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

1038 © 2010 Southern Medical Association


Review Article

way obstruction, characterized by reduced airflow that can Some alternative causes of wheezing that must be excluded
lead to asthma symptoms, which include coughing, wheez- include, but are not limited to, gastroesophageal reflux dis-
ing, breathlessness, and chest tightness.1 Intermittent exacer- ease (GERD), cystic fibrosis, chronic rhinosinusitis, tubercu-
bations of these symptoms can also result in variable, revers- losis, congenital heart disease, and vocal cord dysfunc-
ible airway obstruction, as well as worsened coughing and tion.17,18 A trial treatment with short-acting bronchodilators
wheezing.8 and inhaled glucocorticosteroids is useful for confirming an
asthma diagnosis in this age group. Children aged 4 –5 years
Pulmonary Function old often can successfully use a peak expiratory flow (PEF)
Currently, asthma is underdiagnosed, with many patients meter under adult supervision facilitating diagnosis.19 The
failing to report intermittent respiratory symptoms and, there- use of spirometry, markers of airway inflammation and other
fore, not being adequately treated.1,9 Moreover, due to the measures of airway responsiveness, is difficult to measure in
nonspecific symptoms of asthma, many patients may be mis- these young patients and requires complex equipment.20 Tests
diagnosed (with, for example, bronchitis).1 Self-reporting of for atopy, including either in vitro testing for antigen-specific
symptoms associated with asthma is one method for identi- immunoglobulin E (IgE) antibody or immediate hypersensi-
fying the disease.1 In patients 5 years of age or older, spiro- tivity skin testing are also useful for diagnosing asthma, al-
metric lung function measurements (eg, forced expiratory vol- though skin prick testing in infants is not reliable.1 Lastly, a
ume in one second [FEV1], forced vital capacity [FVC], peak chest x-ray can rule out structural abnormalities or chronic
expiratory flow [PEF]), and, in particular, the reversibility of infection in a wheezing child.1
lung function abnormalities (postbronchodilator FEV1 ⱖ12% A diagnosis of asthma in children aged over five years
and ⱖ200 mL of prebronchodilator value), are vital tools in and in adults can typically be confirmed through a careful
establishing a clear diagnosis.1,10 history and physical examination coupled with lung function
testing, preferably spirometry or bronchoprovocation (eg,
Causes and Comorbidities methacholine challenge), if spirometry values are normal in
the presence of asthma symptoms.1,8,16,21 Diagnosis can be
Asthma often coexists with other major health prob- complicated by coexisting conditions; careful assessment of
lems,11 requiring clinicians not only to manage asthma but both the asthma and any comorbidities is necessary to estab-
also to comanage the other illnesses. Allergic sensitization is lish an appropriate treatment regimen.22
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-
Treatment and Management of Asthma
The goals of asthma treatment are to prevent symptoms,
proximately 55%12 to 73%13,14 of asthmatic patients have
maintain normal lung function, achieve normal physical ac-
allergic rhinitis. In some asthma patients, extraesophageal
tivity, and prevent exacerbations and hospitalizations.23,24
symptoms (ie, coughing, chest pain, and hoarseness) predom-
These goals should be achieved with minimal side effects.
inate. It has been suggested that gastroesophageal reflux al-
Four broad categories are recommended to be incorporated
lows acid into the respiratory tract, leading to inflammation,
into the treatment and management of asthma (Table).16 These
irritation, and, consequently, bronchoconstriction.15 In fact,
categories are: (1) assess and monitor asthma severity and
gastroesophageal reflux disease (GERD) is present in up to
asthma control, (2) develop a partnership in care between the
80% of asthmatics and is a potential asthma trigger.15
caregiver and the patient, (3) control the environmental fac-
tors (allergens, pollutants, animals and/or certain drugs) and
Issues and Challenges of Diagnosis comorbid conditions that affect asthma symptoms, and (4)
Correctly diagnosing asthma is critical for determining choice of medications.16
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. Asthma Treatment with Inhaled Corticosteroids
The significance of asthma symptoms may be overlooked by Inhaled corticosteroids are currently recommended in na-
physicians and patients or even misdiagnosed if they are non- tional and international guidelines as the first-line controller
specific (eg, wheezy bronchitis or breathlessness in old age), medication for adults, adolescents and children with persis-
since not all respiratory symptoms are specific to asthma. tent asthma.1,8,16 Inhaled corticosteroids (ICSs) bind to glu-
Diagnosing asthma in children aged five years or younger cocorticoid receptors within the lungs to form complexes that
is challenging and based largely on clinical judgment and interact with, and consequently inhibit, the activity of the
assessments of family history and physical findings.16 Cough transcription factors responsible for the synthesis of pro-in-
and episodic wheezing is common in children who do not flammatory agents.25 Currently, there are seven ICSs ap-
have asthma, particularly those aged under three years.17 proved in the United States for the treatment of asthma: be-

