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Evidence Based Asthma
Diagnosis and Management
2007 EPR CPG Update
Henry A. Wojtczak, M.D.
[email protected]
Learning Objectives
• Understand how to diagnosis and assess asthma
• Recognize the goals of asthma therapy
• Be able to recommend optimal treatment strategies
for patients with asthma of varying severity
• Determine the optimal controller medications for
patients with persistent asthma
• Understand the proposed changes to the NHLBI
Asthma guideline for 2007
• Identify the vital role the pharmacist plays in asthma
disease management
“The Literature” on Asthma, as Indexed
in PubMed (Last 5 Years)
• 22,135 citations under “asthma”
• 3301 English-language articles on search
terms “asthma” & “management”
• 9 indexed journals with “asthma” in their
name
• 80 clinical practice guidelines
NAEPP Expert
Panel Report 2
• Issued, 1997
NIH Publication #97-4051
• Updated in Selected
Areas, 2002
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
Burden of Disease
General
• Over 300 million asthmatics worldwide1
• 20.5 million Americans have Asthma2
– Approximately 6.5 million children are affected2
• 10.6 million individuals experienced an asthmatic episode
during the previous 12 months
• Nearly 500,000 hospitalizations for asthma anualaly in the
US
1.
2.
Allergy 2004 Global Burden of Asthma: 59; 469-478
National Center for Health Statistics. Raw Data from the National Health
Interview Survey, US, (2005)
Burden of Disease
Death Rate, 1979 to 1997
1.8
1.6
Deaths
per
100,000
Population
Female
Male + Female
Male
1.4
1.2
1
0.8
'79 '80 '81 '82 '83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97
Year
National Center for Health Statistics. Raw Data from the National Health Interview Survey, US,
1997-1998. (Analysis by the American Lung Association Best Practices Division, Using SPSS and
SUDAAN software)
Definition, Pathophysiology,
and Pathogenesis
• Asthma as a chronic inflammatory disorder of the
airways
• Persistent structural changes in some patients
• Increasing importance of gene-by-environment
interactions
• Strongest identifiable predisposing factor: atopy
• Viral infections as important precipitants of
exacerbations and development of asthma
Current Understanding of
Pathogenesis
• Development of asthma cannot be prevented
in susceptible individuals
• Daily long-term control medication does not
alter the underlying course of the disease
Clinical Presentation
• May present as any combination of the following
symptoms: episodic wheezing, shortness of breath,
or coughing paroxysms
• Patients will sometimes relate a history of frequent
“bronchitis” or “reactive airway disease”.
• Often related to specific triggers (cold air,
exercise,viral upper respiratory tract infections)
• Often have a personal or family history of atopic
disorders (allergic rhinitis, asthma,eczema)
Diagnosing Asthma
• Asthma is, ultimately, a clinical diagnosis.
– Historical and objective data must be
combined to arrive at the diagnosis.
• History
– Cough, recurrent wheeze, SOB.
• Note: Many patients may not note wheezing. Cough
may be the primary presentation.
– Symptoms worsen with triggers such as
allergen exposure, exercise, pollutants.
– Symptoms occur or worsen at night, resulting
in awakening.
Diagnosing Asthma
• Physical exam
– wheezing is not always asthma
– asthma patients do not always wheeze, even
during an exacerbation
– Improvement in the physical exam usually
noted after bronchodilator treatment
Diagnosis
• Objective lung studies: In patients > 4
years old, spirometry is used to:
– Document airflow changes consistent with an
obstructive lung disease such as asthma
– Document clinically suspected reversible*
airways obstruction in patients.
– Some young patients (4-8 yo) will have
difficulty producing reliable spirometry.
*Reversible means that a bronchodilator such as albuterol
decreases or “reverses” the airflow obstruction. (FEV1 or
FVC increases 12%; see below)
Diagnosis
• Documenting reversible airflow obstruction is the
most accurate method to diagnose asthma
– Since asthma is an episodic disease, the lack of
reversibility during a healthy period does not rule out
asthma
• There are 3 ways to document reversible
obstruction.
– (1) Spirometry; pre- and post- inhaled bronchodilator
therapy (eg, albuterol)
– (2) Spirometry before and after a course of systemic or
inhaled steroids.
– (3) Bronchoprovocation studies
Spirometry Diagnosis
• Classically, see a low FEV1 (amount of air expired in one
second with maximal effort) with a decreased FEV1 / FVC
ratio in an asthmatic with active airflow limitation.
