Review Article

Managing Asthma: An Evidence-Based

Approach to Optimizing Inhaled Corticosteroid
Treatment
Leonard Fromer, MD

and emotional well being.2,3 In a 2005 United States study,

Abstract: Asthma is a chronic disease characterized by airway in-
flammation and hyperresponsiveness and is associated with signif-
icant yet avoidable mortality and morbidity resulting in considerable
individual and societal burden. Inhaled corticosteroids are the most
effective class of controller medication available today for treating
persistent asthma and are the evidence-based guideline-recom-
mended first-line treatment for controlling asthma. Although inhaled
corticosteroids have proven to reduce asthma-related exacerbations
that lead to hospitalizations and death, recent studies have shown
that only a small percentage of patients receive appropriate treat-
ment and monitoring for their asthma. Delivering optimal asthma
management requires an understanding and application of basic sci-
ence and evidence-based guidelines in clinical practice. Manage-
ment of a chronic disease in the primary care setting requires over-
coming several barriers due to competing priorities and time
constraints of the physician, as well as the reluctance of patients to
actively participate in their own care. However, evidence has shown
that the patient-centered medical home model can overcome some of
these issues and improve patient outcomes and adherence to therapy.
Key Words: asthma, chronic care model, inflammation, inhaled
corticosteroids, patient-centered medical home model
Overview of Asthma
Asthma is a chronic condition affecting an estimated
22.2 million Americans and 300 million people worldwide,1,2
and it is associated with significant morbidity and mortality.
Poorly controlled asthma can have a significant impact on
patient quality of life, daily activities, personal relationships,
From the Department of Family Medicine, UCLA School of Medicine, Los
Angeles, CA.
Reprint requests to Leonard Fromer, MD, Department of Family Medicine,
UCLA School of Medicine, 15525 Hamner Drive, Los Angeles, CA
90077. Email: MDWelby@aol.com
Dr. Fromer received honoraria as an advisor for Sepracor.
Dr. Fromer has no financial disclosures to declare and no conflicts of interest
to report.
Accepted February 12, 2010.
Copyright © 2010 by The Southern Medical Association
0038-4348/0⫺2000/10300-1038
approximately 78% of adult patients with asthma reported a
limitation in their activities due to their condition over a
weekly period, and 68% had two or more symptomatic days
per week.4 Due to the chronic nature of this disease, asthma
is also associated with substantial direct and indirect health-
care costs. Annual US healthcare costs associated with
asthma are approximately $19.7 billion (in 2005 dollars)
and are largely due to the high number of emergency room
(ER) visits (⬃1.8 million in 2005) and hospital admissions
(⬃500,000 in 2005).2,5,6 Patients without insurance are
more likely to make ER visits than patients with insurance,
potentially indicating suboptimal asthma control in this
population.7 An effective asthma management strategy is
essential to minimize the impact of the disease on patients
and society.
Diagnosis of Asthma
The predominant pathologic feature of asthma is inflam-
mation of large and small airways resulting in episodic air-
Key Points
• The underdiagnosis of asthma demonstrates that there
is a need to integrate asthma guidelines into clinical
practice in order to effect change and ultimately im-
prove patient outcomes.
• Inhaled corticosteroids (ICSs) are currently recom-
mended in national and international guidelines as the
first-line controller medication for adults, adolescents,
and children with persistent asthma.
• Understanding the science behind ICSs may alleviate
physician and patient concerns regarding their adverse
effects, which may be a barrier to the appropriate use
of these medications.
• Fulfilling the need for asthma education, continuity of
care, individualized management programs, and a
strong patient and clinical care-team relationship can
result in better chronic care and asthma treatment
outcomes.

