Download MtM essentials for asthma management: part 2

CREDIT:
2.0
Continuing Education
EARN CE CREDIT FOR THIS ACTIVITY AT WWW.DRUGTOPICS.COM
AN ONGOING CE PROGRAM OF THE UNIVERSITY OF CONNECTICUT
SCHOOL OF PHARMACY AND DRUG TOPICS
educationaL oBJectiVeS
Goal: The goal of this activity is to review
the stepwise approach to the management
of pediatric and adult asthma and the
pharmacotherapies commonly used in asthma
treatment.
After participating in this activity, the
pharmacist should be able to:
●
●
●
Explain the step-care approach to the
management of asthma
Discuss pharmacologic options for the
management of asthma in adult and
pediatric populations
Discuss how pharmacists can identify and
resolve adherence issues in patients with
asthma
Describe factors that contribute to health
disparities in asthma care and ways to
minimize these factors
The University of Connecticut School of
Pharmacy is accredited by the Accreditation
Council for Pharmacy Education as a provider
of continuing pharmacy education.
Pharmacists are eligible to participate in the
knowledge-based activity, and will receive up to 0.2
CEUs (2 contact hours) for completing the activity,
passing the quiz with a grade of 70% or better, and
completing an online evaluation. Statements of
credit are available via the online system and your
participation will be recorded with CPE Monitor within
72 hours of submission.
ACPE# 0009-9999-15-030-H01-P
Grant funding: This activity is supported by an independent educational grant from Boehringer Ingelheim
Pharmaceuticals, Inc.
Supported by an educational grant from Genentech
Novartis Pharmaceuticals Corporation
Activity Fee: There is no fee for this activity.
Initial release date: May 10, 2015
Expiration date: May 10, 2018
To obtain CPE credit, visit www.drugtopics.com/cpe
and click on the “Take a Quiz” link. This will direct
you to the UConn/Drug Topics website, where you will
click on the Online CE Center. Use your NABP E-Profile
ID and the session code: 15DT30-PYJ23 to access
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For questions concerning the online CPE
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MtM essentials for
asthma management:
part 2
Stefanie Nigro, PharmD, BCACP, BC-ADM
ASSISTANT PROFESSOR, MCPHS uNIVERSITY, BOSTON, MASS.
Diana M. Sobieraj, PharmD, BCPS
ASSISTANT PROFESSOR OF PHARMACY PRACTICE, uNIVERSITY OF CONNECTICuT SCHOOL OF PHARMACY,
STORRS, CONN.
Abstract
After asthma is diagnosed and the severity of asthma is determined, proper
pharmacotherapy must be implemented to improve asthma control, reduce
symptoms, and enhance the patient’s quality of life. Guidelines suggest the use
of a stepwise approach to modify therapy as asthma control changes. The key
maintenance therapy for patients of all ages with asthma is inhaled corticosteroids.
All patients with asthma should also have access to a short-acting beta-agonist
inhaler for quick relief of acute symptoms. Alternative therapies exist, although they
are not generally preferred for the most optimal control. In addition to optimizing
pharmacotherapy, pharmacists should work to promote adherence to medications
and reduce health disparities in asthma management, which will lead to more
widespread success of asthma control.
Faculty: Stefanie nigro, Pharmd, BcacP, Bc-adM and diana M. Sobieraj,
Pharmd, BcPS
Dr. Nigro is an assistant professor of pharmacy practice, MCPHS university, Boston, Mass. Dr. Sobieraj is
an assistant professor of pharmacy practice, university of Connecticut School of Pharmacy, Storrs, Conn.
Faculty Disclosure: Dr. Nigro and Dr. Sobieraj have no actual or potential conflict of interest associated
with this article.
Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion
of unlabeled/unapproved use of drugs in the united States and will be noted if it occurs. The content and
views presented in this educational program are those of the faculty and do not necessarily represent
those of Drug Topics or university of Connecticut School of Pharmacy. Please refer to the official
information for each product for discussion of approved indications, contraindications, and warnings.
44
Drug topics
May 2015
DrugTopics .c om
IMAGE: GETTY IMAGES / PHOTOALTO/MICHELE CONSTANTINI
●
continuing education
cpE sEriEs: MtM For tHE pAtiENt WitH rEspirAtorY
DisEAsE
Welcome to the CPE series, Medication
Therapy Management for the Patient
with Respiratory Disease, which was
designed for pharmacists who take
care of patients with respiratory disease.
Beginning in April 2015 and continuing
through December 2015, pharmacists
can earn up to 18 hours of CPE credit
with 9 monthly knowledge-based activities from the university of Connecticut
School of Pharmacy and Drug Topics.
This series kicked off last month
with MTM essentials for asthma management, covering the pathophysiol-
introduction
After asthma has been diagnosed and the
severity of asthma has been assessed,
proper pharmacotherapy must be implemented to improve asthma control, reduce
symptoms, and enhance the patient’s
quality of life. The Expert Panel Report
3 from the National Asthma Education
and Prevention Program (NAEPP EPR-3)
recommends a stepwise approach to the
implementation and adjustment of pharmacotherapy in asthma management.1 In
this article, the stepwise approach will be
reviewed, as will the suggested pharmacotherapy options. The importance of adherence to medication regimens and awareness of health disparities in asthma will
also be discussed. For a complete review
of the pathophysiology and clinical presentation of asthma in addition to the assessment of asthma severity and control and
nonpharmacologic management strategies, please consult the article “MTM Essentials for Asthma Management: Part 1”
in the April 2015 issue of Drug Topics.2
Managing asthma:
A step-care approach
Initial pharmacotherapy selection is based
on disease severity; modifications to therapy
are based on disease control. Timely and
ongoing assessment of control is important
because current asthma control predicts
future instability in asthma control and exacerbations.3 Therefore, the ultimate goal
of asthma care is the achievement and
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ogy of asthma, clinical presentations
of asthma, assessment methods, and
nonpharmacologic management options. This month the second part of
MTM essentials for asthma management includes the step-care approach of
management, pharmacologic options for
adults and children, adherence issues,
and ways to minimize health disparities
in asthma care.