• To help confirm asthma, after a bronchodilator or a course
of steroids, expect to see:
– Increase in FVC, FEV1, or FEV1/FVC ratio of 12% from baseline;
or an increase in FEF 25-75 of 30% from baseline
– In adults, an absolute increase of 200ml in FVC and FEV1 should also
be seen
Failure to see 12% increase or greater does not mean
asthma is excluded.
Normal ( red) vs. Asthma (black) Flow Volume Loop
PFT Sheet
Precipitating / Sustaining Factors
for Asthma
•
•
•
•
•
•
•
•
Allergen exposure
Allergic Rhinitis
Exercise
Viral URI’s
Rhinosinusitis
GERD
Cigarette smoke
Environmental exposures
(eg, pollution, fumes)
Viral Respiratory Infections
• The vast majority (~80%) of acute asthma
exacerbations are secondary to viruses
• Most common agent is rhinovirus
• Mechanism is poorly understood
• Most plausible is that existing airway
inflammation is up-regulated
• Frequent hand washing and routine influenza
vaccination can prevent viral-induced asthma
exacerbations
Allergen Exposure/Allergic Rhinitis
• Estimated that 50% or so of asthmatics are atopic.
• In these individuals, allergens are believed to be a major
driving factor in chronic inflammation.
• Most significant indoor allergens are dust mite, cat and
cockroach.
• Outdoor allergens can also prompt airway inflammation.
• Allergy skin testing or RAST can help identify which
allergens are important in individual patients
– Allergen avoidance may result in disease improvement.
• Control of the atopic response with long acting
antihistamines, inhaled nasal steroids or leukotriene
inhibitors can help decrease asthma symptoms that are
allergen related
Exercise-Induced Bronchospasm
• Probably a subset of asthma, rather than a distinct clinical
entity.
• Classically, see worst symptoms and airway obstruction 5
to 10 minutes after exercise.
• Those with symptoms exclusively during exercise are
probably mild asthmatics who only get symptoms at the
extremes of exertion.
– Possibly due to cool, dry air inspiration that results in
drying/irritation of bronchial mucosa.
– Typically pre-treatment with short acting beta agonist prior to
exercise limits the symptoms from exercise induced asthma, as does
exercise conditioning.
– Consider alternative diagnoses such as vocal cord dysfunction
especially if symptoms not improved by bronchodilator pretreatment
Gastroesophageal Reflux
(GER) and Asthma
• GER has been proposed by many authors as a chronic and
acute driving factor for asthma, likely via a vagal reflex.
• In studies, perfusion of acid into the esophagus leads to an
increase in cough response and increased airways
hyperresponsiveness.
• Studies show medical treatment with a proton pump
inhibitors can improve asthma symptom control, but not
objective lung studies (eg. PEF, FEV1).
– studies suggest up to 70% improvement in symptoms.
• Fundoplication may provide even better results than
medical management.
Rhinosinusitis and Asthma
• National Heart Lung and Blood Institute (NHLBI)
Asthma CPG recognizes that chronic
rhinosinusitis can contribute to asthmatic
inflammation and poor disease control.
– 50-80% of asthmatics have chronic rhinitis
• By an unknown mechanism (neural?),
inflammation of the nose and sinuses appears to
drive or worsen asthma in some individuals.
• Curing the sinus/nasal disease often markedly
improves the asthma (ie: inhaled nasal
corticosteroid, sinus polyp surgery, long term
antihistamines) .
Asthma: Making the Diagnosis
• Differences from 1997 & 2002 guidelines
– Emphasis on spirometry
• Preference over peak flow for diagnosis
• Inclusion of FEV6 as well as FVC
• Recommended in children > age 4
Asthma: Making the Diagnosis
• Differences from 1997 & 2002 guidelines
– Consideration of alternative diagnoses
•
•
•
•
•
Vocal cord dysfunction
Cough variant asthma
Gastroesophageal reflux disease
Obstructive sleep apnea
Allergic bronchopulmonary aspergillosis
NHLBI
National Asthma Education
and Prevention Program
Expert Panel Guidelines for the
Diagnosis and Management of
Asthma (EPR-3)
Due Summer 2007
(Draft for Comment by Stakeholding Groups, January 2007)
Key Differences From 1997 Guideline
• The critical role of inflammation has been further
substantiated, but evidence is emerging for
considerable variability in the pattern of
inflammation, thus indicating phenotypic
differences that may influence treatment
responses.
• Gene-by-environmental interactions are important
to the development and expression of asthma. Of
the environmental factors, allergic reactions
remain important. Evidence also suggests a key
and expanding role for viral respiratory infections
in these processes.