Southern Medical Journal • Volume 103, Number 10, October 2010 1039
Fromer • Optimizing ICS Therapy in Asthma

Table. Components of asthma care Table. Continued


Assessing and monitoring asthma severity and asthma control Quick-relief (rescue) medication
Assess and classify asthma severity by determining the frequency and Anticholinergics
degree of symptoms, nighttime awakenings, short-acting ␤2-agonist Short-acting ␤2-agonists
use, lung functions, and frequency of exacerbations.
Oral systemic corticosteroids
Identify precipitating factors for episodic symptoms (eg, inhalant
allergens, irritants, etc). Patients should be instructed in the use of inhaled medication devices and
the technique should be re-assessed and reviewed at each clinic
Identify comorbid conditions that may affect asthma management. visit.
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. clomethasone dipropionate, budesonide, ciclesonide, flunisolide,
During clinical visits, periodically monitor asthma control. fluticasone propionate, mometasone furoate, and triamcinolone
During clinic visits, assess disease control, adherence, medication acetonide.
device technique, written asthma action plan, and patient concerns In clinical studies, ICSs have demonstrated efficacy at
and questions.
improving lung function and decreasing airway hyperrespon-
During clinic visits, use spirometry to measure lung function.
siveness, as well as reducing the symptoms, frequency, and
Education for a partnership in care
severity of asthma exacerbations.23,25–27 Importantly, regular
Establish strong communication with the patient that is concordant with
the cultural, ethnic, language, literacy, and healthcare needs of the use of ICSs reduces the risk of hospitalizations and death
patient. from asthma; a benefit that has not been demonstrated for
Provide patients with written asthma action plans that include alternative asthma therapies.23,27
instructions for daily management and an action for worsening A stepwise approach is recommended for the treatment
symptoms.
of asthma.16 The age of the patient and the severity of the
Integrate asthma self-management education into all aspects of asthma
care. Involve all members of healthcare team, including physicians, asthma determine the type and amount of medication. Ther-
nurses, pharmacists, respiratory therapists, and other health care apy is stepped up as necessary to maintain control and stepped
professionals. down when possible with the aim of identifying the minimum
Use a variety of educational strategies to reach people with different of medication required to maintain control. A key component
levels of healthcare understanding and learning styles.
of this strategy is that once asthma control is achieved, it is
Incorporate individualized patient care and tailor treatment according to
the patient’s needs and disease severity. essential to monitor symptoms with follow up clinic visits
To encourage patient adherence, choose treatments that are concordant because asthma varies over time, making it necessary to ad-
with the patient’s disease severity, preferences, literacy levels, just the therapy periodically. If disease control deteriorates, it
ethnic issues, and physical and intellectual capabilities. Review
success of the treatment plan and patient concerns at each visit.
may not reflect inadequate pharmacotherapy but other factors
Controlling environmental factors and comorbid conditions that affect
that may influence treatment outcomes. Therefore, it is also
asthma important to assess the patient’s inhaler technique, treat any
Evaluate the potential role of allergens, pollutants or irritants on the comorbidities, monitor the patient’s environmental control
asthma symptoms. measures, and determine whether there has been a change in
Instruct patients who are sensitive to allergens, pollutants, or irritants to their environmental exposure. It is also essential to discuss
minimize exposure to these factors.
with the patient the importance of adherence to therapy and
Consider subcutaneous allergen immunotherapy for patients with
persistent asthma when there is a relationship between allergen
recognition of asthma symptoms. Referral to an asthma spe-
exposure and asthma symptoms. cialist is recommended for consultation or comanagement
Consider influenza vaccination as asthmatic patients are considered to of patients who are having difficulty maintaining asthma
be at risk for complications from influenza. control.16
Evaluate the presence of and treat possible comorbid conditions that Guidelines recommend using the lowest possible dose of
may affect asthma symptoms such as gastroesophageal reflux,
allergic bronchopulmonary aspergillus, obesity, obstructive sleep
ICSs that can maintain asthma control.1,16 Combining ICSs
apnea, rhinitis, sinusitis, stress, and depression. with long-acting ␤2 agonists (LABAs) or other medications
Medications (eg, leukotriene modifiers) can be implemented as mainte-
Long-term controller medications nance therapy to help control more severe asthma. However,
Corticosteroids a LABA should be added to a treatment regimen for patients
Cromolyn sodium and nedocromil over the age of five years only when asthma is not adequately
Immunomodulators controlled on low doses of ICSs alone and should not be used
Leukotriene modifiers as monotherapy in the treatment of asthma.1,16 This advice
Long-acting ␤2-agonists was introduced following evidence suggesting that LABAs
Methylxanthines may increase the risk of severe asthma exacerbations and
(Table continues) asthma-related deaths in some patients.28

