosol medication, cardiac arrest and even death may be associated with
abuse of MAXAIR AUTOHALER. Treatment consists of discontinuation of pirbuterol together
with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor
blocker may be considered, bearing in mind that such medication can produce
bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for
overdosage. The oral median lethal dose of pirbuterol dihydrochloride in mice and rats is
greater than 2000 mg/kg (approximately 3400 and 6800 times the maximum recommended
daily inhalation dose for adults on a mg/m2 basis).
Note: The indented statement below is required by the Federal government’s Clean Air Act
for all products containing or manufactured with chlorofluorocarbons (CFC’s).
WARNING: Contains trichloromonofluoromethane and dichlorodifluoromethane,
substances which harm public health and environment by destroying ozone in the
upper atmosphere.
A notice similar to the above WARNING has been placed in the “Patient’s Instructions For Use”
portion of this package insert under the Environmental Protection Agency’s (EPA’s)
regulations. The patient’s warning states that the patient should consult his or her physician
if there are questions about alternatives.
This is only a brief summary of important information regarding MAXAIR AUTOHALER. For
more information please visit www.maxairautohaler.com or call 1-800-328-0255.
Rx only
Manufactured by
Distributed by
3M Pharmaceuticals
Graceway™ Pharmaceuticals, LLC
Northridge, CA 91324
Bristol, TN 37620
654800
US19 Rev0407-1
Basset_edit.qxp
1/8/08
10:53
Page 13
Inhaler Technology—Improving Prevention and Reversal of Bronchospasm
Inhalation therapy has recently moved away from the use of
chlorofluorocarbon (CFC)-propelled devices and toward HFA inhalers due to
CFC gases causing ozone depletion. Newer CFC-free devices are now being
replaced with inhalers that use hydrofluoroalkanes (HFAs) as a propellant.
All DPIs are already CFC-free.
Spacer/Holding Chamber Devices
To overcome the administration problem, spacers have been developed
that avoid the need to co-ordinate inhaler actuation and inhalation.22
Spacers/holding chambers are simple tube extensions to the actuator
mouthpiece, one-way valved holding chambers (VHCs), or reversed-flow
devices. The rationale for spacers is that by increasing the distance between
the point of aerosol generation and the patient’s mouth, the oropharyngeal
deposition is reduced, thus increasing lung deposition.23
Current guidelines recommend VHCs as a viable alternative to nebulizers for
delivering large bronchodilator doses to patients with severe acute asthma
or COPD.24 A Cochrane review showed that the relative risk for
hospitalization in children over two years of age and adults with acute
asthma was not significantly different whether they received beta-agonists
through a nebulizer or pMDI with spacer/VHC.25
While spacers have proven clinical benefits, they may not be ideal for all
patients, particularly those with active lifestyles, because they are
cumbersome and may cause embarrassment.
Dry Powder Inhalers
Dry powder inhalers (DPIs) are activated through inhalation by the patient.
The asthma medication comes in a dry powder formulation inside a small
capsule that is placed inside the inhaler. DPIs do not require a propellant, but
1.
Pleis JR, Lethbridge-Çejku M, Summary health statistics for US
adults: National Health Interview Survey, 2006. National Center
for Health Statistics, Vital Health Stat, 2007:10(235).
2. Bloom B, Cohen RA, Summary Health Statistics for US Children,
National Health Interview Survey, 2006. National Center for
Health Statistics, Vital Health Stat, 2007;10(234).
3. Weiss KB, Sullivan SD, The health economics of asthma and
rhinitis: assessing the economic impact, J Allergy Clin Immunol,
2001;107:3–8.
4. Minino AM, Heron MP, Smith BL, Deaths: Preliminary Data for
2004, National Vital Statistics Reports, 2006;54.
5. National Asthma Education and Prevention Program (NAEPP),
Expert panel report 3: guidelines for the diagnosis and
management of asthma, National Heart, Lung, and Blood
Institute, Bethesda (MD), 2007:213–76.
6. Walters EH, Walters J, Gibson P, et al., Inhaled short acting
beta2-agonist use in chronic asthma: regular versus as needed
treatment, Cochrane Database Syst Rev, 2003;1:CD001285.
7. Salpeter SR, Ormiston TM, Salpeter EE, Meta-analysis: respiratory
tolerance to regular beta2-agonist use in patients with asthma,
Ann Intern Med, 2004;140(10):802–13.
8. Qaseem A, Snow V, Shekelle P, et al., Clinical Efficacy Assessment
Subcommittee of the American College of Physicians, Diagnosis
and management of stable chronic obstructive pulmonary
disease: a clinical practice guideline from the American College
of Physicians, Ann Intern Med, 2007;147(9):633–8.
9. Rabe KF, Hurd S, Anzueto A, et al., Global Initiative for Chronic
Obstructive Lung Disease, Global strategy for the diagnosis,
management, and prevention of chronic obstructive pulmonary
disease: GOLD executive summary, Am J Respir Crit Care Med,
2007;176(6):532–55.
10. American Thoracic Society/European Respiratory Society Task
US RESPIRATORY DISEASE
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
do require a relatively rapid rate of inhalation in order to provide the energy
necessary for drug aerosolization.24 This type of device is currently used with
long-acting beta agonists (LABAs) and anticholinergics (tiotropium), or
inhaled corticosteroids (ICS).