Key Differences From 1997 Guideline
• The onset of asthma for most patients begins early
in life with the pattern of disease persistence
determined by early, recognizable risk factors
including atopic disease, recurrent wheezing, and
a parental history of asthma.
• Current asthma treatment with anti-inflammatory
therapy does not appear to prevent disease
progression
Assessment
• The key elements of assessment and
monitoring are refined to include the separate,
but related, concepts of
– Severity
– Control
– Responsiveness to treatment
Severity Classification
• Classifying severity is emphasized for
initiating therapy; assessing control is
emphasized for monitoring and adjusting
therapy.
• Asthma severity and control are defined in
terms of two domains
– Impairment
– Risk
Severity Classification
• Severity classification is defined in terms of two
domains—impairment and risk—to emphasize the
need to consider separately asthma’s effects on
– Quality of life and functional capacity on an ongoing basis
(i.e., in the present)
– The risks that asthma presents for adverse events in the
future, such as exacerbations and progressive loss of
pulmonary function.
• These domains of asthma may respond differentially
to treatment.
Severity Classification
• New parameters for pulmonary function
measures—FEV1/FVC—have been added to
classify severity for children.
• The severity classification for chronic asthma
changed the category of mild intermittent to
intermittent in order to emphasize that even
patients who have intermittent asthma can have
severe exacerbations.
Diagnosis
• Information on vocal cord dysfunction (VCD) and
cough variant asthma as an alternative diagnosis
has been added.
• Reference has been added to updated information
in another component on comorbid conditions that
may complicate diagnosis and treatment of asthma
(e.g., allergic bronchopulmonary aspergillosis
(ABPA), obstructive sleep apnea (OSA), and
GERD).
Control
• Evidence strengthens recommendations that reducing
exposure to inhalant indoor allergens can improve asthma
control and notes that a multifaceted approach is required;
single steps to reduce exposure are generally ineffective.
• Formaldehyde and volatile organic compounds (VOCs)
have been implicated as potential risk factors for asthma
and wheezing.
• Evidence shows that influenza vaccine, while having other
benefits, does not appear to reduce either the frequency or
severity of asthma exacerbations during the influenza
season.
• The section has been expanded to include discussion of
ABPA, obesity, OSA, and stress as chronic comorbid
conditions that may interfere with asthma management, in
addition to rhinitis, sinusitis, and gastroesophageal reflux.
Patient Education
• Emphasis on the many potential points of care and sites
available in which to provide asthma education, including
review of new evidence regarding the efficacy of asthma
self management education outside the usual office setting.
• Greater emphasis on the two aspects of the asthma action
plan—(1) daily management, and (2) early recognition of
and actions for handling exacerbations.
– Use of the terminology “asthma action plan” encompasses both
aspects. This change addresses confusion over the previous
guideline’s use of different terms for asthma management plans.
One term is now used.
• New sections on the impact of cultural and ethnic factors
and health literacy that affect delivery of asthma selfmanagement education.
Provider Education
• New section with review of system-based
interventions to improve the quality of asthma
care, to support clinical decision-making, and to
enhance clinical information systems
• Review of tested programs that use effective
strategies to provide clinician education in asthma
care, e.g., multidimensional approaches,
interactive formats, and practice-based case
studies
Medications
•
•
•
•
•
•
Information about asthma medications has been updated based on review of
evidence published since 1997.
This updated report (EPR—3) continues to emphasize that the most effective
medications for long-term therapy are those shown to have anti-inflammatory
effects.
New medications—immunomodulators—are available for long-term control
and prevention of symptoms.
New data on the safety of LABAs are discussed, and the position of LABA in
therapy has been revised (see text). The most significant difference is that for
youths ≥12 years of age and adults whose asthma is not controlled on low-dose
ICS, the option of increasing the dose of ICS should be given equal weight to
the option of adding LABA to low-dose ICS.
The estimated clinical comparability of different ICS preparations has been
updated.
The significant role of ICSs in asthma therapy continues to be supported.
Medications
• Recommendations for managing asthma in
children 0–4 and 5–11 years of age are presented
separately from recommendations for managing
asthma in youths >12 years of age and adults.
• Treatment decisions for initiating long-termcontrol therapy are based on classifying severity
(considering both the impairment and risk
domains) and selecting a corresponding step for
treatment.
• Recommendations on when to initiate therapy in
children 0–4 years of age have been revised
Medications
• Treatment decisions for adjusting therapy and
maintaining control are based on assessing the
level of asthma control (considering separately
asthma’s effects on quality of life and functional
capacity on an ongoing basis (i.e., in the present)
and the risks it presents for adverse events in the
future, such as exacerbations and progressive
reduction in lung growth or lung function.
