review

Managing Asthma in Primary Care

Managing Asthma in Primary Care:

Putting New Guideline Recommendations Into Context
Michael E. Wechsler, MD
Many patients with asthma are treated in the primary care setting. The primary care physician is therefore in a key position to
recognize poorly controlled asthma and to improve asthma management for these patients. However, current evidence continues
to show that, for a substantial number of patients, asthma control
is inadequate for a wide variety of reasons, both physician-related
and patient-related. The most recently updated treatment guidelines from the National Asthma Education and Prevention Program
were designed to help clinicians, including primary care physicians, manage asthma more effectively with an increased focus
on achieving and maintaining good asthma control over time. The
current review is intended to assist primary care physicians in
improving asthma control among their patients; this review clarifies the new guidelines and provides a specialists perspective
on diagnosis, appropriate therapy, disease control surveillance,
and appropriate referral when necessary. This discussion is based
primarily on the new guidelines and the references cited therein,
supplemented by the authors own clinical experience.
Mayo Clin Proc. 2009;84(8):707-717
ACT = Asthma Control Test; EPR3 = Expert Panel Report 3; FeNO =
fractionated exhaled nitric oxide; ICS = inhaled corticosteroid; LABA =
long-acting -agonist; NAEPP = National Asthma Education and Prevention Program; RAST = radioallergosorbent test

rimary care physicians treat a considerable number

of patients with asthma. These physicians are wellpositioned to recognize inadequately controlled asthma
and to improve disease management for many patients
with asthma. However, evidence continues to show that,
for a substantial number of patients, asthma control is
inadequate.1-4 In a study of US national administrative
claims data, nearly three-fourths of patients with asthma
(73%; 46,227/63,324) met the criteria for uncontrolled
disease at least once during a 3-year period.3
A wide range of factors, physician-related and patientrelated, can contribute to poor asthma control. One aspect
of this problem, as revealed by data from patient surveys,
is that many patients overestimate their level of disease
control, often tolerating substantial asthma symptoms
and having low expectations about the degree of control
that is possible.5,6 Patients also frequently exhibit poor
adherence to prescribed controller medications7; additional
patient-related factors affecting asthma control include selfmanagement abilities, smoking status, inhaler technique,
ability to remember doses, access to prescriptions, and costs
of medication.6
Physician practices can also contribute to inadequate
asthma control. Physicians have a tendency to underestimate
the prevalence of asthma symptoms and to overestimate
the degree to which their patients asthma is controlled1,6;
Mayo Clin Proc.

therefore, they may not always prescribe adequate controller

medication therapy.7 Physicians may also have an inadequate
understanding of disease etiology or may not communicate
well with patients, and these problems make it difficult to
establish a pharmacotherapeutic regimen that the patient is
willing and able to follow.5
In light of the complexities inherent in the longterm management of asthma, national and international
guidelines have been developed over the years to assist
clinicians in caring for their patients. The use of guidelinebased treatment strategies has been shown to favorably
affect asthma outcomes, but there has
also been increasing recognition that For editorial
previous guidelines were not adequately comment,
followed and did not lead to acceptable see page 673
levels of asthma control.8 In 2007,
the National Asthma Education and Prevention Program
(NAEPP) issued updated guidelines for the diagnosis
and management of asthma (the Expert Panel Report 3
[EPR3]),9 which, among other changes, shifted the focus
to ongoing assessment of disease control with the goal
of improving the management of asthma over time. The
current review is intended to assist primary care physicians
in improving their patients asthma control, in part through
an improved understanding of the new guidelines, and to
provide a specialists perspective on diagnosing asthma and
prescribing appropriate therapy, monitoring disease control,
and providing appropriate and timely referrals. As such, this
review is based primarily on the NAEPP guidelines, the
references therein, and the authors clinical experience.
Overview of the Updated NAEPP Guidelines
The NAEPP, initiated by the National Heart, Lung, and
Blood Institute in 1989 in response to the worsening asth
From the Division of Pulmonary and Critical Care Medicine, Brigham and
Womens Hospital, Harvard Medical School, Boston, MA.
From 2007 to 2009, Dr Wechsler consulted for or participated in advisory
boards or speakers bureaus for AstraZeneca, GlaxoSmithKline, ScheringPlough, Novartis, Genentech, Merck, MediciNova, and Sepracor.
This article is freely available on publication, because the authors have chosen the immediate access option.
Individual reprints of this article are not available. Address correspondence to
Michael E. Wechsler, MD, Pulmonary and Critical Care Medicine, Brigham and
Womens Hospital, Harvard Medical School, 15 Francis St, PBB Lobby, Boston,
MA 02115 (mwechsler@partners.org).
2009 Mayo Foundation for Medical Education and Research

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Managing Asthma in Primary Care