1040 © 2010 Southern Medical Association


Review Article

Properties of Inhaled Corticosteroids and Their endogenous cortisol and growth hormone secretion).42 A high
Effects on Safety and Efficacy clearance rate and first-pass metabolism also affect systemic
exposure and can influence the occurrence of potential
Although ICSs have a clear and important benefit for
AEs.41 These molecular and cell biological properties dif-
treating asthma, there are local and systemic adverse events
fer among the ICSs and therefore result in ICSs-specific
(AEs) associated with their use—particularly when used at systemic characteristics.
high doses and/or for long periods of time.24,29,30 The safety The risk-benefit ratio of long-term ICSs treatment has
profiles of different ICSs vary according to formulation, improved over the last several years, mostly due to the avail-
method of delivery, subsequent throat and lung deposition, ability and development of new ICSs molecules administered
and pharmacologic characteristics, such as protein binding, as prodrugs that still provide efficacy but have reduced sys-
pharmacokinetics, and rate of clearance from the system.31 temic bioavailability.24 A reduced risk for developing AEs
Potential systemic AEs include a transient reduced growth may ease a clinician’s concern regarding the use of ICSs at
rate (in children and adolescents), osteoporosis, suppression high dose and/or for long periods, improve patient adherence,
of hypothalamic–pituitary–adrenal-axis function, skin thin- and allow guideline recommendations for asthma treatment to
ning, and cataract formation and have been well stud- be implemented appropriately.
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
Integrating Knowledge into Clinical
side effects can be clinically significant as they affect a pa- Practice
tient’s quality of life, hinder adherence, and can mask symp- The Chronic Care Model
toms of a more serious disease.29,32
Asthma, like all chronic conditions, presents patients and
In a recent survey, 34% of patients reported having ex-
their families with new challenges that may stand in the way
perienced short-term AEs due to ICSs therapy.33 Concern
of achieving successful therapeutic outcomes and quality of
regarding these potential risks may preclude asthma patients
life. Such challenges include dealing with symptoms, disabil-
from receiving the guideline-recommended treatment, as cli-
ity, emotional impact, complex medication regimens, diffi-
nicians may be unwilling to prescribe ICSs at high doses for
cult lifestyle adjustments, and access to helpful medical
long periods, and patients may be unwilling to receive or
care.43 The role of medical care in treating a chronic disease
adhere to them.34 In fact, in one survey, 21% and 31% of
is to help patients and their families meet and overcome the
patients reported switching/discontinuing or skipping medi-
challenges of long-term treatment. Most medical practices,
cations, respectively, due to AEs.33 Nonadherence to asthma
however, are not structured to provide the proactive chronic
medication reduces therapeutic outcomes and increases
care required to give asthma patients the tools they need to
healthcare costs due to suboptimally controlled asthma.35
fight the challenges posed by their disease but, rather, lead
The incidence of oropharyngeal AEs varies between dif-
to a focus on acute and urgent problem-oriented, reactive
ferent ICSs and may be associated with the deposition of
care.43
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- The Patient-Centered Medical Home Model
tered-dose inhalers (MDI) or dry-powder inhalers (DPIs). The patient-centered medical home model facilitates ap-
HFA-MDIs are formulated as solutions and deliver smaller- propriate chronic care in medical practice through the use of
sized particles than DPIs.36,37 The smaller HFA-MDI parti- evidenced-based guidelines in treatment decision making and
cles (with a mass median aerodynamic diameter of ⬍2 ␮m) by ensuring exceptional patient communication with health
penetrate more efficiently into the smaller airways, increasing care professionals.44 The latter is facilitated via redesigning
ICSs’ action throughout the lung and reducing the frequency healthcare team workflow such that scheduling, organization
of oropharyngeal AEs.37–39 The local bioavailability of ICSs of patient visits, and use of clinical staff are coordinated to
may also be reduced if they are administered as inactive optimally treat, manage, educate, and track asthma patients.
prodrugs and converted to their pharmacologically active me- Making these changes requires strong physician leadership
tabolites in the lungs.40,41 This reduces the presence of active and the training of other clinic staff (nurses, receptionists, and
drug in the upper airways, lowering the potential for local medical assistants) to perform aspects of care management
AEs in this region. not traditionally required of them.45
Systemic exposure of exogenous corticosteroids can re- A key component of the patient-centered medical home
sult in AEs, such as cataract formation and reduced growth model necessary to improve chronic care is patient-oriented
velocity.30 ICSs are bound by serum proteins that inhibit their intervention of an educational and supportive nature, either
function, reducing the activity of the ICSs in other organs (ie, through one-on-one or group visits, which aim to increase a
eyes and bone) and interaction with endocrine systems (ie, patients’ knowledge, skills, and confidence to create in-