Medications
•
•
Stepwise approach to managing asthma has been expanded to include six steps
of care to simplify the actions within each step. For example, previous
guidelines had several progressive actions within step 3, whereas the current
guidelines separate the actions into different steps.
Treatment options within the steps have been revised, especially:
– For patients not well controlled on low-dose inhaled corticosteroid (ICS),
increasing the dose of ICSs to medium dose is recommended before adding
adjunctive therapy in the 0–4 years age group; for other age groups (children 5–11
years of age and youths ≥12 years of age and adults), increasing the dose of ICS to
medium dose or adding adjunctive therapy to a low dose of ICS are considered as
equal options.
– Evidence for the selection of adjunctive therapy is limited in children under 12
years of age; recommendations vary according to the assessment of impairment or
risk.
– Steps 5–6 for youths ≥12 years of age and adults include consideration of
omalizumab.
•
Managing special situations has been expanded to include racial and ethnic
disparities.
Exacerbation Management
• For the assessment of exacerbations, the current update (EPR—3):
simplifies classification of severity of asthma exacerbations.
• Reinstates the 1991 cut points of forced expiratory volume in 1 second
(FEV1) or peak expiratory flow (PEF) to indicate the goal for
discharge from urgent care (≥70 percent predicted FEV1 or PEF);
patients for whom response to therapy is incomplete and who usually
require continued treatment in the ED (40–69 percent predicted); and
the exacerbation severity level where adjunct therapies may be
considered (<40 percent predicted). These cut points differ from those
used to determine long-term asthma control and treatments, thus
underscoring the distinction between acute and chronic asthma
management.
• Acknowledges the limited value of pulmonary function measures in
very severe exacerbations.
Exacerbation Management
• For the treatment of exacerbations, the current update:
• For acute exacerbations, adds levalbuterol as a SABA treatment.
• For home management of exacerbations, no longer recommends
doubling the dose of ICSs.
• For pre-hospital management (e.g., emergency transport), encourages
standing orders for albuterol and—for prolonged transport—repeated
treatments and protocols to allow consideration of ipratropium and oral
corticosteroids.
• For ED management, reduces dose and frequency of administration of
oral corticosteroids in severe exacerbations; adds consideration of
magnesium sulfate or heliox for severe exacerbations; and adds
consideration of initiating an ICS upon discharge.
• For hospital management, no longer recommends ipratropium bromide
Preview of the New Guidelines:
Important Disclaimer
• The January 2007 EPR-3 draft is not yet an official
document, and is not for dissemination.
• I will point out any areas that appear to be major
departures from EPR-2 or that differ significantly
from other current guidelines.
• A number of changes will likely be made before
official release.
The Revised Assessment of
Asthma Severity (2007)
• The most recent NHLBI Asthma CPG emphasizes
– Evaluation of the asthma patient’s severity at time of
diagnosis and
– Control of asthma symptoms after initiation of therapy.
• Every asthma evaluation should consider:
– The patient’s current impairment and
– Risk for disease progression.
Initial Asthma Severity
Classification
• Current NHLBI Asthma CPG classifies newly
diagnosed asthmatics into 4 groups based on
severity
• Classification is important for physician
communication and so appropriate initial therapy
can be used based on published guidelines
• NHLBI (National Heart Lung and Blood
Institute)/NIH guidelines for the diagnosis and
management of asthma available online:
www.nhlbi.nih.gov/guidelines/asthma
Pediatric Asthma Deaths:
Mild Patients Are Also at Risk
40
35
30
Patient
Deaths
(%)
25
20
15
10
5
0
Severe
Moderate
Mild
Patient Assessment
Findings from a cohort study reviewing all pediatric asthma-related deaths (n=51)
in the Australian state of Victoria from 1986 to 1989.
Robertson et al. Pediatr Pulmonol. 1992;13:95-100.
Classification of Asthma Severity:
Clinical Features Before Treatment
Classification of Asthma Severity:
Clinical Features Before Treatment
Classification of Asthma Severity:
Clinical Features Before Treatment
The 4 Components of
Asthma Management
• Assessment and monitoring, using objective
measures and structured evaluation of specific
aspects
• Control of environmental factors and
comorbidities
• Education for a partnership in asthma care
• Pharmacologic therapy
Asthma: Initial Assessment
• Identify precipitating factors
• Identify comorbidities
• Classify asthma severity
– Impairment domain
– Risk domain
Assessing Control: When to
Intensify or Reduce Therapy
• The following NHLBI Asthma CPG guides
assessment at follow-up and recommends
varying intensities of therapy, based on the
current control of asthma impairment and
risk.