TABLE 1. Key Indicators for Considering a Diagnosis of Asthmaa

Wheezing
High-pitched whistling sounds when breathing out, especially in
children. (Lack of wheezing and normal findings on chest
examination do not exclude asthma.)
History of any of the following
Cough, worse particularly at night
Recurrent wheeze
Recurrent difficulty in breathing
Recurrent chest tightness
Symptoms occur or worsen in the presence of the following
Exercise
Viral infection
Animals with fur or hair
House-dust mites (in mattresses, pillows, upholstered furniture,
carpets)
Mold
Smoke (tobacco, wood)
Pollen
Changes in weather
Strong emotional expression (laughing or crying hard)
Airborne chemicals or dusts
Menstrual cycles
Symptoms occur or worsen at night, awakening the patient
a

Consider a diagnosis of asthma and performing spirometry if any of these

indicators is present. These indicators are not diagnostic in themselves, but
the presence of multiple key indicators increases the probability of a
diagnosis of asthma. Spirometry is needed to establish a diagnosis of asthma. Eczema, hay fever, and a family history of asthma or atopic diseases
are often associated with asthma, but they are not key indicators.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

domains of current impairment and future risk, which are

to be noted by the physician during the assessment of both
asthma severity and disease control, so that asthmas effects
on quality of life and functional capacity in the present and
its risks for the future are considered separately.9
Regarding medication management, the most sub
stantive changes in the EPR3 guidelines are the separate
recommendations for 3 age groups of patients (children
aged birth to 4 years, children aged 5 to 11 years, or patients
aged 12 years or older) and the expansion of treatment
steps from 4 to 6 so that the action within each step can
be simplified.9,11,12 In terms of specific medications, the
important role of inhaled corticosteroids (ICSs) in asthma
therapy continues to be supported. On the basis of new
safety data for long-acting -agonists (LABAs), guidelines
recommend equal consideration for either increasing the
ICS dose to a medium dose or adding a LABA to lowdose ICS therapy for patients aged 12 years or older whose
asthma is inadequately controlled by low-dose ICS therapy.
LABAs should not be used as monotherapy. Finally, the
use of allergy immunotherapy has been included in steps 2
through 4 for patients aged 5 years or older, and omalizumab
has been included for consideration in therapy steps 5 and
6 for patients aged 12 years or older.9
MAKING THE DIAGNOSIS

ma epidemic, issued its first set of asthma management

guidelines in 1991. A revised set of guidelinesthe Expert
Panel Report 2was published in 1997 and was updated
in 2002. These guidelines first introduced the stepwise
approach to asthma therapy that is based on a 4-part
classification scheme of disease severity (mild intermittent,
mild persistent, moderate persistent, or severe persistent).
Although this approach is useful, its limitations have been
clearly recognized, particularly the need to more clearly
address the fluctuating severity of asthma symptoms over
time.8,10,11 Thus, the EPR3 guidelines, published in 2007,
were based on the overall stepwise treatment model but
incorporated some fundamental changes.
A key modification in the EPR3 guidelines is the
emphasis on distinguishing between asthma severity, which
is intrinsic to the disease process, and a patients level of
asthma control, which fluctuates over time. Classifying
disease severity is the first step in initiating therapy for
a patient who has not been taking long-term control
medication. Once therapy is initiated, the emphasis shifts to
the assessment of asthma control, which will guide decisions
about maintaining or adjusting therapy and evaluating the
patients responsiveness to various asthma medications.9
The new guidelines also added a distinction between the
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Mayo Clin Proc.

Correctly diagnosing asthma is the first step toward attain

ing disease control. In general, a diagnosis of asthma is
established if episodic symptoms of airflow obstruction or
airway hyperresponsiveness are present, airflow obstruction
is at least partially reversible, and alternative diagnoses are
excluded. The guidelines recommend the use of a detailed
medical history, the results of a physical examination
(focusing on the upper respiratory tract, chest, and skin), and
the results of spirometry (for patients aged 5 years or older)
in making the diagnosis. Any additional studies necessary
for excluding alternative diagnoses or identifying other
potential causes of symptoms should also be performed
(eg, chest radiography, specific blood tests).9 However,
primary care physicians may choose to refer patients to a
specialist for spirometry or other testing.
Table 1 lists some key indicators of a diagnosis of asthma,
including wheezing; a history of recurrent cough, wheezing,
difficulty in breathing, or chest tightness; and symptoms
that occur or worsen in the presence of specific triggers.9
Particularly important factors that should be addressed
as part of the medical history include the overall pattern
of symptoms (eg, perennial, seasonal, or both; continual,
episodic, or both; diurnal variations), precipitating factors
(such as the presence of allergic triggers), and a family
history of asthma, allergy, or other atopic disorders.9

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Managing Asthma in Primary Care

TABLE 2. Differential Diagnostic Possibilities for Asthma

Infants and children
Upper airway diseases
Allergic rhinitis and sinusitis
Obstructions involving large airways
Foreign body in trachea or bronchus
Vocal cord dysfunction
Vascular rings or laryngeal webs
Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
Enlarged lymph nodes or tumor
Obstructions involving small airways
Viral bronchiolitis or obliterative bronchiolitis
Cystic fibrosis
Bronchopulmonary dysplasia
Heart disease
Other causes
Recurrent cough not due to asthma
Aspiration due to dysfunction of the swallowing mechanism or
to gastroesophageal reflux
Adults
Chronic obstructive pulmonary disease (eg, chronic bronchitis or
emphysema)
Congestive heart failure
Pulmonary embolism
Mechanical obstruction of the airways (benign and malignant
tumors)
Pulmonary infiltration with eosinophilia
Cough resulting from administration of drugs (eg, angiotensin converting enzyme inhibitors)
Vocal cord dysfunction
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