In June and July, the focus shifts to
MTM essentials for chronic obstructive
pulmonary disease (COPD) management. The August CE activity is a primer
maintenance of asthma control. This is accomplished by reducing both impairment and
risk. Impairment is minimized by preventing
chronic and troublesome symptoms, maintaining (near) normal pulmonary function,
maintaining normal activity levels, using
rescue medication no more than two days
per week, and meeting the patient’s and
family’s expectations and satisfaction with
asthma care.1 Similarly, risk can be reduced
by providing optimal pharmacotherapy with
minimal adverse effects, preventing exacerbations that would require hospitalization,
and preventing progressive loss of lung function.1 A patient’s level of asthma control (ie,
well controlled, not well controlled, or poorly
controlled) will help to guide adjustments to
pharmacotherapy, so periodic assessment
of disease control at one- to six-month intervals is critical.1 For a review of severity and
control assessment, see “MTM essentials
for asthma management: Part 1” in the April
2015 issue of Drug Topics.2
National guidelines endorse a stepwise
approach to the management of asthma
(Figures 1-3). After asthma is diagnosed
and the severity is assessed, the stepwise approach is used to determine which
step of therapy should be initiated to correspond with the current level of asthma
severity. The guidelines recommend starting with step 1, step 2, or step 3 in patients
with intermittent asthma, mild persistent
asthma, or moderate persistent asthma,
respectively, regardless of patient age.
Recommendations for treatment selection
on inhalers and nebulizers. In September, pharmacists have the opportunity to
learn about allergic rhinitis management.
In October, the CE activity covers MTM
essentials for cold, flu, and sinusitis
management. The November CE activity includes drug-induced pulmonary disease recognition and management and
idiopathic pulmonary fibrosis. The series
concludes in December with a focus on
MTM essentials for cough management.
The series also offers applicationbased and practice-based activities in
2016.
include both preferred and alternative therapies. Preferred medications refer to those
that have consistent evidence from highquality studies to support improvements
in asthma control versus other therapies.1
Alternative therapies are usually reserved
for those patients who have a contraindication to or cannot tolerate a preferred agent.
The evidence supporting use of alternative
therapies for asthma control is less robust.
In patients aged five to 11 years, the medium-dose inhaled corticosteroid (ICS) option within step 3 is recommended over the
other suggested preferred therapies within
that step. The initial treatment of severe
persistent asthma corresponds with step 3
in patients aged four years and younger and
corresponds with step 3 or 4 in patients
aged five to 11 years. In patients aged
12 years and older with severe persistent
asthma, the guidelines suggest initiating
treatment at step 4 or 5. For any patients
beginning therapy for moderate or severe
persistent asthma, clinicians should consider the addition of a short burst of oral
corticosteroid therapy to help obtain prompt
control of asthma symptoms.
For inadequately controlled asthma, a
step-up approach is recommended to gain
control. Conversely, a step-down approach
is encouraged for patients with asthma that
has been controlled for a sufficient period of
time. For cases classified as well controlled,
maintenance of the current treatment is
advised, with routine follow-up occurring at
one to six months. For cases that are not
May 2015
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45
Continuing Education
MtM eSSentiaLS FoR aStHMa ManageMent: PaRt 2
FIguRE 1
StepwiSe approach to managing aSthma in children aged four yearS and younger
Persistent Asthma: Daily Medication
Intermittent
Asthma
Consult with asthma specialist if step 3 care or higher is required.
Consider consultation at step 2.
Step 6
Step 5
Step 4
Step 3
Preferred:
Medium-dose
ICS
Step 2
Step 1
Preferred:
SABA PRN
Preferred:
Low-dose ICS
Preferred:
Medium-dose
ICS + either
LABA or
Montelukast
Preferred:
Preferred:
High-dose ICS +
either
LABA or
Montelukast
High-dose ICS +
either
LABA or
Montelukast
Oral systemic
corticosteroids
Alternative:
Cromolyn or
Montelukast
Step up if
needed
(first, check
adherence,
inhaler
technique, and
environmental
control)
Assess
control
Step down if
possible
Patient Education and Environmental Control at Each Step
(and asthma is
well controlled
at least
3 months)
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms.
• With viral respiratory infection: SABA q 4-6 hours up to 24 hours (longer with physician consult). Consider short course of oral
systemic corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations.
• Caution: Frequent use of SABA may indicate the need to step up treatment. See text for recommendations on initiating daily
long-term-control therapy.
Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; PRN, as needed; SABA, short-acting beta-agonist.
Notes available in the online version.
Reprinted with permission from the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services (Ref 1).
well controlled, the clinician should ensure
that the patient has had good medication
adherence, has used appropriate inhaler
technique, and has maintained proper control of environmental triggers. In addition, if
the patient is currently using an alternative
therapy within the proper step, attempts
should be made to change to the preferred
therapy when possible. If the asthma is still
not well controlled, pharmacotherapy should
be adjusted by stepping up one step, with
re-evaluation in two to six weeks. For very
poorly controlled asthma, therapy should be
stepped up by one or two steps. Treatment
with a short course of oral corticosteroids
can also be considered for patients exhibiting
severe symptoms. In these cases, follow-up
is advised within two weeks. For cases that
are not well controlled or are very poorly controlled, if no benefit is observed by four to six
weeks after the medication change, further
adjustment of therapy may be needed. For
46
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May 2015
patients experiencing medication intolerance,
alternative therapies should be considered.
Once the patient has maintained asthma
control for at least 3 months, a step down of
the therapy should be considered.1 A 25% to
50% ICS dose reduction every 3 months can
be trialed as part of the step-down approach.