Periodic Assessment: Are the Goals
for Asthma Control Being Met?
• Reduce impairment
–
–
–
–
–
Symptoms: daytime; nocturnal; on exertion
Use of SABA (goal: < 2x/week)
Activity levels (exercise/work/school)
Pulmonary function (normal or near normal)
Patient and family expectations
Periodic Assessment: Are the Goals
for Asthma Control Being Met?
• Reduce risk
– Prevent exacerbations; minimize need for
emergency room visits and/or admissions
– Prevent progressive loss of lung function
– Provide optimal pharmacotherapy with minimal
adverse effects
Periodic Assessment: Components
of Evaluation
• Signs and symptoms of asthma
• Pulmonary function
• Quality of life & functional status
• History of exacerbations
• Review pharmacotherapy
• Patient-provider communication and
satisfaction
When Pulmonary Function Should
Be Assessed with Spirometry
• Initial assessment
• After treatment is initiated and symptoms
and PEF have stabilized
• During periods of loss of asthma control
• At least every 1-2 years
Managing Asthma Long-Term
• Written action plan
– Signs, symptoms, and/or PEF
– Especially important in moderate- to
severe persistent asthma
• Self-monitoring is key
Peak Flow & Symptom-Based
Home Action Plan
Respiratory Rate & SymptomBased Home Action Plan
Which Patients Should Be Monitored
with Peak Flow Measurements?
• Moderate- to severe persistent asthma
• History of severe exacerbations
• Poorly perceived symptoms of
worsening airflow obstruction
GINA Pocket Guide for Asthma
Management and Prevention*
http://www.ginasthma.com/
Stepwise Approach to Therapy:
Maintaining Control (0-4 yo)
Stepwise Approach to Therapy:
Maintaining Control (5-11 yo)
Stepwise Approach to Therapy:
Maintaining Control (12+ yo)
Patient Assessment and Monitoring:
Differences from the Old Guidelines
• Emphasis on distinction between asthma severity
and asthma control
• Emphasis on periodic assessment of control
• Attention to domains of impairment and risk
• Peak flow vs symptom monitoring
– Less emphasis on diurnal PEF
• Importance of specific monitoring plan
Pharmacologic
Therapy
• Long-Term Control Medications
• Quick-Relief Medications
Pharmacotherapy
(Long-Term Controllers)
•
•
•
•
•
Inhaled steroids*
Long-acting beta agonists*
Leukotriene Receptor Agents (LTRA’s)
Theophylline
Omalizumab (Xolair)
* If prescribing controller medications via MDI, the patient
should use a Valved Holding Chamber (e.g. Aerochamber)
Low-dose ICS and the Prevention
of Death from Asthma in Canada
2.5
2.0
Rate Ratio
for Death
from Asthma
1.5
1.0
0.5
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12
Number of Canisters of ICS per Year
Suissa et al. N Engl J Med. 2000;343:332-336.
Benefits of ICS
•
•
•
•
•
•
Reduces symptom severity
Improves pulmonary function
Reduces bronchial hyper-reactivity
Reduces rescue inhaler use
Reduces exacerbations and hospitalizations
May prevent airway remodeling (lung scarring)
Guidelines for the Diagnosis and Management of Asthma. 1997. NIH Publication
No. 97-4051.
Quick-Relief Medications
• Anticholinergics
• Short-acting beta agonists
(SABAs)
• Systemic corticosteroids
Short-Acting Beta Agonists
(SABA) in Asthma
• Most effective agents available for acute
bronchospasm
• Use of > 1 canister/month indicates
inadequate asthma control
• Regularly-scheduled, daily, chronic use of
SABAs is NOT recommended
Relative Risk of Hospitalization
in the United States
2-agonists
8
Total
Age 0-17
Age 18-44
Age 45+
7
6
Relative 5
Risk 4
ICS
3
Total
Age 0-17
Age 18-44
Age 45+
2
1
0
None 0-1
1-2
2-3
3-5
5-8
8+
Prescriptions per person-year
Donahue et al. JAMA. 1997;277:887-891.