Although recurrent cough and wheezing are often

due to asthma, other causes of airway obstruction should
be considered in the initial diagnosis or if the patient
does not respond to initial therapy. Table 2 lists the most
common possibilities included in the differential diagnosis
of asthma, according to the EPR3 guidelines. Vocal cord
dysfunctioncharacterized by episodic dyspnea and
wheezing caused by intermittent paradoxical vocal cord
adduction during inspirationoften mimics asthma and
can be difficult to diagnose. A diagnosis is best made
with indirect or direct vocal cord visualization during an
episode, and treatment generally consists of speech therapy
and relaxation techniques.
Several other conditions may coexist with asthma
or complicate the diagnosis or management of asthma.
Cough-variant asthma, in particular, is easily overlooked
because chronic cough can be a sign of a wide variety of
health problems. Conversely, chronic cough may also be
the principal (or only) manifestation of asthma, especially
among young children. The diagnosis of cough-variant
asthma is confirmed by a positive response to asthma
medication, and treatment should follow the usual stepwise
approach to asthma management.
Other common comorbid conditions that complicate the
diagnosis of asthma are chronic sinusitis, gastroesophageal
reflux disease, obstructive sleep apnea, and respiratory
Mayo Clin Proc.

tract infections. Because it is often accompanied by

symptoms similar to those of asthma and by elevated IgE
levels, allergic bronchopulmonary aspergillosis should also
be excluded.9,13 Although rare, Churg-Strauss syndrome is
another comorbid condition that should be considered in the
assessment of patients with difficult-to-control asthma. It is a
serious disorder characterized by eosinophilic inflammation
of the respiratory tract and necrotizing vasculitis of small
and medium vessels. Laboratory results demonstrate eosin
ophilia, and symptoms include asthma, rhinosinusitis, pul
monary infiltrates, peripheral neuropathy, and skin, heart, or
gastrointestinal involvement.14
MANAGING ASTHMA
How Are Asthma Severity and Control Assessed
and Monitored?
Once the diagnosis of asthma has been established, the
focus shifts to classifying asthma severity so that therapy
can be initiated and to monitoring control over time so that
therapy can be adjusted. According to the new guidelines,
severity and control should be assessed separately, but
both are classified on the basis of the domains of current
impairment and future risk. Impairment is defined as
the frequency and intensity of symptoms and functional
limitations the patient is experiencing currently or has
recently experienced, whereas risk is defined as the
likelihood of either asthma exacerbations, progressive
decline in lung function (or, for children, lung growth),
or risk of adverse effects from medication. The new
guidelines stress that the impairment domain and the risk
domain may respond differently to treatment.9
In assessing impairment, asthma severity should be
evaluated using the categories outlined in Figure 1.9
Severity should be assigned according to the most severe
category of impairment. Assessment of future risk, which
is based on the frequency of exacerbations requiring the
administration of oral systemic corticosteroids, is another
important facet of asthma severity. The occurrence of
exacerbations can vary widely (from rare to frequent) among
patients and for each individual patient. Because patients at
any level of disease severity, including intermittent asthma,
can experience severe exacerbations, the current version of
the guidelines has omitted the word mild from the former
classification of mild intermittent asthma.
Although the current guidelines state that evidence is
insufficient to confirm an association between the frequency
of exacerbations and the level of asthma severity, in general,
the more frequent and the more intense the exacerbations,
the greater the degree of underlying disease severity.9,15
One study found that the rates of hospitalizations, urgent
care visits, and absenteeism for patients with moderate

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Managing Asthma in Primary Care

Classification of asthma severity

(patients aged 12 y or older)
Components of severity
Persistent

Intermittent

Impairment
Normal FEV1/FVC:
8-19 y 85%
20-39 y 80%
40-59 y 75%
60-80 y 70%

Risk

Mild

Moderate

Severe

Daily

Throughout the day

>1 time/wk
but not nightly

Often 7 times/wk

Daily

Several times
per day

Some limitation

Extreme limitation

FEV1 >60% but

<80% of predicted
FEV1/FVC reduced
5%

FEV1 <60% of
predicted
FEV1/FVC reduced
>5%

Symptoms

2 d/wk

>2 d/wk
but not daily

Nighttime
awakenings
Short-acting
2-agonist use for
symptom control
(not for prevention
of EIB)

2 times/mo

3-4 times/mo

2 d/wk

Interference with
normal activity

None

Lung function

Normal FEV1
between
exacerbations
FEV1 >80% of
predicted
FEV1/FVC normal

Exacerbations
requiring oral
systemic
corticosteroids

>2 d/wk but not

daily, and not
>1 time/d
Minor limitation

FEV1 >80% of
predicted
FEV1/FVC normal
2/y
2/ya

0-1/ya
0-1/y

Consider severity and interval since last exacerbation. Frequency and

severity may fluctuate over time for patients in any severity category.
Relative annual risks of exacerbations may be related to FEV1

The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient needs.
Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patients/caregivers
recall of previous 2-4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In
general, more frequent and intense exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or ICU admission)
indicate greater underlying disease severity. For treatment purposes, patients who had 2 exacerbations requiring oral systemic
corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of
impairment levels consistent with persistent asthma.