To illustrate the use of the step-up approach, imagine you are a pharmacist conducting MTM for a 46-year-old woman with
asthma. In speaking with your patient, you
learn that she was recently diagnosed with
mild persistent asthma. Two months ago,
treatment with low-dose fluticasone was
initiated (step 2), and your patient is also
continuing to use the short-acting beta-2
agonist (SABA) rescue inhaler she was
prescribed immediately after her diagnosis (step 1) (Figure 3). Today, she reports
that she has had shortness of breath
three times in the past week, causing nocturnal awakenings. Because of this, she
has been using her SABA more regularly
(estimated use, three times per week).
She scores a 17 on the asthma control
test (ACT). [Note: A score of 19 or less on
the ACT indicates that asthma may not be
as well controlled as it should be]. When
asked, she denies any missed doses and
is able to demonstrate proper inhaler technique. No other changes to her medication and/or health are noted, and she is
currently on the preferred therapy within
step 2 for a patient of her age. Based on
her reported symptoms, the patient is
showing evidence of impairment without
risk. Her asthma is classified as not wellcontrolled, necessitating an adjustment in
her therapy. Because her asthma is “not
well-controlled” and not “very poorly controlled”, a one-step adjustment to step 3
is recommended. She should be re-evaluated within two to six weeks to reassess
her asthma control.
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continuing education
Figure 2
Stepwise approach to managing asthma in children aged five to eleven years
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.
Step 6
Step 5
Step 4
Step 3
Step 2
Step 1
Preferred:
SABA PRN
Preferred:
Low-dose ICS
Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline
Preferred:
EITHER:
Low-dose ICS +
either LABA,
LTRA, or
Theophylline
OR
Medium-dose
ICS
Preferred:
Medium-dose
ICS + LABA
Alternative:
Medium-dose
ICS + either
LTRA or
Theophylline
Step up if
needed
Preferred:
Preferred:
High-dose ICS +
LABA
Alternative:
High-dose ICS +
either LTRA or
Theophylline
High-dose ICS +
LABA + oral
systemic
corticosteroid
Alternative:
High-dose ICS +
either LTRA or
Theophylline +
oral systemic
corticosteroid
(first, check
adherence,
inhaler
technique,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)
Each step: Patient education, environmental control, and management of comorbidities
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma
(see notes).
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute
intervals as needed. Short course of oral systemic corticosteroids may be needed.
• Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates
inadequate control and the need to step up treatment.
Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LTRA, leukotriene receptor antagonist; SABA, short-acting beta-agonist.
Notes available in the online version.
Reprinted with permission from the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services (Ref 1).
Assessment of control can sometimes
be challenging because of differences in patients’ and providers’ perceptions of control.
A 2006 telephonic survey was designed to
assess both asthma control among adult patients and knowledge and practices among
providers actively involved in asthma management.4 For the purposes of this study, control
was defined based on symptoms outlined in
consensus guidelines. Of the 893 patients
surveyed, 97% perceived their asthma to be
well controlled, when in fact only 47% of cases were actually well controlled according to
guideline criteria.4 Moreover, of the 463 providers studied, only 6% reported using clinical
practice guidelines routinely, with an additional 33% reporting the use of these guidelines
“most of the time.” These findings suggest a
need to improve education regarding asthma
control among patients with asthma and the
providers who care for them.
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Treatment approaches
for managing asthma in
children and adults
Treatment approaches for the management
of asthma differ slightly among children and
adults despite similar symptomatology. This
is due in part to subtle and unique differences in the pathogenesis of asthma in children and adults. Asthma can develop at any
phase of life, but the prevalence of asthma
onset is highest among children of preschool
age; approximately 50% to 80% of children
with asthma will develop symptoms before
age 5.1 Asthma is the leading cause of hospitalization among children.1 Children with
asthma have more atopic disease with higher levels of serum IgE, whereas adult-onset
asthma is commonly caused by genetic and
environmental factors.5 Both patient populations, however, often present with comorbid
allergic rhinitis.5 Classic asthma-related symp-
toms can be episodic in children yet persistent in adults. Additionally, asthma is often
underdiagnosed in children, a problem that
is further complicated by a lack of reliable
objective measurements of lung function.1
Treatment in children. The goal of asthma management in children is to maintain
long-term control using the fewest medications possible at the lowest effective dose
to minimize adverse drug events such as
growth stunting.1 Daily long-term controller
therapy can be initiated in infants and young
children aged four years and younger who:
■ Have experienced four or more wheezing episodes in the past year (lasting more
than one day) that affected sleep AND have
an increased risk for the development of persistent asthma; OR
■ Have required consistent symptomatic
treatment more than two days per week for
more than four weeks; OR
May 2015
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47
Continuing Education
MtM eSSentiaLS FoR aStHMa ManageMent: PaRt 2
FIguRE 3
StepwiSe approach to managing aSthma in patientS aged 12 yearS and older
Persistent Asthma: Daily Medication
Intermittent
Asthma
Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.
Step 6
Step 5
Step 4
Step 3
Step 2
Step 1
Preferred:
SABA PRN
Preferred:
Low-dose ICS
Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline
Preferred:
Low-dose
ICS + LABA,
OR
Medium-dose ICS
Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton
Preferred:
Medium-dose
ICS + LABA
Alternative:
Medium-dose
ICS + either
LTRA,
Theophylline, or
Zileuton
Preferred:
Preferred:
High-dose ICS +
LABA
High-dose ICS +
LABA + oral
corticosteroid
AND
AND
Consider
Omalizumab for
patients who
have allergies
Consider
Omalizumab for
patients who
have
allergies
Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)
Each step: Patient education, environmental control, and management of comorbidities.
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute
intervals as needed. Short course of oral systemic corticosteroids may be needed.
• Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to
step up treatment.
Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LTRA, leukotriene receptor antagonist; PRN, as needed; SABA, short-acting beta-agonist.
Notes available in the online version.
Reprinted with permission from the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services (Ref 1).
■ Have experienced a second asthma
exacerbation requiring systemic corticosteroids within the previous six months; OR
■ Have had periods of previously documented risk (eg, seasonal asthma).