1038 © 2010 Southern Medical Association


way obstruction, characterized by reduced airflow that can
lead to asthma symptoms, which include coughing, wheez-
ing, breathlessness, and chest tightness.1 Intermittent exacer-
bations of these symptoms can also result in variable, revers-
ible airway obstruction, as well as worsened coughing and
wheezing.8
Pulmonary Function
Currently, asthma is underdiagnosed, with many patients
failing to report intermittent respiratory symptoms and, there-
fore, not being adequately treated.1,9 Moreover, due to the
nonspecific symptoms of asthma, many patients may be mis-
diagnosed (with, for example, bronchitis).1 Self-reporting of
symptoms associated with asthma is one method for identi-
fying the disease.1 In patients 5 years of age or older, spiro-
metric lung function measurements (eg, forced expiratory vol-
ume in one second [FEV1], forced vital capacity [FVC], peak
expiratory flow [PEF]), and, in particular, the reversibility of
lung function abnormalities (postbronchodilator FEV1 ⱖ12%
and ⱖ200 mL of prebronchodilator value), are vital tools in
establishing a clear diagnosis.1,10
Causes and Comorbidities
Asthma often coexists with other major health prob-
lems,11 requiring clinicians not only to manage asthma but
also to comanage the other illnesses. Allergic sensitization is
considered the most common precursor to the development of
chronic allergic rhinitis and asthma. Allergic rhinitis is con-
sidered a risk factor for the development of asthma and is one
of the most common comorbidities in asthmatic patients: ap-
proximately 55%12 to 73%13,14 of asthmatic patients have
allergic rhinitis. In some asthma patients, extraesophageal
symptoms (ie, coughing, chest pain, and hoarseness) predom-
inate. It has been suggested that gastroesophageal reflux al-
lows acid into the respiratory tract, leading to inflammation,
irritation, and, consequently, bronchoconstriction.15 In fact,
gastroesophageal reflux disease (GERD) is present in up to
80% of asthmatics and is a potential asthma trigger.15
Issues and Challenges of Diagnosis
Correctly diagnosing asthma is critical for determining
an appropriate treatment regimen.16 There are numerous prob-
lems with diagnosing the disease: for example, the age of the
patient can dramatically influence the method of diagnosis.
The significance of asthma symptoms may be overlooked by
physicians and patients or even misdiagnosed if they are non-
specific (eg, wheezy bronchitis or breathlessness in old age),
since not all respiratory symptoms are specific to asthma.
Diagnosing asthma in children aged five years or younger
is challenging and based largely on clinical judgment and
assessments of family history and physical findings.16 Cough
and episodic wheezing is common in children who do not
have asthma, particularly those aged under three years.17
Southern Medical Journal • Volume 103, Number 10, October 2010
Review Article
Some alternative causes of wheezing that must be excluded
include, but are not limited to, gastroesophageal reflux dis-
ease (GERD), cystic fibrosis, chronic rhinosinusitis, tubercu-
losis, congenital heart disease, and vocal cord dysfunc-
tion.17,18 A trial treatment with short-acting bronchodilators
and inhaled glucocorticosteroids is useful for confirming an
asthma diagnosis in this age group. Children aged 4 –5 years
old often can successfully use a peak expiratory flow (PEF)
meter under adult supervision facilitating diagnosis.19 The
use of spirometry, markers of airway inflammation and other
measures of airway responsiveness, is difficult to measure in
these young patients and requires complex equipment.20 Tests
for atopy, including either in vitro testing for antigen-specific
immunoglobulin E (IgE) antibody or immediate hypersensi-
tivity skin testing are also useful for diagnosing asthma, al-
though skin prick testing in infants is not reliable.1 Lastly, a
chest x-ray can rule out structural abnormalities or chronic
infection in a wheezing child.1
A diagnosis of asthma in children aged over five years
and in adults can typically be confirmed through a careful
history and physical examination coupled with lung function
testing, preferably spirometry or bronchoprovocation (eg,
methacholine challenge), if spirometry values are normal in
the presence of asthma symptoms.1,8,16,21 Diagnosis can be
complicated by coexisting conditions; careful assessment of
both the asthma and any comorbidities is necessary to estab-
lish an appropriate treatment regimen.22
Treatment and Management of Asthma
The goals of asthma treatment are to prevent symptoms,
maintain normal lung function, achieve normal physical ac-
tivity, and prevent exacerbations and hospitalizations.23,24
These goals should be achieved with minimal side effects.