FIGURE 1. Assessing asthma severity. EIB = exercise-induced bronchospasm; FEV1 = forced expiratory volume in 1 second; FVC =
forced vital capacity; ICU = intensive care unit.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

to severe persistent asthma were 2-fold to 4-fold higher

than those for patients with mild intermittent asthma.15 For
the purposes of classification, the guidelines specify that
patients who have experienced 2 or more exacerbations
requiring the administration of oral corticosteroids during
the past year are considered to have persistent asthma, even
if all of the impairment categories suggest that they have
intermittent asthma.9
After disease severity has been assigned, treatment
can be initiated at the recommended step. If the patient is
already receiving asthma therapy, symptom control should
be periodically monitored according to the same domains
of impairment and risk (with additional categories for
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Mayo Clin Proc.

each domain; see What Does Good Asthma Control Look

Like?). Assessment of control is used to guide alterations
in therapy according to the stepwise approach (also
discussed hereinafter). Minimally invasive markers, such
as fractionated exhaled nitric oxide (FeNO) levels and
sputum eosinophil counts, may also be useful for assessing
asthma control, monitoring medication adherence, and
adjusting therapy; however, the guidelines suggest that
further evaluation of these measures is necessary before
they can be considered to be tools for routine management.9
Nevertheless, FeNO has been used for asthma diagnosis,
as a rapid response marker of corticosteroid treatment,
and as an indicator of asthma control.16 The expanded

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Managing Asthma in Primary Care

availability of portable FeNO monitors, combined with an

improved ability to interpret the clinical meaning of the
measurements, is likely to expand the role of minimally
invasive markers in the future.
What Are the Obstacles to Achieving Good
Asthma Control?
Ongoing monitoring of symptom control is a key component
of asthma management over time and helps ensure that
treatment goals are met and necessary adjustments to
therapy are made. However, one of the difficulties of asthma
management is that both patients and physicians tend to
underestimate the severity of symptoms or overestimate the
patients level of disease control. Many patients may assume
that a certain level of symptoms or some limitation of activity
is an inevitable consequence of having asthma. In fact, 39%
to 70% of respondents to the Asthma Insights and Reality
(AIR) surveys reported that their asthma was well controlled
or completely controlled even though they were experiencing
moderate symptoms.2 Thus, patients whose asthma is poorly
controlled may not always receive a prescription for adequate
controller medication therapy or may not adhere to a daily
controller medication regimen. Fewer than one-third of the
respondents to the AIR surveys, including those with severe
persistent asthma, reported regular use of preventive asthma
medication; usage rates ranged from 26% in Western Europe
to 9% in Japan.2 A review of several different patient surveys
found that at least 40% of patients reported underusing their
prescribed medications, in terms of either frequency or
dosing, largely because of discomfort with long-term ICS
therapy. In fact, when higher ICS doses were prescribed for
regaining asthma control, at least 50% of patients reported
that they refused to fully adhere to the higher dosage
regimen because of concerns about adverse effects.5 In other
circumstances, patients do not even use their inhalers with
proper technique, further preventing them from gaining the
benefit of these therapies or from achieving control.
Other obstacles to achieving good asthma control
include the presence of exacerbating factors, such as
ongoing occupational or allergen exposures, which should
be identified and eliminated when possible. Occupational
history should be considered for adults with uncontrolled
asthma, especially if symptoms improve on weekends and
holidays. Perhaps the environmental factor that contributes
most to the development, persistence, and severity of
asthma is viral respiratory infection. Although influenza
vaccination is recommended for patients with asthma
because of their risk of influenza-associated complications,
vaccination should not be expected to reduce the frequency
or severity of exacerbations during influenza season.9
Asthma can also be exacerbated by certain drugs, such
as nonsteroidal anti-inflammatory drugs and -blockers.
Mayo Clin Proc.