For children aged five to 11 years, longterm daily controller therapy is recommended for those with documented persistent
asthma. Low-dose ICS remains the preferred
initial treatment option for children of all age
groups with persistent asthma (step 2).1 It is
believed that the benefits of improved asthma control outweigh the potential (but small)
risk of delayed growth seen with ICS.1 Clinical studies for the management of asthma
in children aged four years and younger are
limited; therefore, recommendations regarding medications other than low-dose ICS are
based on expert opinion only. Similarly, many
treatment recommendations for children
aged five to 11 years are based on extrapolation from comparator trials in older children
48
Drug topics
May 2015
and adults. Full step-up recommendations
for children are depicted in Figures 1 and 2.1
Referral to an asthma specialist should be
considered for children aged four years and
younger who require step 3 or higher, as well
as for patients aged five to 11 years who
require step 4 or higher. To improve medication delivery, children are encouraged to use
spacers and facemasks with inhaled therapy. Further information regarding inhalers
and devices in asthma management will be
presented in the August issue of this series.
Treatment in adults. As with asthma
management in children, the goal of asthma treatment in patients aged 12 years and
older is to achieve long-term control using
the least amount of medications possible.
Pharmacotherapy recommendations and
preferences are shown in Figure 3.1 Specific
therapy needs to be tailored for individual
patients. A long-term, daily controller medication with anti-inflammatory properties is the
initial recommendation for the treatment of
persistent asthma (step 2); ICS is preferred.
Referral to an asthma specialist should be
considered for patients requiring step 4 care
or higher or when the use of immunotherapy
is being considered.1 The guiding principles
of stepping up or stepping down therapy apply across all age groups; however, several
unique treatment issues must be considered when designing a care plan for older
adults. Changes in physical dexterity and
cognition can make use of an inhaler challenging, so more frequent assessment of
proper technique is advised. Additionally,
certain asthma medications may have an
increased risk of side effects and/or drug
interactions in this patient population, warranting adjustments to therapy. For example,
theophylline is not eliminated as quickly in
older adults, increasing the potential for side
effects such as nausea, vomiting, insomnia,
and/or tremor. To avoid toxicity, lower doses
DrugTopics .c om
continuing education
should be used and dose reductions may be
necessary throughout treatment. Similarly,
beta-agonists can precipitate cardiac effects such as tachycardia and tremor, and
oral corticosteroids can cause changes in
mental status or glucose metabolism. Pharmacists can help to identify, prevent, and
resolve such medication-related problems.
All patients with asthma, regardless of
age, should have a written asthma action
plan as part of the management process.1
This allows patients to take an active role
in self-management of asthma. The written
plan should highlight information regarding
the use of daily medications along with
recognition and management of worsening asthma.1 Patients should be taught
how to self-adjust their medications based
on the presence of acute and/or alarming symptoms. Both peak-flow-based and
symptom-based asthma action plans can
be effective.1 The National Heart, Lung,
and Blood Institute offers an asthma action
plan template (available in both English and
Spanish), which is available at http://www.
nhlbi.nih.gov/health/resources/lung/asthmaaction-plan.6 Asthma action plans should be
re-evaluated and revised (if necessary) at
each follow-up encounter.
Color-based “zones” are used in asthma
action plans to categorize symptoms and offer treatment recommendations. A patient
in the green zone is doing well and can
perform usual activities without symptoms
of asthma. Management for these patients
includes the use of controller medications
and SABAs as needed. For patients with
exercise-induced bronchoconstriction (EIB),
a SABA can be used five to 15 minutes
before physical activity. Patients are in the
yellow zone if they display symptoms of
worsening asthma such as cough, wheeze,
shortness of breath, nocturnal awakenings,
or impairment in usual activities. These patients should be instructed to continue their
green-zone medications and to use two to
four puffs of a quick-acting SABA every 20
minutes for up to one hour during periods
pause&ponder
in your daily
practice, how can
you help patients
with asthma to
achieve control of
the condition?
DrugTopics .c om
of worsening symptoms. Alternatively, one
SABA treatment via nebulizer can be used in
lieu of an inhaler. If the symptoms subside,
patients should continue using their greenzone medications. If the symptoms do not
improve and/or worsen after 1 hour of treatment, additional use of a SABA is recommended along with adding an oral steroid,
usually for three to 10 days. Patients should
call their healthcare professional shortly after
taking the steroid. Patients in the red zone
may exhibit severe symptoms including
marked wheezing, shortness of breath, and
an inability to speak or perform usual activities; these cases are medical emergencies.
These patients should begin treatment immediately and call their healthcare provider.
Treatment involves the use of rescue medications and an oral corticosteroid burst. If
the treatment response is poor, the patient
is advised to repeat the SABA treatment immediately and call 911.6
pharmacologic
management of asthma
The NAEP EPR-3 suggests first-line preferred therapies for asthma control; these
therapies should be used whenever possible. Within certain steps, there may be
a suggested alternative, but clinicians
should attempt to maintain the use of
preferred therapies whenever possible.1
Beta-agonists. Inhaled SABAs are the
most effective therapy for reversing airway
bronchoconstriction and are the drug of
choice for rapid symptom relief in asthma,
asthma exacerbations, and prevention of
EIB.1 All patients with asthma should be
prescribed an inhaled SABA to be used as
needed for control of symptoms. As the drug
of choice for the prevention of EIB, SABAs
should be taken five minutes before the
physical activity that causes asthma symptoms. Through the stimulation of beta2-adrenergic receptors on the pulmonary smooth
muscle, SABAs lead to bronchodilation in
less than five minutes, with a duration of
action of four to six hours.