Pharmacologic Therapy: Differences
from the Old Guidelines
• Emphasis on agents with anti-inflammatory
properties for long-term control
• Revision of position of LABAs in long-term control
scheme: more priority for increased doses of ICS as
option
• Addition of immunomodulators for long-term control
SMART (Salmeterol Multicenter
Asthma Research Trial) Study*
• Randomized, placebo-controlled, double-blind study
of adding salmeterol to “usual therapy” for asthma
(26,355 patients)
• Terminated early because of increases in respiratoryand asthma-related deaths and life-threatening
experiences in salmeterol group
• These adverse events were more frequent in AfricanAmerican patients, especially if not also taking
inhaled corticosteroids
*Nelson HS et al, Chest 2006;129:15-26
SMART (Salmeterol Multicenter
Asthma Research Trial) Study*
• African-American patients in study
– Comprised 18% of total study patients
– Had lower baseline lung function
– Utilized more urgent health care services
– Fewer of them were using ICS
• ? worse asthma and worse management
• FDA required “Black Box” warning on all LABAs
as result of these findings
*Nelson HS et al, Chest 2006;129:15-26
If Persistent Asthma Not Adequately
Controlled with Low-Dose ICS*
• GINA: Add LABA (ie, use combination rx)
rather than ICS dose
• New NAEPP Guideline (1/07 draft): ICS
dose alone is acceptable alternative in light of
SMART Study findings
*Moore WC, Peters SP. AJRCCM 2007;175:649-654
Anticholinergics in Asthma
• In the emergency treatment of acute severe
asthma, ipratropium has beneficial effects
when added to SABAs.*
• There is no evidence for benefit from either
ipratropium or tiotropium in stable asthma.
• Neither drug is FDA approved for use in
asthma.
*Meta-analysis: Rodrigo GJ et al, Thorax 2005;60:740-746
“Step Therapy” Age 0-4 years
“Step Therapy” Age 5-11 years
“Step Therapy” Age 12 years +
Asthma Therapy
• Goals of asthma therapy– Prevent symptoms that limit activity and/or
result in missed school/work days.
– Avoid hospitalizations/ER visits.
– Avoid asthma deaths (3,000 - 5,000/year).
– Prevent “unchecked” inflammation (poorly
perceived PFT abnormalities) that can lead to
airway remodeling and irreversible damage.
Asthma Therapy Goals
• Obvious triggers of airway inflammation
should be treated and/or avoided if possible.
– Allergen avoidance may be useful adjunct to
meds (for identified indoor allergens).
• Treat allergic rhinitis, sinusitis, GER.
• Full physical activity should be encouraged.
Intermittent
• NHLBI Asthma CPG states that patients may be
treated with prn bronchodilators alone as long as
all of the following are true:
– Symptoms continue to occur two or less times weekly
– Nighttime symptoms (awakenings) are occurring less
than twice monthly
– Rescue BD use < 2/ week
– Normal Spirometry
– No interference with normal activity
– < 1 exacerbation yearly
Mild Persistent
• These are patients with symptoms more than
twice weekly (but not daily) who have normal
baseline spirometry.
• Require Long-Term Controller (ICS)!!!
• The vast majority of experts and clinicians use
inhaled steroids as the treatment of choice for
first line therapy in persistent asthma.
– If one is considering not using inhaled steroids as
the first line agent, there should be a compelling
reason for that decision.
Mild Persistent
• Using leukotriene modifiers (eg, Accolate,
Singulair) mono-therapy as a LTC is discouraged.
• Low dose inhaled steroids (e.g., fluticiasone
(Flovent) 44 mcg/puff, 2 puffs BID) are usually
sufficient in this group.
• Patients should be instructed to rinse mouth after
use to avoid thrush and dysphonia.
• If not controlled with the above, the patient is
most likely a moderate persistent asthmatic.
Moderate Persistent
• These are patients with daily symptoms, or
baseline FEV1 60-80% predicted.
• Three treatment choices
– Going from low to medium dose ICS (eg, fluticasone
110 mcg/puff, 2 puffs bid) (preferred) OR
– Add a long-acting bronchodilator (eg, salmeterol) to
low-dose ICS
– Less attractive alternative:
– Add an anti-leukotriene agent (eg, montelukast) to lowdose ICS
Moderate Persistent
• A change in the recent NHLBI Asthma CPG
:
– For Moderate Persistent asthma, increasing ICS
from low-dose to medium dose is preferred
over adding LABA or LTRA.
Meta-analysis
Clinic FEV1 at 6 Months
Ind
Greening
Woolcock
Kelsen
Murray
Kalberg
Condemi
van Noord (LD)
van Noord (HD)
Vermetten
Fixed effects
Random effects
-0.50
-0.25
0.00
0.25
Treatment difference (L)
Favors
increasing ICS
Adapted from Shrewsbury et al. Br Med J. 2000;320:1368-1373.