Aspirin-sensitive asthma is frequently associated with

a genetic sequence variation and is relatively common
in Eastern Europe and Japan. Although the mechanism
involved in -blockerinduced asthma is not completely
understood, antagonism of the 2-adrenoreceptor, even with
1-selective medications, should be avoided for patients
with asthma.17 Asthma may also be difficult to control in
the presence of untreated gastroesophageal reflux disease
or other comorbid conditions.
What Does Good Asthma Control Look Like?
Both patients and their physicians should understand
exactly what constitutes good asthma control. Physicians
must be able to recognize good control, or the lack thereof,
so that they can adjust the management plan. Patients should
be educated so that they do not accept a certain level of
ongoing symptoms, short-acting inhaler use, and reduced
activity as normal for someone with asthma. Figures
2, 3, and 4 detail the impairment and risk criteria that are
used in the EPR3 guidelines to classify asthma as wellcontrolled, not well-controlled, or very poorly controlled
for patients in 3 age groups. A patient aged 12 years or older
who has well-controlled asthma should have symptoms no
more than twice per week, should experience nighttime
awakenings no more than twice per month, should use a
short-acting -agonist no more than twice per week, should
experience no interference with normal activity, should
have a forced expiratory volume in 1 second or peak flow
levels higher than 80% of the predicted or personal best,
and should have had no more than 1 exacerbation during
the past year.9 If any aspect of the patients asthma control
does not meet these criteria, the patient does not have good
asthma control, and the clinician should consider changing
the patients asthma management plan.
In addition to clinician assessment, several validated
self-assessment tools can be used during follow-up visits
to quickly capture the overall level of asthma control
from the patients perspective. These tools are based on
current impairment and do not address the risk domain of
control. The most commonly used tools are the Asthma
Control Questionnaire,18 the Asthma Therapy Assessment
Questionnaire,19 and the Asthma Control Test (ACT).20
The ACT is an easy-to-use questionnaire consisting of 5
questions, each scored by the patient on a scale from 1 to 5,
regarding activity levels, frequency of daytime or nighttime
symptoms, rescue inhaler use, and the patients perception
of asthma control during the past 4 weeks. The result is a
total numeric score ranging from 5 to 25; a cutpoint score
of 20 or higher generally indicates well-controlled asthma
(in conjunction with the physicians clinical assessment).
A validation study of the ACT found that higher cutpoint
scores had higher sensitivity but lower specificity (falsely

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Managing Asthma in Primary Care

Classification of asthma control

(children aged 0-4 y)

Components of control

Impairment

Well-controlled

Not
well-controlled

Very poorly
controlled

Symptoms

2 d/wk

>2 d/wk

Throughout
the day

Nighttime awakenings

1 time/mo

>1 time/mo

>1 time/wk

Interference with
normal activity

None

Some limitation

Extreme limitation

Short-acting 2-agonist
use for symptom control
(not for prevention of EIB)

2 d/wk

>2 d/wk

Exacerbations requiring oral

systemic corticosteroids

0-1/y

2-3/y

Risk
Treatment-related adverse
effects

Several times
per day
>3/y

Adverse effects of medication can vary in intensity from none to

very troublesome and worrisome. The level of intensity is not
correlated with the level of control but should be considered in
the overall assessment of risk.

FIGURE 2. Assessing asthma control. Criteria for well-controlled, not well-controlled, or very poorly controlled
asthma in children aged 0 to 4 years. Level of control is based on the most severe impairment or risk category. Assessment of the impairment domain is based on the patients (or caregivers) recall of incidents
during the previous 2 to 4 weeks. Symptom assessment over longer periods should reflect a global assessment, such as determining whether the patients asthma is better or worse since the last visit. EIB =
exercise-induced bronchospasm.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9
Classification of asthma control
(children aged 5-11 y)
Components of control

Impairment

Well-controlled

Not
well-controlled

Very poorly
controlled

Symptoms

2 d/wk but not more

than once each day

>2 d/wk or multiple

times on 2 d/wk

Throughout the day

Nighttime awakenings

1 time/mo

2 times/mo

2 times/wk

Interference with normal activity

None

Some limitation

Extreme limitation

Short-acting 2-agonist
use for symptom control
(not for prevention of EIB)

2 d/wk

>2 d/wk

Several times per day

>80% of predicted/
personal best
>80%

60%-80% of predicted/
personal best
75%-80%

Lung function
FEV1 or peak flow
FEV1/FVC

Exacerbations requiring oral

systemic corticosteroids
Risk

0-1/y

<60% of predicted/
personal best
<75%

2/y

Consider severity and interval since last exacerbation

Reduction in lung growth

Evaluation requires long-term follow-up

Treatment-related
adverse effects

Adverse effects of medications can vary in intensity from none to very

troublesome and worrisome. The level of intensity is not correlated with the
level of control but should be considered in the overall assessment of risk.

FIGURE 3. Assessing asthma control. Criteria for well-controlled, not well-controlled, or very poorly controlled asthma in children
aged 5 to 11 years. Level of control is based on the most severe impairment or risk category. Assessment of the impairment
domain is based on the patients (or caregivers) recall of incidents during the previous 2 to 4 weeks and by spirometry or peak
flow measures for patients aged 5 years or older. Symptom assessment over longer periods should reflect a global assessment,
such as determining whether the patients asthma is better or worse since the last visit. EIB = exercise-induced bronchospasm;
FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

712

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Managing Asthma in Primary Care

Classification of asthma control

(patients aged 12 y or older)

Components of control
Well-controlled

Not
well-controlled

Very poorly
controlled

2 d/wk

>2 d/wk

Throughout the day

Symptoms

Impairment

Nighttime awakenings

2 times/mo

1-3 times/wk

4 times/wk

Interference with normal activity

None

Some limitation

Extreme limitation

Short-acting 2-agonist
use for symptom control
(not for prevention of EIB)