Albuterol is the most common inhaled
SABA used in asthma management and
is available as a solution for nebulization
and as a metered dose inhaler (MDI). The
R-enantiomer of albuterol, levalbuterol, is
also available as a nebulizer solution and
MDI; this formulation may be associated
with fewer side effects (including tachycar-
dia), although the data are inconclusive.7,8
Patients who may benefit from levalbuterol
over albuterol include those with asthma and
concurrent cardiovascular disease, especially
conditions that could potentially worsen with
tachycardia such as decompensated heart
failure or poorly controlled arrhythmias.8
Both albuterol and levalbuterol MDIs,
when used as rescue inhalers, are typically dosed at two puffs every four to six
hours as needed, although levalbuterol is
not indicated for children aged younger than
five years. The dose of SABA used in acute
exacerbations is higher and can reach four
to eight puffs every 20 minutes for four
hours in patients aged 12 years and older.1
Higher doses of SABA may be needed to
relieve acute asthma symptoms if patients
are also taking a nonselective beta-blocker
(NSBB), although NSBBs should generally
be avoided in asthmatics.1
SABA side effects are dependent on
dose and route of administration, with few
systemic side effects when the usual doses
are delivered through the inhaled route. The
most common side effects of inhaled SABAs
include skeletal muscle tremor, nervousness,
cough, rhinitis, and dry mouth. Patients with
cardiovascular disease, especially those of
advanced age, may have cardiovascular adverse events with inhaled therapy.1
The long-acting beta-agonists (LABAs)
salmeterol and formoterol are adjunctive
maintenance therapies used for asthma
management in patients aged five years
and older; there is a lack of clinical trial data
regarding the use of LABAs in children aged
younger than five years.1 LABAs improve
lung function, reduce SABA requirements,
and increase the number of symptom-free
days. However, because of a risk of asthmarelated deaths with these agents, LABAs are
not indicated as monotherapy without an ICS
in patients with asthma and carry a blackbox warning for this reason.9,10 This warning
is based on the results of the Salmeterol
Multicenter Asthma Research Trial (SMART),
which was terminated prematurely because
of an interim analysis that found increased
respiratory and asthma-related deaths in patients randomized to salmeterol versus those
randomized to placebo. African American patients, especially those who were not taking
ICSs at enrollment, were at the highest risk.
Several hypotheses for this increased risk
have been proposed, including direct carMay 2015
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Continuing Education
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diotoxic effects of LABAs, genetic polymorphisms increasing the risk of adverse effects
from LABAs, and the potential masking effect of LABAs on inflammation.9 As such, the
Food and Drug Administration suggests that
LABA use without an ICS is contraindicated
in asthma patients. Once asthma control
is achieved with the addition of a LABA to
ICS, stepping down therapy to remove the
LABA should be considered when possible.10
Clinicians should consider prescribing inhalers with combinations of a LABA and an ICS
to avoid a scenario in which a patient may
self-discontinue an ICS but continue taking
a LABA. Examples of such inhalers include
fluticasone and salmeterol Diskus or MDI,
budesonide and formoterol MDI, and mometasone and formoterol MDI.
The onset of action of salmeterol is
within 30 minutes, and the onset of action of formoterol is similar to that of albuterol. Despite their relatively quick onset
of action, LABAs are not indicated for acute
symptom relief or for exacerbations.1 Both
LABAs have a duration of action lasting 12
hours and are dosed twice daily. Because
LABAs are more selective and lipophilic than
albuterol, exposure outside of the lungs is
reduced and systemic side effects are rare.
Corticosteroids. ICSs are the mainstay
of therapy in the management of persistent
asthma and are always preferred over other
alternative therapies, for all age categories,
because of the central role inflammation
plays in the pathophysiology of asthma.1
ICS improve symptom control and quality
of life, improve measures of lung function,
reduce airway hyperresponsiveness, and
reduce the need for systemic steroids,
emergency room care, hospitalizations, and
asthma-related deaths.1 Currently, there are
six ICSs marketed for asthma treatment:
budesonide, beclomethasone, flunisolide,
fluticasone, ciclesonide, and mometasone.
These corticosteroids are equally efficacious
when dosed at equipotent doses; ICSs are
not equivalent on a puff-per-puff basis.
Figure 18 in the NAEPP EPR-3 guideline
specifies the doses for each marketed ICS
that are considered “low,” “medium,” and
“high” for each age category, corresponding
to the stepwise approach for asthma management.1 Ciclesonide does not appear in
Figure 18 of the NAEPP EPR-3 because its
approval proceeded the latest guidelines. As
it is approved for use in patients 12 years
50
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May 2015
and older, based on clinical studies the
suggested low, medium and high dose is
160-320 mcg, >320-640 mcg, >640 mcg,
respectively.11 Pharmacists are encouraged
to refer to the guidelines whenever checking
ICS dosages to ensure that the prescribed
dose is meeting the desired step and that
when a change in dose is made, the change
is sufficient to move along the stepwise approach. For example, in a patient aged five
to 11 years, a low dose of fluticasone MDI
is considered to be 88 to 176 mcg per day.