Four broad categories are recommended to be incorporated
into the treatment and management of asthma (Table).16 These
categories are: (1) assess and monitor asthma severity and
asthma control, (2) develop a partnership in care between the
caregiver and the patient, (3) control the environmental fac-
tors (allergens, pollutants, animals and/or certain drugs) and
comorbid conditions that affect asthma symptoms, and (4)
choice of medications.16
Asthma Treatment with Inhaled Corticosteroids
Inhaled corticosteroids are currently recommended in na-
tional and international guidelines as the first-line controller
medication for adults, adolescents and children with persis-
tent asthma.1,8,16 Inhaled corticosteroids (ICSs) bind to glu-
cocorticoid receptors within the lungs to form complexes that
interact with, and consequently inhibit, the activity of the
transcription factors responsible for the synthesis of pro-in-
flammatory agents.25 Currently, there are seven ICSs ap-
proved in the United States for the treatment of asthma: be-
1039
Fromer • Optimizing ICS Therapy in Asthma
Table. Components of asthma care
Assessing and monitoring asthma severity and asthma control
Assess and classify asthma severity by determining the frequency and
degree of symptoms, nighttime awakenings, short-acting ␤2-agonist
use, lung functions, and frequency of exacerbations.
Identify precipitating factors for episodic symptoms (eg, inhalant
allergens, irritants, etc).
Identify comorbid conditions that may affect asthma management.
Assess the patient’s knowledge and skills for self-management.
Instruct and educate patients on their asthma, monitoring asthma
symptoms, and use of inhaler devices.
Assess control after therapy initiation and adjust therapy, if necessary.
During clinical visits, periodically monitor asthma control.
During clinic visits, assess disease control, adherence, medication
device technique, written asthma action plan, and patient concerns
and questions.
During clinic visits, use spirometry to measure lung function.
Education for a partnership in care
Establish strong communication with the patient that is concordant with
the cultural, ethnic, language, literacy, and healthcare needs of the
patient.
Provide patients with written asthma action plans that include
instructions for daily management and an action for worsening
symptoms.
Integrate asthma self-management education into all aspects of asthma
care. Involve all members of healthcare team, including physicians,
nurses, pharmacists, respiratory therapists, and other health care
professionals.
Use a variety of educational strategies to reach people with different
levels of healthcare understanding and learning styles.
Incorporate individualized patient care and tailor treatment according to
the patient’s needs and disease severity.
To encourage patient adherence, choose treatments that are concordant
with the patient’s disease severity, preferences, literacy levels,
ethnic issues, and physical and intellectual capabilities. Review
success of the treatment plan and patient concerns at each visit.
Controlling environmental factors and comorbid conditions that affect
asthma
Evaluate the potential role of allergens, pollutants or irritants on the
asthma symptoms.
Instruct patients who are sensitive to allergens, pollutants, or irritants to
minimize exposure to these factors.
Consider subcutaneous allergen immunotherapy for patients with
persistent asthma when there is a relationship between allergen
exposure and asthma symptoms.
Consider influenza vaccination as asthmatic patients are considered to
be at risk for complications from influenza.
Evaluate the presence of and treat possible comorbid conditions that
may affect asthma symptoms such as gastroesophageal reflux,
allergic bronchopulmonary aspergillus, obesity, obstructive sleep
apnea, rhinitis, sinusitis, stress, and depression.
Medications
Long-term controller medications
Corticosteroids
Cromolyn sodium and nedocromil
Immunomodulators
Leukotriene modifiers
Long-acting ␤2-agonists
Methylxanthines
(Table continues)
1040
Table. Continued
Quick-relief (rescue) medication
Anticholinergics
Short-acting ␤2-agonists
Oral systemic corticosteroids
Patients should be instructed in the use of inhaled medication devices and
the technique should be re-assessed and reviewed at each clinic
visit.
clomethasone dipropionate, budesonide, ciclesonide, flunisolide,
fluticasone propionate, mometasone furoate, and triamcinolone
acetonide.