2 d/wk

>2 d/wk

Several times per day

FEV1 or peak flow

>80% of predicted/
personal best

60%-80% of
predicted/personal
best

<60% of predicted/
personal best

0
0.75a
20

1-2
1.5
16-19

3-4
N/A
15

Validated questionnaires
ATAQ
ACQ
ACT

0-1/y

Exacerbations
Risk

2/y

Consider severity and interval since last exacerbation

Evaluation requires long-term follow-up care

Progressive loss of lung function

Treatment-related
adverse effects

Adverse effects of medication can vary in intensity from none to very

troublesome and worrisome. The level of intensity is not correlated with the
level of control but should be considered in the overall assessment of risk.

FIGURE 4. Assessing asthma control. Criteria for well-controlled, not well-controlled, or very poorly controlled asthma in children aged 12
years or older. Level of control is based on the most severe impairment or risk category. Assessment of the impairment domain is based
on the patients (or caregivers) recall of incidents during the previous 2 to 4 weeks and by spirometry or peak flow measures for patients
aged 5 years or older. Symptom assessment over longer periods should reflect a global assessment, such as determining whether the
patients asthma is better or worse since the last visit. ACQ = Asthma Control Questionnaire; ACT = Asthma Control Test; ATAQ = Asthma
Therapy Assessment Questionnaire; EIB = exercise-induced bronchospasm; FEV1 = forced expiratory volume in 1 second.
a
ACQ values of 0.76-1.4 are inconclusive regarding well-controlled asthma.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

identifying some controlled cases as uncontrolled) in de

tecting uncontrolled asthma, whereas lower cutpoint scores
had lower sensitivity but higher specificity. Agreement
between the ACT score and the rating of an asthma specialist
was 69.5% at a cutpoint score of 20 or lower.20 In addition
to providing the patients perspective on asthma control, this
assessment tool also provides the clinician with a numeric
value (a vital sign for asthma control) that can be tracked
over time in the patients asthma management plan. One
limitation of the existing instruments for measuring asthma
control is that they are generally based on patients selfreports of symptoms during the previous 4 weeks and do
not incorporate long-term symptoms or activity limitations.
Therefore, they may underestimate the effect of asthma on
patients lives.15

How Asthma Control Can Be Improved: Managing Asthma
Pharmacotherapy
Many medications are available for the management of
asthma, and it is beyond the scope of this article to provide
Mayo Clin Proc.

a comprehensive review of them. An overview of the main

classes of medication and their uses is provided in Table 3,
and the 6-part stepwise approach to asthma management
included in the EPR3 guidelines is shown in Figure 5 (please
refer to the guidelines for specific steps for the age groups
of children aged 0 to 4 years and children aged 5 to 11
years).9 In brief, ICSs are general anti-inflammatory agents,
targeting the airway inflammation that is a key component
of the asthma disease process, whereas -agonists (both
short-acting and long-acting) are bronchodilators with a
different but complementary mechanism of action (targeting
bronchoconstriction of the airway smooth muscle). Shortacting -agonists provide quick symptom relief, whereas
LABAs act as long-term control agents and are used in
conjunction with ICS therapy. Leukotriene modifiers,
which block the leukotriene pathway (proinflammatory
lipid mediators that promote airway smooth muscle
contraction, among other inflammatory activities), show
both modest anti-inflammatory and bronchodilating ac
tivity.21 Omalizumab is a recombinant humanized mono

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Managing Asthma in Primary Care

TABLE 3. Overview of Classes of Asthma Medications

Medication class

Examples

Mechanism

Mode of administration

Long-term controller medications

ICSs
Budesonide
Anti-inflammatory
Inhaled once or twice daily

Beclomethasone

Ciclesonide

Flunisolide

Fluticasone

Mometasone

Triamcinolone
LABAs
Salmeterol
Bronchodilator
Inhaled twice daily

Formoterol
Combination
Salmeterol/fluticasone
Combination anti-inflammatory/ Inhaled twice daily
LABA/ICS
Formoterol/budesonide bronchodilator
Inhaled twice daily
Leukotriene modifiers Montelukast
Anti-inflammatory and
Oral (once daily for montelukast,

Zileuton bronchodilatory effects twice daily for zileuton)
Immunomodulators
Anti-IgE
Omalizumab
Immunomodulatory/
SC injection once every 2
anti-inflammatory or 4 weeks
Mast cell stabilizers
Cromolyn/nedocromil
Anti-inflammatory (stabilizes
Inhaled 4 times daily
mast cells and interferes with
chloride channel function)
Methylxanthines
Theophylline
Bronchodilators; may have
Oral (liquid, sustained-release
mild anti-inflammatory effects tablets, and capsules)
Quick-relief agents
SABAs
Albuterol
Bronchodilator
Inhaled every 4-6 h as needed