Breath-actuated Inhalers
Like DPIs, breath-activated pMDIs overcome the problem of co-ordinating
inhalation and actuation. Inhalation at the mouthpiece activates the
release of the dose.26 As the patient inhales through the mouthpiece of
the device, a triggering mechanism releases the drug. The device has a
pressurized propellant system that is actuated with an inspiratory flow
of 30l/minute.27
Studies have demonstrated that the breath-actuated device can be used
successfully in patients with severe airflow limitations28 and is simple to
use, particularly in elderly treatment-naïve patients.29–31 The most
common reason for unsuccessful use was an inadequate inspiratory
volume to activate the canister due to participants halting their
inspiration early or not beginning their inspiration at functional capacity
or residual volume.29
Summary and Conclusions
SABAs remain the gold standard for treating acute bronchospasm and
for the prevention of EIB. However, the suboptimal use of conventional
pMDIs remains a problem, and can result in inconsistent dosing. A major
limitation associated with pMDIs is patients being unable to co-ordinate
inspiration with pressing the button to release medication. Assessing a
patient’s ability to handle a pMDI, properly prepare and actuate the
pMDI, and co-ordinate actuation, and providing suitable patient training
are essential. ■
Force, Standards for the Diagnosis and Management of Patients
with COPD, Version 1.2, New York: American Thoracic Society,
2004, 2005. Available at: www.thoracic.org/go/copd
Op’t Holt TB, Inhaled beta agonists, Respir Care, 2007;52(7):
820–32.
Carl JC, Myers TR, Kirchner HL, et al., Comparison of racemic
albuterol and levalbuterol for treatment of acute asthma,
J Pediatr, 2003;143(6):731–6.
Skoner DP, Greos LS, Kim KT, et al., Evaluation of the safety and
efficacy of levalbuterol in two to five-year-old patients with
asthma, Pediatr Pulmonol, 2005;40(6):477–86.
Milgrom H, Skoner DP, Bensch G, et al., Levalbuterol Pediatric
Study Group, Low-dose levalbuterol in children with asthma:
safety and efficacy in comparison with placebo and racemic
albuterol, J Allergy Clin Immunol, 2001;108(6):938–45.
Handley DA, Tinkelman D, Noonan M, et al., Dose-response
evaluation of levalbuterol versus racemicalbuterol in patients
with asthma, J Asthma, 2000;37(4):319–27.
Tinkelman DG, Brandon ML, Grieco M, et al., Comparison of
safety and efficacy of inhaled pirbuterol with metaproterenol,
Ann Allergy, 1990;64:202–6.
Epstein SW, Manning CP, Ashley MJ, et al., Survey of the clinical
use of pressurized aerosol inhalers, Can Med Assoc J,
1979;120(7):813–16.
Bailey WC, Richards JM, Brooks CM, et al., A randomized clinical
trial to improve self-management practices of adults with
asthma, Arch Intern Med, 1990;150:1664–8.
Goodman DE, Israel E, Rosenberg M, et al., The influence of age,
diagnosis, and gender on proper use of metered-dose inhalers,
Am J Respir Crit Care Med, 1994;150:1256–61.
Todd MA, Baskett JJ, Richmond DE, Inhaler devices and the
elderly, N Z Med J, 1990;103:43–6.
21. Kamps AW, Brand PL, Roorda RJ, Determinants of correct
inhalation technique in children attending a hospital-based
asthma clinic, Acta Paediatr, 2002;91(2):159–63.
22. Currie GP, Douglas JG, Oxygen and inhalers, BMJ, 2006;333:
34–6.
23. Newman SP, Spacer devices for metered dose inhalers, Clin
Pharmacokinetics, 2004;43(6):349–60.
24. Dolovich MB, Ahrens RC, Hess DR, et al., Device selection and
outcomes of aerosol therapy: evidence-based guidelines, Chest,
2005;127(1):335–71.
25. Cates CJ, Crilly JA, Rowe BH, Holding chambers (spacers) versus
nebulizers for beta-agonist treatment of acute asthma, Cochrane
Database Syst Rev, 2006;(2):CD000052.
26. O’Callaghan C, Wright P, The metered-dose inhaler. In: Bisgaard
H, O’Callaghan C, Smaldone GC (eds), Drug Delivery to the Lung,
New York: Marcel Dekker, 2002;337–70.
27. Marshik PL, Larsen JS, Leach CL, et al., A novel breath actuated
device (Autohaler™) consistently actuates during the early
phase of inspiration, J Aerosol Med, 1995;8:187–95.
28. Fergusson RJ, Lenney J, McHardy GJ, et al., The use of a new
beath-actuated inhaler by patients with severe airflow
obstruction, Eur Respir J, 1991;4(2):172–4.
29. Chapman KR, Love L, Brubaker H, A comparison of
breath-actuated and conventional metered-dose inhaler
inhalation techniques in elderly subjects, Chest,
1993;104(5):1332–7.
30. Diggory P, Bailey R, Vallon A, Effectiveness of inhaled
bronchodilator delivery systems for elderly patients, Age Aging,
1991;20:379–82.
31. Arthur V, Pushkin S, Emery P, Inhaler use in patients with arthritic
hands, Clin Trials Meta-analysis, 1992;28:23–8.
13