In clinical studies, ICSs have demonstrated efficacy at
improving lung function and decreasing airway hyperrespon-
siveness, as well as reducing the symptoms, frequency, and
severity of asthma exacerbations.23,25–27 Importantly, regular
use of ICSs reduces the risk of hospitalizations and death
from asthma; a benefit that has not been demonstrated for
alternative asthma therapies.23,27
A stepwise approach is recommended for the treatment
of asthma.16 The age of the patient and the severity of the
asthma determine the type and amount of medication. Ther-
apy is stepped up as necessary to maintain control and stepped
down when possible with the aim of identifying the minimum
of medication required to maintain control. A key component
of this strategy is that once asthma control is achieved, it is
essential to monitor symptoms with follow up clinic visits
because asthma varies over time, making it necessary to ad-
just the therapy periodically. If disease control deteriorates, it
may not reflect inadequate pharmacotherapy but other factors
that may influence treatment outcomes. Therefore, it is also
important to assess the patient’s inhaler technique, treat any
comorbidities, monitor the patient’s environmental control
measures, and determine whether there has been a change in
their environmental exposure. It is also essential to discuss
with the patient the importance of adherence to therapy and
recognition of asthma symptoms. Referral to an asthma spe-
cialist is recommended for consultation or comanagement
of patients who are having difficulty maintaining asthma
control.16
Guidelines recommend using the lowest possible dose of
ICSs that can maintain asthma control.1,16 Combining ICSs
with long-acting ␤2 agonists (LABAs) or other medications
(eg, leukotriene modifiers) can be implemented as mainte-
nance therapy to help control more severe asthma. However,
a LABA should be added to a treatment regimen for patients
over the age of five years only when asthma is not adequately
controlled on low doses of ICSs alone and should not be used
as monotherapy in the treatment of asthma.1,16 This advice
was introduced following evidence suggesting that LABAs
may increase the risk of severe asthma exacerbations and
asthma-related deaths in some patients.28
© 2010 Southern Medical Association

Properties of Inhaled Corticosteroids and Their
Effects on Safety and Efficacy
Although ICSs have a clear and important benefit for
treating asthma, there are local and systemic adverse events
(AEs) associated with their use—particularly when used at
high doses and/or for long periods of time.24,29,30 The safety
profiles of different ICSs vary according to formulation,
method of delivery, subsequent throat and lung deposition,
and pharmacologic characteristics, such as protein binding,
pharmacokinetics, and rate of clearance from the system.31
Potential systemic AEs include a transient reduced growth
rate (in children and adolescents), osteoporosis, suppression
of hypothalamic–pituitary–adrenal-axis function, skin thin-
ning, and cataract formation and have been well stud-
ied.23,24,30 However, local, oropharyngeal, and laryngeal side
effects, including oral candidiasis, dysphonia, and hoarse-
ness, have been less investigated. Nevertheless, these local
side effects can be clinically significant as they affect a pa-
tient’s quality of life, hinder adherence, and can mask symp-
toms of a more serious disease.29,32
In a recent survey, 34% of patients reported having ex-
perienced short-term AEs due to ICSs therapy.33 Concern
regarding these potential risks may preclude asthma patients
from receiving the guideline-recommended treatment, as cli-
nicians may be unwilling to prescribe ICSs at high doses for
long periods, and patients may be unwilling to receive or
adhere to them.34 In fact, in one survey, 21% and 31% of
patients reported switching/discontinuing or skipping medi-
cations, respectively, due to AEs.33 Nonadherence to asthma
medication reduces therapeutic outcomes and increases
healthcare costs due to suboptimally controlled asthma.35
The incidence of oropharyngeal AEs varies between dif-
ferent ICSs and may be associated with the deposition of
active ICSs in the oropharyngeal region.29 Oral deposition
depends on the particle size, as well as delivery device. ICSs
are generally delivered via hydrofluoroalkane (HFA)-me-
tered-dose inhalers (MDI) or dry-powder inhalers (DPIs).