Southern Medical Journal • Volume 103, Number 10, October 2010 1041
Fromer • Optimizing ICS Therapy in Asthma

formed, activated individuals responsible for their own dis- include the teaching of a team-based approach to the practice
ease management.46 This is particularly important in asthma of medicine and focus on the needs of patients as central to
patients, as they are less likely to be adherent to controller the care process.
medications when compared with patients suffering from other Another barrier is the discrepancy between current pay-
diseases.47 Indeed, adherence to asthma treatment and asthma ment policies (Medicare, Medicaid, and private insurers) and
morbidity are significantly improved when asthma education is interventions shown to improve chronic disease care, such as
delivered in combination with pharmacotherapy.48 nonvisit methods of interaction, group interactions, and self-
Improved outcomes for asthma patients and adherence to management support.43 Current policies generally do not pro-
medication also correlate with appropriate patient self-mon- vide reimbursement for telephone or other non-face-to-face
itoring, which can consist of symptom and/or PEF diaries. patient/provider interactions, group care settings, or patient
education activities, despite the evidence supporting their pos-
Self-monitoring allows for the detection of an asthma exac-
itive effect on patient outcomes.43 These issues impede the
erbation. In one study, ER visits were significantly reduced
progress towards new models of patient care, the result of
by PEF self management.49 Regular patient follow ups, either
which is a lack of infrastructure for the implementation of
face-to-face or over the phone, also correlate with adherence
workflow redesign in the primary care setting.
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 Conclusion
visit.48 Likewise, an individualized, written, action plan, as Currently available guidelines1,8,16 emphasize asthma
part of an asthma education program, can inform patients of management based on clinical control, rather than disease
when and how to modify medications and access the medical severity, and suggest strategies for treating some comorbid
system in response to worsening asthma.48 Access to infor- conditions (eg, GERD, stress, depression, allergic broncho-
mation and care can be better achieved by periodic commu- pulmonary aspergillosis, rhinitis or sinusitis, obesity, and ob-
nication between the patient and clinical team members. In structive sleep apnea). However, a recent study revealed that
one study, an optimal self-management program that pro- only 13.8% of patients are appropriately monitored and re-
vided patient intervention with information about asthma, ceive step-up therapy (eg, an increase in inhaled corticoste-
self-monitoring, regularly planned follow-up visits, and writ- roid [ICSs] dose or add-on of another therapy) if their asthma
ten action plans resulted in a reduction in the proportion of is uncontrolled in accordance with guidelines.51 Clearly, there
subjects reporting hospitalizations and ER visits, unscheduled is a need to integrate asthma guidelines (whether nationally or
doctor visits for asthma, and episodes of nocturnal asthma.48 locally) into clinical practice in order to effect change and,
The patient-centered medical home model empowers asthma ultimately, improve patient outcomes. While the time expen-
patients to ‘take the driver’s seat’ in the management of their diture and effort required on the part of the clinical care team
disease while providing continuity of care services to help to translate evidence-based guidelines into real world practice
patients overcome the challenges of their disease and adhere may not seem worthwhile, studies have shown that approxi-
to treatment, thereby preventing exacerbations of symptoms. mately 50% of medical expenditures for asthma are the result
Although evidence supports the benefit of the patient-cen- of exacerbations or treatment failure.6
tered medical home model in asthma, more studies are re- Inhaled corticosteroids are recommended as first-line
quired to further validate these findings. 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
Barriers to Successful Chronic Disease may be a barrier to the appropriate use of this medication.
Management Optimizing the pharmacodynamic and pharmacokinetic char-
The chronic care and patient-centered models present the acteristics of ICSs may improve their tolerability and safety
need for a cultural shift from a healthcare system where phy- profiles and help ease these concerns. Efforts should be made
sicians and caregivers have almost complete control and au- to find the minimum effective ICSs dose for individual asthma
tonomy, to one where patients have more control over their patients in order to establish a balance between safety and
own care. This is often met with resistance by healthcare efficacy, as the benefits of ICSs therapy clearly outweigh the
providers, whose education and professional development risks of uncontrolled asthma. Achieving regular, safe, and
have not prepared them for the multifaceted, interconnected correct ICSs use requires knowledge and time from both care-
changes in a clinical practice style critical to chronic disease giver and patient, as lack of adherence can increase exacer-
care.43 Moreover, few physicians believe that they received bation rates and risk of death. Asthma education, continuity
any education in communication or teaching skills with re- of care, individualized management programs, and a strong
gard to patient-focused care.50 In order to overcome this bar- patient and clinical care team relationship can arm patients
rier, the medical education curriculum must be adjusted to with the skills and knowledge needed to meet the challenges

1042 © 2010 Southern Medical Association


Review Article

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