Increasing to a medium dose would require
achieving a total daily dose of greater than
176 to 352 mcg, and increasing to a high
dose would require achieving a daily dose
greater than 352 mcg. For a child currently
at a low dose of fluticasone (using a 44-mcg
inhaler and taking one puff twice daily [88
mcg per day]) who required a step up to
a medium dose, simply increasing the regimen to two puffs twice daily (176 mcg per
day) would increase the total daily dose but
not to the amount required to be considered
a medium dose. Two ICSs—budesonide
and fluticasone—have doses recommended by the guidelines for children as young as
one year of age, and budesonide is available
as a nebulizer solution.1
Patients should be advised to allow at
least two weeks for the onset of ICSs to
be noted, with upwards of four to six weeks
of treatment required before full effects are
seen. ICSs have a flat dose-response curve;
therefore, less benefit is achieved when increasing the dose compared to the benefit
seen when first initiating treatment. Common side effects of ICSs include cough,
dysphonia, and oral candidiasis. The use of
a valved holding chamber can reduce the
deposition of ICS particles into the oropharynx and minimize these side effects.1 Systemic side effects are rare when low- and
medium-dose ICSs are used, although high
doses of ICSs may lead to systemic adverse
events such as adrenal suppression, osteoporosis, skin thinning, and easy bruising.1 A
decline in growth velocity has been noted in
children using even low doses of ICSs, but
the guidelines state that the clinical implications of such findings have not been established.1 More recent studies support the
slower growth velocity observed in children
using ICS. However, the greatest impact occurs within the first year of ICS use, is not
cumulative, and expert opinion believes this
risk to be small relative to the large benefit
ICSs are known to have on overall asthma
outcomes.12 Fluticasone, budesonide, and
mometasone are substrates of CYP3A4, so
when these agents are used at high doses
concurrently with a strong CYP3A4 inhibitor, systemic exposure may increase, and
cases of Cushing syndrome and secondary
adrenal insufficiency have been reported.1
Systemic corticosteroids, including
prednisone, methylprednisolone, and prednisolone, are primarily used during asthma
exacerbations and for acute symptom control when a patient is unresponsive to SABAs. When short-term control is needed,
the NAEP EPR-3 suggest a dose of 1 to
2 mg/kg/day with a maximum of 60 mg/
day for three to ten days in patients aged
younger than 12 years and a dose of 40
to 60 mg/day as a single dose or two divided doses for three to ten days in older
patients.1 Asthmatics with the most severe
persistent category of disease may require
daily steroid therapy for long-term control;
in these cases, the daily dose should
be the lowest dose possible to maintain
control but also to minimize the long-term
consequences of systemic steroid exposure. Systemic exposure in the short
term can lead to glucose dysregulation,
increased appetite, fluid retention, mood
changes, and peptic ulcer disease. Longterm consequences include adrenal axis
suppression, growth suppression, dermal
thinning, hypertension, Cushing syndrome,
cataracts, muscle wasting, and, rarely, impaired immune function.1
Leukotriene receptor modifiers. Leukotriene receptor modifiers are orally dosed
therapies represented by two classes: the
5-lipoxengenase inhibitor zileuton and the
direct leukotriene antagonists montelukast
and zafirlukast. Leukotriene receptor modifiers are significantly less effective than ICSs
and for this reason are used as an alternative maintenance therapy (not preferred) or
alternative adjunctive therapy in addition to
ICS in place of LABA in asthma care.1 Montelukast is indicated for the treatment of
asthma in patients aged as young as one
year and has several advantages over other
drugs in this class. Montelukast is available
in multiple dosage forms; chewable tablets
for children as young as 2 years, granules for
children as young as 12 months, and filmcoated tablets for patients 15 years of age
DrugTopics .c om
continuing education
and older. Montelukast is dosed once daily
at bedtime without regard to food, is free
from clinically significant drug interactions,
and also has approval for use in EIB and
seasonal allergic rhinitis. Zileuton and zafirlukast require monitoring of liver function tests
because of a risk of hepatotoxicity; additionally, both of these medications are dosed
twice daily, zafirlukast with food. Zafirlukast
is also an inhibitor of CYP2C9. The guidelines state that zileuton is a less desirable
choice in this class because of a lack of efficacy data and the aforementioned disadvantages. 1 Pharmacists should be aware of
the risk for neuropsychiatric events with this
class of medications and should counsel
patients who experience adverse effects to
contact their prescribers.13, 14
Mast cell stabilizers. Cromolyn is a mast
cell stabilizer available as a nebulizer solution
and as an MDI that can be used as an alternative maintenance therapy in cases of mild
persistent asthma. This agent can be used
in children aged as young as two years and
is generally considered benign, aside from a
risk of cough and mouth irritation, and free
from drug interactions. The onset of action is
at least two weeks; this delayed onset of action and a dosing regimen of four times per
day are less convenient than other options
and have led to the infrequent clinical use of
this medication. Cromolyn is also indicated,
although not preferred, for the prevention of
EIB and can be used prophylactically upon
unavoidable exposure to known allergens.1
Anticholinergics. Ipratropium, available
as an MDI and as a nebulizer solution, is
indicated as an alternative rescue medication for patients with an intolerance to
SABAs. Ipratropium causes bronchodilation
through antagonism of muscarinic receptors in the bronchial smooth muscle. The
onset of action is slower than albuterol (30
minutes), although the duration of action
is longer (four to eight hours). In cases of
moderate to severe asthma exacerbations
requiring emergency room care, the addition
of ipratropium to albuterol decreases hos-
pause&ponder
Within your
current practice
setting, how can
you work to reduce
health disparities
in asthma?