HFA-MDIs are formulated as solutions and deliver smaller-
sized particles than DPIs.36,37 The smaller HFA-MDI parti-
cles (with a mass median aerodynamic diameter of ⬍2 ␮m)
penetrate more efficiently into the smaller airways, increasing
ICSs’ action throughout the lung and reducing the frequency
of oropharyngeal AEs.37–39 The local bioavailability of ICSs
may also be reduced if they are administered as inactive
prodrugs and converted to their pharmacologically active me-
tabolites in the lungs.40,41 This reduces the presence of active
drug in the upper airways, lowering the potential for local
AEs in this region.
Systemic exposure of exogenous corticosteroids can re-
sult in AEs, such as cataract formation and reduced growth
velocity.30 ICSs are bound by serum proteins that inhibit their
function, reducing the activity of the ICSs in other organs (ie,
eyes and bone) and interaction with endocrine systems (ie,
Southern Medical Journal • Volume 103, Number 10, October 2010
Review Article
endogenous cortisol and growth hormone secretion).42 A high
clearance rate and first-pass metabolism also affect systemic
exposure and can influence the occurrence of potential
AEs.41 These molecular and cell biological properties dif-
fer among the ICSs and therefore result in ICSs-specific
systemic characteristics.
The risk-benefit ratio of long-term ICSs treatment has
improved over the last several years, mostly due to the avail-
ability and development of new ICSs molecules administered
as prodrugs that still provide efficacy but have reduced sys-
temic bioavailability.24 A reduced risk for developing AEs
may ease a clinician’s concern regarding the use of ICSs at
high dose and/or for long periods, improve patient adherence,
and allow guideline recommendations for asthma treatment to
be implemented appropriately.
Integrating Knowledge into Clinical
Practice
The Chronic Care Model
Asthma, like all chronic conditions, presents patients and
their families with new challenges that may stand in the way
of achieving successful therapeutic outcomes and quality of
life. Such challenges include dealing with symptoms, disabil-
ity, emotional impact, complex medication regimens, diffi-
cult lifestyle adjustments, and access to helpful medical
care.43 The role of medical care in treating a chronic disease
is to help patients and their families meet and overcome the
challenges of long-term treatment. Most medical practices,
however, are not structured to provide the proactive chronic
care required to give asthma patients the tools they need to
fight the challenges posed by their disease but, rather, lead
to a focus on acute and urgent problem-oriented, reactive
care.43
The Patient-Centered Medical Home Model
The patient-centered medical home model facilitates ap-
propriate chronic care in medical practice through the use of
evidenced-based guidelines in treatment decision making and
by ensuring exceptional patient communication with health
care professionals.44 The latter is facilitated via redesigning
healthcare team workflow such that scheduling, organization
of patient visits, and use of clinical staff are coordinated to
optimally treat, manage, educate, and track asthma patients.
Making these changes requires strong physician leadership
and the training of other clinic staff (nurses, receptionists, and
medical assistants) to perform aspects of care management
not traditionally required of them.45
A key component of the patient-centered medical home
model necessary to improve chronic care is patient-oriented
intervention of an educational and supportive nature, either
through one-on-one or group visits, which aim to increase a
patients’ knowledge, skills, and confidence to create in-
1041
Fromer • Optimizing ICS Therapy in Asthma
formed, activated individuals responsible for their own dis-
ease management.46 This is particularly important in asthma
patients, as they are less likely to be adherent to controller
medications when compared with patients suffering from other
diseases.47 Indeed, adherence to asthma treatment and asthma
morbidity are significantly improved when asthma education is
delivered in combination with pharmacotherapy.48
Improved outcomes for asthma patients and adherence to
medication also correlate with appropriate patient self-mon-
itoring, which can consist of symptom and/or PEF diaries.