Favors adding
salmeterol
0.50
Meta-analysis
Mean Percentage of Symptom-Free
Days at 6 Months
Ind
Greening
Woolcock
Kelsen
Murray
Kalberg
Condemi
van Noord (LD)
van Noord (HD)
Vermetten
Fixed effects
Random effects
-40
-30
-20
-10
0
10
20
Treatment difference (%)
Favors
increasing ICS
Adapted from Shrewsbury et al. Br Med J. 2000;320:1368-1373.
30
Favors adding
salmeterol
40
FP/SAL DISKUS 100/50 vs FP 100 mcg +
Montelukast 10 mg Study Design
FP/SP DISKUS 100/50 BID (n=222)
Run-in
FP 100 mcg
inhalation powder
BID
FP 100 mcg BID + MON 10 mg QHS (n=225)
3 weeks
12 weeks
Patients:
•15 years of age
• Baseline FEV1 50%-80% of predicted
• Symptomatic on ICS
MON, montelukast
Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095.
FP/SAL DISKUS 100/50 vs. LTRA: AM PEFR
FP 100 mcg BID + MON 10 mg QD
FP/SAL DISKUS 100/50 BID
35
Mean Change from Baseline
in AM PEF (L/min)
30
*
25
20
15
10
5
0
Baseline
7
14
21
28
35
42
49
56
63
70
Day
Baseline AM PEF: FP/Sal DISKUS 100/50 = 398 L/min; FP + MON = 392 L/min.
* P0.001 vs FP + MON at Endpoint.
Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095.
77
84 Endpoint
(last evaluable
measurement)
FP/SAL Discus vs. MON 10:
Rescue Albuterol Use
Week
Mean Change from Baseline in
Rescue Albuterol Use (puffs/day)
Baseline
0
-0.2
-0.4
-0.6
-0.8
-1
-1.2
-1.4
-1.6
-1.8
-2
1
2
3
4
5
6
7
8
9
10
11
12 Endpoint
FP/SP DISKUS 100/50 BID
FP 100 mcg BID + MON 10 mg QD
*
Baseline albuterol use (puffs/day): ADVAIR DISKUS 100/50 = 3.77; FP + MON = 3.73.
* P=0.004 vs FP + MON at Endpoint.
No significant difference between treatments was observed for the Overall Daytime Symptom Score.
Statistical significance was not achieved in the replicate study for median percentage of rescue-free nights.
Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095.
FP/SAL DISKUS 100/50 vs. FP/MON 10 mg
FEV1 Changes
Mean % Change from
Baseline in AM Postdose FEV1
16
*
14
I
I
I
I
I
12
10
8
I
*
*
*
*
I
I
I
I
6
4
FP/SAL DISKUS 100/50 BID
2
FP 100 mcg BID + MON 10 mg QD
0
Baseline
1
4
8
12
Week
Baseline FEV1: ADVAIR DISKUS 100/50 = 2.38 L; FP + MON = 2.39 L.
*P<0.001 vs FP + MON.
Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095.
Endpoint
Long-acting Beta2-Agonists
(LABA)
• If needed, these agents should only be used in conjunction
with an inhaled corticosteroid (they act synergistically).
• Therapy with LABA alone may just be bronchodilating
without any effect on the underlying inflammation.
• This can result in undesirable clinical outcomes so this
agent should NEVER be used alone for asthma.
• Recent studies have called into question the long-term
safety of salmeterol. Consideration for its use should be
limited to those patients uncontrolled on inhaled steroids
alone.
Severe Persistent
• These are patients with continual symptoms,
baseline FEV1 under 60%, frequent nighttime
awakenings, multiple hospitalizations and/or
intubations
• Need high dose ICS, LABA, and possibly LTRA
as well.
• Theophylline, Omalizumab (anti-IgE therapy) or
oral steroids may be required to fully control such
patients.
• A detailed investigation for causes of difficult to
treat asthma should be undertaken by a specialist.
Usual Pediatric Doses (mcg)
for Inhaled Corticosteroids
Drug
Low
Medium
High
BDP(42 ug/p)
84-336
336-672
> 672
FLUN(250 ug/p)
500-750
1,000-1,250
>1,250
TAM(100 ug/p)
400-800
800-1,200
>1,200
FP(44/110/220/p)
88-176
176-440
>440
BUD(200ug)
100-200
200-400
>400
BDP- Beclomethasone dipropriate, Flun- Flunisolide, BUD- Budesonide
TAM- Triamcinolone, FP-Fluticasone proprionate,
Which Asthma Patients Should Be
Referred to an Asthma Specialist?
