Evidence Based Asthma Diagnosis and Management 2007 EPR CPG
Update Henry A. Wojtczak, M.D. [email protected]
Slide 3
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
Slide 4
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
Burden of Disease General Over 300 million asthmatics worldwide
1 20.5 million Americans have Asthma 2 Approximately 6.5 million
children are affected 2 10.6 million individuals experienced an
asthmatic episode during the previous 12 months Nearly 500,000
hospitalizations for asthma anualaly in the US 1.Allergy 2004
Global Burden of Asthma: 59; 469-478 2.National Center for Health
Statistics. Raw Data from the National Health Interview Survey, US,
(2005)
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Burden of Disease Death Rate, 1979 to 1997 0.8 1 1.2 1.4 1.6
1.8 '79'80'81'82'83'84'85'86'87'88'89'90'91'92'93'94'95'96'97 Male
+ Female Male Female Deaths per 100,000 Population 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)
Slide 8
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
Slide 9
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
Slide 10
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)
Slide 11
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.
Slide 12
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
Slide 13
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)
Slide 14
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
Slide 15
Spirometry Diagnosis Classically, see a low FEV 1 (amount of
air expired in one second with maximal effort) with a decreased FEV
1 / 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, FEV 1, or FEV 1 /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.
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
Slide 20
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
Slide 21
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 pre-
treatment
Slide 22
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, FEV 1 ). studies suggest up to 70%
improvement in symptoms. Fundoplication may provide even better
results than medical management.
Slide 23
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).
Slide 24
Asthma: Making the Diagnosis Differences from 1997 & 2002
guidelines Emphasis on spirometry Preference over peak flow for
diagnosis Inclusion of FEV 6 as well as FVC Recommended in children
> age 4
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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
Slide 26
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)
Slide 27
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.
Slide 28
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
Slide 29
Assessment The key elements of assessment and monitoring are
refined to include the separate, but related, concepts of Severity
Control Responsiveness to treatment
Slide 30
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
Slide 31
Severity Classification Severity classification is defined in
terms of two domainsimpairment and riskto emphasize the need to
consider separately asthmas 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.
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Severity Classification New parameters for pulmonary function
measuresFEV1/FVChave 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.
Slide 33
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).
Slide 34
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.
Slide 35
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 guidelines 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 self- management education.
Slide 36
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
Slide 37
Medications Information about asthma medications has been
updated based on review of evidence published since 1997. This
updated report (EPR3) continues to emphasize that the most
effective medications for long-term therapy are those shown to have
anti-inflammatory effects. New medicationsimmunomodulatorsare
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.
Slide 38
Medications Recommendations for managing asthma in children 04
and 511 years of age are presented separately from recommendations
for managing asthma in youths >12 years of age and adults.
Treatment decisions for initiating long-term- control 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 04 years of
age have been revised
Slide 39
Medications Treatment decisions for adjusting therapy and
maintaining control are based on assessing the level of asthma
control (considering separately asthmas 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.
Slide 40
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 04 years age group; for other age groups (children
511 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 56 for youths 12 years of age and adults
include consideration of omalizumab. Managing special situations
has been expanded to include racial and ethnic disparities.
Slide 41
Exacerbation Management For the assessment of exacerbations,
the current update (EPR3): 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
(4069 percent predicted); and the exacerbation severity level where
adjunct therapies may be considered (
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
Slide 72
Relative Risk of Hospitalization in the United States Donahue
et al. JAMA. 1997;277:887-891. Prescriptions per person-year
Relative Risk None1-22-33-55-88+0-1 2 -agonists Total ICS 0 1 2 3 4
5 6 7 8 Age 0-17 Age 18-44 Age 45+ Total Age 0-17 Age 18-44 Age
45+
Slide 73
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
Slide 74
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 respiratory- and asthma-related
deaths and life-threatening experiences in salmeterol group These
adverse events were more frequent in African- American patients,
especially if not also taking inhaled corticosteroids *Nelson HS et
al, Chest 2006;129:15-26
Slide 75
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
Slide 76
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
Slide 77
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
Slide 78
Step Therapy Age 0-4 years
Slide 79
Step Therapy Age 5-11 years
Slide 80
Step Therapy Age 12 years +
Slide 81
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.