Levalbuterol

Pirbuterol
Anticholinergics
Ipratropium bromide
Bronchodilator (inhibits
Inhaled every 6 h during moderate
muscarinic cholinergic or severe asthma exacerbations
receptors), reduces intrinsic
vagal tone of the airways
Oral corticosteroids
Methylprednisolone
Anti-inflammatory
Oral (often given in short-course

Prednisolone bursts during exacerbations)

Prednisone
ICS = inhaled corticosteroid; LABA = long-acting -agonist; SABA = short-acting -agonist; SC = subcutaneous.
Data from Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

clonal anti-IgE antibody that specifically binds to free IgE,

the immunoglobulin molecule that triggers the allergic
cascade by binding to effector cells such as mast cells
and basophils. Thus, for patients with allergic asthma,
omalizumab blocks the subsequent downstream cascade of
events triggered by IgE, including inflammatory effects in
the airways.21
For patients with persistent asthma, regardless of age
group, daily anti-inflammatory treatment with ICSs is still
the cornerstone of therapy. As already discussed, one of
the key changes in EPR3 from previous guidelines is the
recognition of potential safety concerns associated with
LABA therapy; therefore, at step 3 (for patients aged 5
years or older), patients whose asthma was not adequately
controlled with low-dose ICSs should be stepped up to
either medium-dose ICS therapy or low-dose ICS therapy
plus a LABA. Most importantly, LABAs are to be used
only in combination with ICS therapy; the Food and Drug
Administration has issued a black-box warning against
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Mayo Clin Proc.

the use of LABAs as monotherapy for long-term control

of asthma.9 An additional change in the EPR3 guidelines is
the addition of anti-IgE therapy with omalizumab at steps
5 and 6 (patients who are being treated with a high-dose
ICS plus a LABA) as an option for patients aged 12 years
or older who have IgE-mediated allergic asthma (patients
with a clinical history of allergies and evidence of elevated
IgE levels in conjunction with positive results from a skin
test or a radioallergosorbent test [RAST]). Omalizumab is
indicated for patients aged 12 years or older with moderate to
severe persistent asthma whose symptoms are inadequately
controlled with ICSs and who have exhibited a positive skin
test reaction or in vitro reactivity to a perennial aeroallergen
(via RAST). Although the cost of this biologic agent
is higher than that of other asthma therapies, it has been
shown to reduce the incidence of asthma exacerbations,
even among patients with more severe asthma.
Regardless of the therapy step, long-term management
of asthma always involves a balance between the benefits

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Managing Asthma in Primary Care

Step 5
Preferred:

Step 4
Step 3
Step 2
Low-dose ICS

Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:

Alternative:

Preferred:

Step 1
Preferred:
SABA as needed

Preferred:

Cromolyn, LTRA,
nedocromil, or
theophylline

Low-dose ICS +
LTRA,
theophylline, or
zileuton

High-dose
ICS + LABA

Preferred:
Medium-dose
ICS + LABA

Alternative:
Mediium-dose
ICS + LTRA,
theophylline, or
zileuton

Step 6
Preferred:
High-dose ICS +
LABA + oral
corticosteroid

AND

AND

Consider
omalizumab for
patients with
allergies

Consider
omalizumab for
patients with
allergies

Step up if
needed
(rst, check
adherence,
inhaler
technique, and
environmental
control)

Assess
control
Step down if
possible

Each step: Patient education, environmental control, and management of comorbid conditions
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients with allergic asthma

(and if asthma
is wellcontrolled
at least 3 mo)

Quick-relief medication for all patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: as many as
3 treatments at 20-min intervals as needed. Short course of oral systemic corticosteroids may be
needed. Use of SABA >2 d/wk for symptom relief (not for prevention of EIB) generally indicates
inadequate control and the need to step up treatment

FIGURE 5. Stepwise approach for managing asthma in patients aged 12 years or older. EIB = exercise-induced bronchospasm; ICS =
inhaled corticosteroid; LABA = long-acting -agonist; LTRA = leukotriene receptor antagonist; SABA = short-acting -agonist.
From Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.9

of achieving the best symptom control possible (hence

minimizing the risks of uncontrolled asthma and the effect
of asthma on the patients well-being) and the risks of
adverse effectsa balance recognized as part of the risk
domain of the updated EPR3 guidelines. At low doses,
ICS therapy is generally considered safe, and its benefits
are thought to outweigh its risks for most patients with
persistent asthma. However, patients concerns about longterm corticosteroid use may affect their adherence to a
prescribed regimen, and the risks of systemic effects (eg,
reduced linear growth rate in children or lower bone mineral
density in adults) increase with higher doses.22 Therefore,
it is just as important to step down medication for patients
with well-controlled asthma as to step up medication for
those with uncontrolled asthma.
Primary care physicians should be mindful that higher
doses of ICSs for a particular patient may provide little
added benefit when weighed against the increased risk
of systemic effects. For example, a meta-analysis of
Mayo Clin Proc.

randomized trials studying the effectiveness of fluticasone

for adolescents and adults with moderate to severe asthma
found that the greatest clinical benefit was observed at a
dose of 200 g/d. Only minimal additional improvement
was seen at doses of 500 or 1000 g/d, although there was
a considerable level of individual patient variability.23 The
situation is further complicated by the observation that as
many as one-third of patients with asthma may have some
degree of corticosteroid insensitivity and thus may not
exhibit an adequate clinical response even to high-dose
therapy.24
These findings concerning the risks of higher-dose ICS
therapy point toward the potential advantages of adjunctive
therapies for patients with poorly controlled asthma:
for example, adding a LABA, a leukotriene modifier, or
theophylline to medium-dose ICS therapy at step 4 or
adding omalizumab therapy to high-dose ICS therapy plus
a LABA at step 5. Nevertheless, these therapies are also
associated with safety concerns or other disadvantages

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a Clinic Proceedings.