• History of life-threatening exacerbation
• Treatment goals not met after 3-6 months
• Atypical Sx/signs, or uncertain diagnosis
• Significant comorbidities
– VCD, sinusitis, polyps, ABPA, GERD, COPD
• Additional diagnostic testing indicated
Which Asthma Patients Should Be
Referred to an Asthma Specialist?
• Consideration for immunotherapy
• Requirement for step 4 care or higher
• Hospitalization for asthma
• Requirement for  2 steroid courses in 1 yr
• Suspected occupational/environmental contribution
• Psychiatric/psychosocial/family problems
Expert Panel Recommendations for
Elements of Each Follow-up Visit
• Ask patients what concerns they have about their
asthma and what they especially want addressed
during the visit?
• Review the short-term goals agreed on in the initial
visit.
• Review the written action plan.
• Continue teaching and reinforcing key educational
messages.
• Give patients brief, written materials.
Pharmacist’s Role in a Comprehensive
Asthma Disease Management Program
• Provide patient focused education on
medication efficacy and side effects
– Review and instruct on optimal delivery
– Pharmacy database review to identify poor
adherence to refills and B2 abuse
Pharmacist’s Role in a Comprehensive
Asthma Disease Management Program
• Educate patients about asthma medications.
• Instruct patients about the proper techniques for
inhaling medications.
• Monitor medication use and refill intervals to help
identify patients with poorly controlled asthma.
• Encourage patients purchasing OTC asthma
inhalers or tablets to seek medical care
• Help patients use peak flow meters appropriately.
• Help patients discharged from the hospital
understand their asthma management plan.
NMCSD Pediatric Asthma Hospitalization Rate vs.
Healthy People 2000 and 2010 Benchmarks
Pediatric Asthma
Admissions / 10,000
45
NMCSD
40
HP 2000
35
HP 2010
30
25
20
15
10
5
0
1996
1997
1998
1999
2000
Year
2001
2002 2003 2004 2005 2006
NMCSD Emergency Department Pediatric
Asthma Visits
600
E.D Asthma Visits
ED Visits
500
400
300
200
100
0
1999
2000
2001
2002
Fiscal Year
2003
2004
2005
2006
Naval Medical Center San Diego Pediatric Asthma
Inpatient Cost Savings Compared to Fiscal Year 1996
1000000
Net Savings 97-03’- $4,087,500
800000
600000
400000
200000
0
1996 1997 1998 1999 2000 2001 2002 2003
Fiscal Year
MY ASTHMA CARE
GUIDE
Seven Steps to Optimal Asthma Care:
1. Ask about a written Home Asthma Action Plan
and instructions on its use.
2. Receive an influenza immunization each fall.
3. If older than 5, have lung function testing every
1-2 years.
4. If you are having asthma symptoms (cough,
wheeze, chest tightness, chest pain, shortness
of breath, difficulty breathing) more than 2
days per week and/or 2 nights per month, your
asthma IS NOT Controlled….contact your
Asthma Care Provider promptly.
5. Take controller medications daily even when
you feel well and never run out of refills.
6. For severe symptoms not responding to
abuterol, seek immediate medical care.
7. Regardless of asthma severity, your asthma
care provider should reevaluate you at least
every 6-12 months.
My Asthma Medications
Controllers- These medicines are preventative and are to
be used EVERYDAY, regardless of how you feel.
? Flovent (orange) ____ mcg ___ puff(s) ___times a day
? Aerobid (purple) ___ _ mcg ___ puff(s) ___times a day
? Azmacort (white)____ mcg ___ puff(s) ___times a day
? Pulmicort (white)____ mcg___ puff(s) ___times a day
? Pulmicort Respules ____ mcg nebulized
? Serevent (green) ____ mcg ___ puff(s) ___times a day
? Advair (purple)____ mcg ____ puff(s) ___ times a day
? Singulair 4 mg 5 mg 10 mg tablet Take one by mouth
before bed.
Rescue Inhalers- For use with symptoms of shortness of
breath, cough or wheeze.*
? Albuterol ____ puff(s) ____times a day as needed for
asthma symptoms
- also called Proventil or Ventolin
* Always use your Valved Holding Chamber with a metered dose inhaler.
Other meds:_____________________________________
_______________________________________________
_______________________________________________
Common Asthma Triggers
1. Smoke including tobacco, fireplace
and barbecue
2. Dust mites
3. Indoor mold
4. Animal dander
5. Cockroach droppings
6. Pollen
7. Strong odors including perfumes
8. Exercise
9. Cold air
10. Viral and bacterial upper respiratory
infections
11. Aspirin and non-steroidal medications