Slide 82
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.
Slide 83
Intermittent 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
Slide 84
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.
Slide 85
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.
Slide 86
Moderate Persistent These are patients with daily symptoms, or
baseline FEV 1 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 low- dose ICS
Slide 87
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.
Slide 88
Meta-analysis Clinic FEV 1 at 6 Months Favors increasing ICS
Ind Greening Woolcock Kelsen Murray Kalberg Condemi van Noord (LD)
van Noord (HD) Vermetten Fixed effects Random effects Treatment
difference (L) Favors adding salmeterol -0.250.000.25-0.500.50
Adapted from Shrewsbury et al. Br Med J. 2000;320:1368-1373.
Slide 89
Meta-analysis Mean Percentage of Symptom-Free Days at 6 Months
-10010304020 Ind Greening Woolcock Kelsen Murray Kalberg Condemi
van Noord (LD) van Noord (HD) Vermetten Fixed effects Random
effects Treatment difference (%) Favors adding salmeterol -30-20-40
Favors increasing ICS Adapted from Shrewsbury et al. Br Med J.
2000;320:1368-1373.
Slide 90
Run-in FP 100 mcg inhalation powder BID FP 100 mcg BID + MON 10
mg QHS (n=225) 3 weeks12 weeks FP/SP DISKUS 100/50 BID (n=222)
Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095. FP/SAL
DISKUS 100/50 vs FP 100 mcg + Montelukast 10 mg Study Design
Patients: 15 years of age Baseline FEV 1 50%-80% of predicted
Symptomatic on ICS MON, montelukast
Slide 91
FP/SAL DISKUS 100/50 vs. LTRA: AM PEFR Nelson et al. J Allergy
Clin Immunol. 2000;106:1088-1095. Baseline AM PEF: FP/Sal DISKUS
100/50 = 398 L/min; FP + MON = 392 L/min. *P 0.001 vs FP + MON at
Endpoint. Mean Change from Baseline in AM PEF (L/min) Day Endpoint
(last evaluable measurement) FP/SAL DISKUS 100/50 BID FP 100 mcg
BID + MON 10 mg QD * 714212835Baseline42495663707784
Slide 92
FP/SAL Discus vs. MON 10: Rescue Albuterol Use Nelson et al. J
Allergy Clin Immunol. 2000;106:1088-1095. Baseline albuterol use
(puffs/day): ADVAIR DISKUS 100/50 = 3.77; FP + MON = 3.73. *P=0.004
vs FP + MON at Endpoint. Mean Change from Baseline in Rescue
Albuterol Use (puffs/day) Endpoint Week * FP/SP DISKUS 100/50 BID
FP 100 mcg BID + MON 10 mg QD 12345Baseline6879101211 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.
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
Slide 98
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
Slide 99
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.
Slide 100
Pharmacists 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 B 2
abuse
Slide 101
Pharmacists 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.
Slide 102
NMCSD Pediatric Asthma Hospitalization Rate vs. Healthy People
2000 and 2010 Benchmarks Year Pediatric Asthma Admissions / 10,000
0 5 10 15 20 25 30 35 40 45 1996199719981999200020012002 NMCSD HP
2000 HP 2010 20032004 20052006
Slide 103
ED Visits Fiscal Year NMCSD Emergency Department Pediatric
Asthma Visits 0 100 200 300 400 500 600 1999200020012002 E.D Asthma
Visits 2003 2004 20052006
Slide 104
Net Savings 97-03- $4,087,500 Naval Medical Center San Diego
Pediatric Asthma Inpatient Cost Savings Compared to Fiscal Year
1996