Self-monitoring allows for the detection of an asthma exac-
erbation. In one study, ER visits were significantly reduced
by PEF self management.49 Regular patient follow ups, either
face-to-face or over the phone, also correlate with adherence
in asthma patients, as they provide an opportunity to reinforce
and review an educational program as well as monitor asthma
control, possibly by spirometry use, during a follow-up
visit.48 Likewise, an individualized, written, action plan, as
part of an asthma education program, can inform patients of
when and how to modify medications and access the medical
system in response to worsening asthma.48 Access to infor-
mation and care can be better achieved by periodic commu-
nication between the patient and clinical team members. In
one study, an optimal self-management program that pro-
vided patient intervention with information about asthma,
self-monitoring, regularly planned follow-up visits, and writ-
ten action plans resulted in a reduction in the proportion of
subjects reporting hospitalizations and ER visits, unscheduled
doctor visits for asthma, and episodes of nocturnal asthma.48
The patient-centered medical home model empowers asthma
patients to ‘take the driver’s seat’ in the management of their
disease while providing continuity of care services to help
patients overcome the challenges of their disease and adhere
to treatment, thereby preventing exacerbations of symptoms.
Although evidence supports the benefit of the patient-cen-
tered medical home model in asthma, more studies are re-
quired to further validate these findings.
Barriers to Successful Chronic Disease
Management
The chronic care and patient-centered models present the
need for a cultural shift from a healthcare system where phy-
sicians and caregivers have almost complete control and au-
tonomy, to one where patients have more control over their
own care. This is often met with resistance by healthcare
providers, whose education and professional development
have not prepared them for the multifaceted, interconnected
changes in a clinical practice style critical to chronic disease
care.43 Moreover, few physicians believe that they received
any education in communication or teaching skills with re-
gard to patient-focused care.50 In order to overcome this bar-
rier, the medical education curriculum must be adjusted to
1042
include the teaching of a team-based approach to the practice
of medicine and focus on the needs of patients as central to
the care process.
Another barrier is the discrepancy between current pay-
ment policies (Medicare, Medicaid, and private insurers) and
interventions shown to improve chronic disease care, such as
nonvisit methods of interaction, group interactions, and self-
management support.43 Current policies generally do not pro-
vide reimbursement for telephone or other non-face-to-face
patient/provider interactions, group care settings, or patient
education activities, despite the evidence supporting their pos-
itive effect on patient outcomes.43 These issues impede the
progress towards new models of patient care, the result of
which is a lack of infrastructure for the implementation of
workflow redesign in the primary care setting.
Conclusion
Currently available guidelines1,8,16 emphasize asthma
management based on clinical control, rather than disease
severity, and suggest strategies for treating some comorbid
conditions (eg, GERD, stress, depression, allergic broncho-
pulmonary aspergillosis, rhinitis or sinusitis, obesity, and ob-
structive sleep apnea). However, a recent study revealed that
only 13.8% of patients are appropriately monitored and re-
ceive step-up therapy (eg, an increase in inhaled corticoste-
roid [ICSs] dose or add-on of another therapy) if their asthma
is uncontrolled in accordance with guidelines.51 Clearly, there
is a need to integrate asthma guidelines (whether nationally or
locally) into clinical practice in order to effect change and,
ultimately, improve patient outcomes. While the time expen-
diture and effort required on the part of the clinical care team
to translate evidence-based guidelines into real world practice
may not seem worthwhile, studies have shown that approxi-
mately 50% of medical expenditures for asthma are the result
of exacerbations or treatment failure.6
Inhaled corticosteroids are recommended as first-line
controller therapy for all asthma patients and are currently the
most effective treatment for asthma. However, physician and
patient concern regarding systemic and oropharyngeal AEs
may be a barrier to the appropriate use of this medication.
Optimizing the pharmacodynamic and pharmacokinetic char-
acteristics of ICSs may improve their tolerability and safety
profiles and help ease these concerns. Efforts should be made
to find the minimum effective ICSs dose for individual asthma
patients in order to establish a balance between safety and
efficacy, as the benefits of ICSs therapy clearly outweigh the
risks of uncontrolled asthma. Achieving regular, safe, and
correct ICSs use requires knowledge and time from both care-
giver and patient, as lack of adherence can increase exacer-
bation rates and risk of death. Asthma education, continuity
of care, individualized management programs, and a strong
patient and clinical care team relationship can arm patients
with the skills and knowledge needed to meet the challenges
© 2010 Southern Medical Association

of their disease, resulting in better chronic care and asthma
treatment outcomes. The patient-centered medical home
model is a potential means to achieving this end.
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