DrugTopics .c om
pitalization rates.1 The most common side
effect of ipratropium is dry mouth, but patients with narrow-angle glaucoma, prostatic
hyperplasia, or bladder neck obstruction are
at risk of symptom worsening. Additionally,
in patients with chronic obstructive pulmonary disease, ipratropium may increase cardiovascular risk.15
Methylxanthines. Theophylline is a mild
to moderate bronchodilator that may have
mild anti-inflammatory properties.1 Sustained-release theophylline, an oral dosage
form, is recommended by the guidelines
as an alternative treatment in patients 5
years of age and older with mild persistent asthma (step 2) or as an alternative
adjunctive therapy in addition to ICS (steps
3 and higher), although this medication is
not preferred.1 The overall adverse effects
profile, narrow therapeutic window, variety
of potential drug interactions via CYP isoenzymes, and need for serum monitoring with
this medication have led to the infrequent
use of theophylline in contemporary asthma
management. Theophylline’s half-life is also
variable depending on various patient characteristics such as age, liver function, and
smoking status, making proper dosing more
complex. The guidelines suggest that serum
theophylline concentrations (target of 5 to
15 mcg/mL) should be measured at least
three to five days after therapy is initiated
and should also be obtained in the middle
of the dosing interval. If patients experience signs of theophylline toxicity (severe
headache, tachycardia, nausea, and vomiting), the serum concentration should be
assessed immediately.1
Immunomodulators. Omalizumab is an
anti-IgE monoclonal antibody that prevents
the binding of IgE to receptors found on
mast cells, dendritic cells, and basophils
and subsequently interferes with the allergic
response cascade that ultimately leads to
asthma symptoms. Omalizumab is also implicated in the down-regulation of IgE receptors.16 Omalizumab is indicated for patients
aged 12 years and older with moderate to
severe persistent asthma inadequately controlled on corticosteroids and with a positive
skin test or in vitro reaction to a perennial
aeroallergen.17 The NAEPP EPR-3 guidelines
suggest the use of omalizumab as a maintenance therapy in steps 5 and 6 for patients
aged 12 years and older. Omalizumab is a
subcutaneous injection that is dosed at 150
to 375 mcg every two to four weeks according to patient weight and pretreatment IgE
levels.18 The most common adverse reactions to this medication include arthralgia,
general pain, leg pain, fatigue, dizziness,
fracture, arm pain, pruritus, dermatitis, and
earache. There is a 0.2% risk of anaphylaxis
associated with this drug that can occur after
the first dose or well into therapy, and therefore omalizumab should be administered in
an environment that is able to handle such
reactions safely. Patients should be observed
for a reasonable period of time after injection,
as cases of anaphylaxis have been seen as
late as two hours after the dose.17
promoting adherence to
asthma medications
Achieving and maintaining asthma control remain suboptimal despite advances
in pharmacotherapy and inhaled delivery
systems. One barrier is poor medication adherence, most notably to controller medications.18 Many patients may
choose not to take their asthma medication because of their perception that
it is not necessary and/or because of
a fear of unwanted side effects.18 Other
factors influencing medication adherence
include disease severity, previous experiences with medication, health beliefs,
understanding of the disease, and complexity of the regimen.19, 20 Nonadherence
to therapy is widespread; estimated adherence rates range from 30% to 70%,21
with most studies showing rates of less
than 50%.22 Nonadherence has serious
implications, including airway obstruction, impaired quality of life, and greater
healthcare utilization leading to increased
healthcare spending.1,23 Because of this,
current practice guidelines state that efforts should be made to assess medication adherence at each point of patient
contact.1 A multidisciplinary, team-based
approach to care is recommended to address medication adherence.19 Pharmacists are highly accessible and adequately
trained to assist with asthma care, and
previous pharmacist-led initiatives regarding medication management have led to
improvements in patients’ ACT scores,
asthma-related quality of life, inhaler
technique, and medication adherence.24-26
Nonadherence to asthma medication
varies and may present as a failure to fill
May 2015
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51
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MtM eSSentiaLS FoR aStHMa ManageMent: PaRt 2
TABLE 1
interventionS to improve medication adherence
Cause of nonadherence
Suggested interventions
Forgetfulness
■
Encourage the use of memory aids, reminders, cues, and feedback
■ Offer pharmacy refill programs
Complexity of medication regimen
■
■
Cost of medication regimen
Simplify the medication regimen (eg, combination therapy)
Tailor the regimen to the patient’s needs and/or situation
Use generic medications
Use prescription assistance programs
■ Use drug discount coupons
■ Simplify the medication regimen
■
■
Inappropriate technique
Provide patient education
Frequently assess inhaler technique
■ Use a spacer
■
■
Use a shared decision process
Monitor adherence
■ Implement self-management programs with educational and
behavioral components
■ Offer multidisciplinary care with a common message
Other
■
■
Source: Ref 20, 27
a prescription, overuse of rescue medications, underuse of controller medications,
erratic use of medication, and/or premature discontinuation of therapy.19 Nonadherence is often further delineated as intentional or unintentional. unintentional, or
nondeliberate, adherence refers to failure
to adhere to the treatment plan because
of factors that are often beyond the patient’s control. These factors may include
forgetfulness, poor inhaler technique, poor
understanding of provider instructions,
and inability to obtain the medication
(because of either cost or availability).18
Intentional, or deliberate, nonadherence
occurs when the patient makes a conscious decision not to take a medication
or to alter the way in which a medication
is taken despite receiving medical advice
to the contrary. Being able to differentiate
between these types of nonadherence is
essential to best determine which interventional strategy is needed. Motivational
interviewing is encouraged to address intentional nonadherence. For a full review
of motivational interviewing techniques,
please refer to the article “Motivational
interviewing techniques for chronic disease management” in the October 2014
issue of Drug Topics.27 unintentional nonadherence requires targeted interventions
based on patient-specific factors. Table 1
offers practical solutions for improving asthma medication adherence.20,28
Regardless of the strategy employed,
pharmacists should focus on the positive
52
Drug topics
May 2015
benefits of adherence rather than the negative consequences of nonadherence.26
Pharmacists can also assist with preventing nonadherence by determining
which patients are at high risk for nonadherence. using software applications,
pharmacists can scan dispensing and refill
histories to generate a list of patients who
have been overfilling rescue inhalers or underfilling controller medications.29 This can
help to identify gaps in care and lead to
care coordination with other healthcare professionals. Other methods to detect poor
adherence include frequent assessment of
inhaler technique and routine counseling
about the medication regimen.