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Managing Asthma in Primary Care

that must be weighed against the clinical benefits. Liver

function must be monitored when patients are taking
zileuton, and the serum concentration of theophylline must
also be monitored.9 The Food and Drug Administration
has issued a black-box warning for omalizumab because
of a small risk of anaphylaxis (corresponding to 0.09%
in postmarketing surveillance studies).25 For this reason,
clinicians who administer omalizumab must be prepared
and equipped to treat anaphylaxis, to observe patients for
an appropriate period of time after each injection, and to
educate patients about the risks of anaphylaxis and the
appropriate treatment if it occurs.26
Additionally, the EPR3 guidelines list malignant neoplasm
as a potential adverse effect of omalizumab because the
pivotal clinical trials found that the incidence of such
neoplasms was higher among patients receiving omalizumab
than among those receiving placebo. Subsequently, the
increased occurrence of malignancies was deemed not to
be due to omalizumab, and an expert panel of oncologists
concluded that only 3 of the reported 25 neoplasms were even
remotely related to the study drug.27,28 As the only approved
biologic therapy for asthma, omalizumab is more expensive
than other controller medications and is administered by
subcutaneous injection in the physicians office. A recent
study showed that the adherence and persistence rates
associated with omalizumab were substantially higher
than those associated with the combination of an ICS and a
LABA, perhaps because the requirement for subcutaneous
injection by a health care professional translates into direct
observation of adherence to therapy.29
For patients with allergic asthma, as indicated by
positive results from a skin test or in vitro RAST testing for
individual aeroallergens, specific allergen immunotherapy
may be an appropriate adjunctive therapy when a clear
relationship exists between asthma symptoms and allergen
exposure. According to the EPR3 guidelines, the evidence
for improved asthma control with immunotherapy is
strongest when patients are affected by single allergens,
especially house dust mites, cat dander, or pollen.9 A patient
with persistent asthma that may be associated with allergy
should probably be referred to an allergist for skin-prick
testing and consideration of immunotherapy, omalizumab
therapy, or both.
When Should the Primary Care Physician Refer a Patient
to an Asthma Specialist?
A referral to a specialist should be considered for any patient
whose asthma is difficult to control, including patients who
do not achieve good control with a combination of an ICS
and a LABA and those who may be considered for therapy
with omalizumab. More specifically, asthma management
guidelines recommend that primary care physicians consider
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Mayo Clin Proc.

referral for patients who have experienced more than 2

oral corticosteroid bursts per year or a recent exacerbation
requiring hospitalization, those who required therapy at step
4 or higher to achieve adequate asthma control, or those for
whom immunotherapy or therapy with omalizumab is being
considered.9
CONCLUSION
Asthma is a chronic condition that often remains uncon
trolled for reasons that may be related to the disease process
itself, the management decisions of clinicians, the patients
perceptions of disease control or self-management behaviors,
the cost of medications, or a combination of all of these
factors. Whatever the reasons for poor control, efforts to
improve it can achieve a notable positive effect on the lives
of patients with asthma. The most recently updated treatment
guidelines from the NAEPP (EPR3) were designed to help
clinicians, including primary care physicians, manage asthma
more effectively, with an increased focus on achieving and
maintaining good asthma control over time.
Proper diagnosis and regular assessment of asthma
control are key components of an effective management
strategy, but improving control depends on recognition by
both the patient and the physician as to what constitutes good
asthma control. To this end, patients with asthma should
be educated not to accept a certain level of symptoms or
activity limitations as an inevitable consequence of asthma.
Both the levels of current impairment and the future risks
(of asthma exacerbations or adverse medication effects)
should be used to inform decisions about appropriate
levels of asthma therapy, and physicians should be aware
of the new medication recommendations included in
the latest NAEPP guidelines. The revised guidelines
emphasize the importance of assessing, achieving, and
continually monitoring asthma control by focusing on the
key domains of impairment and risk. The implementation
of these recommendations by primary care physicians and
other health professionals who are at the forefront of care
is crucial to minimizing the incidence of uncontrolled
asthma at a time when our knowledge of the disease and
the availability of effective medications have fostered an
opportunity for substantial improvement.
The author thanks Marci Mikesell, PhD, for medical writing
assistance in the preparation of the submitted manuscript. Support
for third-party writing assistance was provided by Genentech and
Novartis.

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a Clinic Proceedings.

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