Health disparities in
asthma
Asthma disproportionately affects racial and
ethnic minorities and low socioeconomic
populations in the united States. The prevalence of asthma is 25% higher in children of
American Indian or native Alaskan descent,
60% higher in African American children,
and 140% higher in Puerto Rican children
compared with asthma prevalence in white
children.30 In these subgroups, quality of
and access to care is often lower and the
exposure to environmental triggers is higher
than in the rest of the population.30 Mortality
related to asthma is eight-fold higher in nonHispanic black children compared to their
white counterparts.31
The first step in addressing health
disparities in asthma care is to recog-
nize their existence. The guideline Implementation Panel for the NAEP EPR-3 has
made several recommendations as to
how health disparities in asthma can be
reduced.31 Pharmacists are well trained
and positioned to implement many of
these recommendations. Patient education to increase awareness of asthma and
to improve asthma control, especially in
low economic and racial/ethnic minority
populations, is a central intervention to reduce health disparities in asthma. Patient
education material should be available in
the appropriate languages and should be
sensitive to cultural practices. Clinicians
are encouraged to undergo cultural competency training and to provide culturally
and linguistically appropriate care through
effective communication. Translator services should be available when needed to
facilitate communication. Home visits and
educational seminars open to the community can enhance self-management and
awareness of asthma, and payors should
reimburse clinicians to facilitate the provision of such services. Improvement in the
coordination of care across providers and
settings, such as the primary care provider, pulmonologist, and a child’s school, is
encouraged. Additional recommendations
include provision of home inspections and
assistance to low-income or racial/ethnic
minority households to minimize exposure
to environmental triggers and to strategically place schools and residences away
from major sources of air pollution. Last,
quality improvement measures within
healthcare facilities targeted toward asthma management are encouraged, as is
surveillance of disparities within healthcare facilities.31
conclusion
The burden of uncontrolled asthma is
significant. Asthma-related hospitalizations and impairments in quality of life
continue to affect those diagnosed with
the disease and the healthcare system
at large. Successful asthma management therefore centers on achieving and
maintaining symptom control. Assessment of asthma control requires timely
and frequent evaluation with appropriate modifications to pharmacotherapy
as recommended in clinical practice
guidelines. Medication adherence also
DrugTopics .c om
continuing education
needs to be addressed at each point of
patient contact to ensure that asthma
outcomes are met. Multidisciplinary,
team-based approaches that take into
consideration strategies to reduce health
disparities are encouraged and are believed to be a key factor in the manage-
ment of asthma. Pharmacists are well
trained and highly accessible to lend
clinical decision support and other services for the management of asthma.•
The references are available online at
www.drugtopics.com/cpe.
For immediate CPE credit,
take the test now online at
www.drugtopics.com/cpe
Once there, click on the link below
Free CPE Activities
test questions
1. Which of the following illustrates an example of
risk reduction as it relates to asthma control?
a. Using a short-acting rescue inhaler < 2
days/week
b. Preventing progressive loss of lung function
c. Maintaining near-normal pulmonary function
d. Minimizing chronic troublesome
symptoms
2. Which of the following patient groups should
have an asthma action plan?
a. Children aged four years and younger
b. Children aged five to 11 years
c. Patients aged 12 years and older
d. All age groups should have a written
asthma action plan
3. When should a patient with poorly controlled
asthma for whom therapy has been adjusted
follow up for reassessment of asthma
control?
a. One month
b. Six months
c. Two weeks
d. Two to six weeks
4. Which of the following statements regarding
pediatric and adult asthma is TRUE?
a. Objective measurement of lung function
(eg, spirometry) is often unreliable in children.
b. The prevalence of asthma is highest in
adults aged 45 to 65 years.
c. Asthma symptoms are chronic in children.
d. Asthma is the leading cause of
hospitalizations in adults.
5. What “zone” is a patient in if he or she can
perform usual activities without exhibiting
symptoms of asthma?
a. White zone
b. Green zone
c. Yellow zone
d. Red zone
6. How many months should asthma be
controlled before therapy is stepped down?
a. At last one month
b. At least three months
c. At least six months
d. At least one year
DrugTopics .c om
7. Which of the following factors is least likely
to contribute to nonadherence of asthma
medications?
a. Fear of unwanted side effects
b. Regimen complexity
c. Lack of understanding of disease severity
d. Comorbid cardiovascular disease
8. Which of the following interventions would
be best for a patient who does not take his
or her asthma medication because he or she
“doesn’t feel like it’?
a. Simplifying the medication regimen
b. Setting an alarm to alert when it is time
for the next dose
c. Using motivational interviewing techniques
d. Referring the patient to a asthma specialist
9. Classify the level of asthma control for a
25-year-old patient with the following: ACT
score of 12; rescue inhaler use four times/
day; some limitation with usual activities.
a. Well controlled
b. Not well controlled
c. Very poorly controlled
d. Medical emergency
10. Which of the following statements is TRUE
regarding asthma management?
a. Initial pharmacotherapy selection is based
on control; adjustments are based on severity.
b. The preferred treatment option for
persistent asthma is inhaled corticosteroids
for adults and long-acting beta-agonists for
children.
c. Treatment recommendations for all age
groups are based on randomized control trials.
d. At minimum, asthma control should be
assessed at one- to six-month intervals.
11. Which of the following therapies is the
treatment of choice for exercise-induced
bronchoconstriction?
a. Albuterol b. Ciclesonide
c. Ipratropium d. Fluticasone
12. Which of the following drug therapies is
considered a preferred therapy for persistent
asthma in patients aged 12 years and older?
a. Budesonide b. Omalizumab
c. Montelukast d. Theophylline
13. A common side effect of albuterol is:
a. Arrhythmias b. Chest pain
c. Dry mouth d. Hyperglycemia
14. _______ carries a black-box warning
advising patients not to use the drug as
monotherapy in asthma without an inhaled
corticosteroid.
a. Ipratropium b. Salmeterol
c. Levalbuterol d. Omalizumab
15. Omalizumab is best described as:
a. A leukotriene receptor modifier
b. An anti-IgE monoclonal antibody
c. An anticholinergic
d. A long-acting beta-agonist
16. Which of the following leukotriene receptor
modifiers is least likely to be involved in
clinically significant drug interactions?
a. Zileuton
b. Montelukast
c. Zafirlukast d. None of the above
17. An alternative rescue inhaler in patients who
cannot tolerate the first-line SABA therapy is:
a. Albuterol b. Salmeterol
c. Formoterol d. Ipratropium
18. A standard adult dose of prednisone for a
short “burst” of therapy is
a. 40 mg by mouth daily for five days
b. 80 mg by mouth daily for three days
c. 10 mg by mouth daily for 15 days
d. 30 mg by mouth daily for seven days
19. Health disparities in asthma are found in
which of the following populations?
a. Caucasians
b. Pregnant women
c. African Americans
d. High-income societies
20. Which intervention(s) could be implemented
to help reduce health disparities in asthma?
a. Improve community awareness of asthma
b. Provide translator services during
clinician visits
c. Conduct surveillance of health disparities
d. All of the above
May 2015
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MtM eSSentiaLS FoR aStHMa ManageMent: PaRt 2
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