Download Describe the highest risk asthma populations

Asthma
The Challenge of Children, Minorities,
and Low-Income Populations
Thomas Owens, MD
Asthma: A Chronic Lung Disease
• Characterized by recurrent cough and
wheeze that is increasing in prevalence
among children
• From 1980 to 1996
– the number of Americans afflicted with asthma
more than doubled to 15 million
– with children under 5 experiencing the highest
rate of increase
This constitutes an epidemic
Review of Asthma
A.D.A.M., 2007
Objectives
• Describe the highest risk asthma populations
• Outline the significant features of the asthma
management guidelines
• Describe adherence issues and methods to
overcome difficulties
• Describe new advances in the diagnosis and
pharmacological treatments of asthma
Objectives
• Describe the highest risk asthma
populations
• Outline the significant features of the asthma
management guidelines
• Describe adherence issues and methods to
overcome difficulties
• Describe new advances in the diagnosis and
pharmacological treatments of asthma
Prevalence in High-Risk
Populations
Nearly 5 million children
(<5% population 18 & younger)
African-Americans &
Hispanic Americans
(Highest rates of asthma)
Urban areas with
poor living conditions
(near transportation and industrial activity)
Low SES (<$20,000/yr)
(Carmago,2007)
(poor access to healthcare and education)
(Morris, 2007)
Children with Asthma
• Usually begins in early childhood (Carmago, 2007)
– 80-90% have symptoms by age 6
– > ½ develop by age 3
– < 10 yrs. male-to-female ratio is 2:1
• Between the ages of 18 and 54 years the ratio is
reversed
(University of Aberdeen, 2007)
Ethnicity Prevalence
• Caucasian children lowest at risk (Sharma,2007)
– African-Americans 44% higher
• 5-8% have asthma at sometime
• 20-25% of inner-city children
– Hispanics 15% higher
• 20-25% of inner-city children
• U.S. average prevalence:
– 7.6%, with ethnic minority
prevalence of 3-14%
Caucasian
A fr ican A mer ican
H ispanic
African-American Child
Hospitalizations
• African-American children are
hospitalized 3 times more than
Caucasians (Bolte, 2007)
– 1998 statistics: African-Americans
more than 4 times likely to die
– Mortality rates doubled 1980 to 1996
– More deaths occur in inner city areas
Mortality Rates in
Pediatric Asthma
• More than doubled between 1980 and 1996
– disproportionate number of deaths occur in inner city areas
• There are 5,000 deaths annually from asthma
– some have been linked to management failure (especially in
younger persons)
– highest mortality rates occur in adolescents
– persons who have had prior asthmatic exacerbation
requiring intubations are at significantly increased risk for
subsequent fatal exacerbations (Morris, 2007)
Significant Factors in Pediatric
Asthma Deaths
• Inappropriate delay in seeking medical
attention
• Limited access to care
• Under-use of anti-inflammatory agents
• Overuse of beta agonists
(Morris, 2007)
Barriers to Healthcare: Inner City
Residents
• Inner city inhabitants may:
–
–
–
–
low income
medically underserved
less likely to have routine doctor visits
poor access to the availability of medications
(Morris, 2007)
The source of primary and follow-up care for
this population is often in the hospital
emergency department.
Barriers to Healthcare: Ethnic
Minorities
• Lower quality health care
– even when insurance, age, income and severity
of conditions are the same
• Tend to use inhaled corticosteroid
suppressants less than Caucasians
• Results from cost, inadequate literacy or
competing priorities
– These patients also received less follow-up after
hospital emergency department visits (Morris, 2007)
Barriers to Asthma Management
• Asthma is a disease that requires
maximum cooperation of the patient
and family
• Parents must oversee a complicated
regimen of inhalers, pills, and breathing
exercises
(Morris, 2007)
– this type of supervision and assistance
may not be available in poverty situations
Cultural Asthma Research
• Cultural competence policies and other predictors of
asthma care quality for Medicaid-insured children (Lieu,
2004)
– evaluated medical clinics serving primarily inner city
patients
– best management of asthma was rendered where:
•
•
•
•
•
•
physicians and caregivers improved their communication skills
were trained in cultural differences
utilized bilingual or low-literacy instructions, posters, teaching
medication feedback was encouraged
asthma case managers were utilized
ethnic minority caregivers were employed
Latino Populations
• Puerto Ricans having highest mortality
rates
– followed by Cuban Americans and
Mexican Americans (Homa et al. 2000; Sly, 2006)
The Effect of Urbanization
• Asthma emergency visits account for approximately
2% of all emergency visits
– In urban centers acute asthma may comprise up to 10% of
all emergency visits
• Worldwide, 130 million people have asthma
– The prevalence is 8-10 times higher in developed,
industrialized countries (like Canada, England, Australia,
Germany and New Zealand; prevalence rate = 2-10%) than in the
developing countries. (Morris, 2007)
– In developed countries, the prevalence is higher in low
income groups in urban areas and inner cities than in other
groups
– Prevalence increases as a developing country becomes
more Westernized and urbanized
Environmental Factors
• Exposure to maternal environmental
tobacco smoke
– which during pregnancy or the first year
appears to predispose children to reactive
airway disease
• Efforts to mitigate cockroach and mold
reduced symptoms successfully and
significantly for urban children
(Morgan et al., 2004)
Status Asthmaticus
• Appears to be on the rise
• Several retrospective studies reflect an
increase in hospital admissions
– particularly in those younger than 4 years
• Fewer hospital and emergency visits
are needed in children using inhaled
corticosteroid therapy
Urbanization Pollution
• Main contributor to the development of
this disease
– Gasoline (car) & diesel fuel (truck)
combustion engines produce similar and
yet different types of respiratory toxins
(Pandya, 2001)
Gasoline Exhaust
• Produces known pollutants and several
components of air pollution have been linked
to asthma
• U.S. Clean Air Act requires the EPA to
monitor:
– nitrogen dioxide, sulfur dioxide, lead, carbon
monoxide and ozone particulate matter (both
PM(10 microns (um)) and PM(2.5)
– diesel exhaust and diesel exhaust particles
(DEPs) also appear to play a role in respiratory
and allergic diseases (Pandya, 2001)
Diesel Exhaust
• Smog-forming and toxic air pollutant
vapors and gases that you get when
you burn gasoline
– also composed of small particles of
carbon, known as fine particulate matter
and also referred to as
Diesel Exhaust Particles (DEPs)
(Johnson, 2007; Graham, 2007)
Diesel Particulates
• EPA classifies and measures these
particulate matter according to their size
– (PM2.5 = 2.5 microns (micromenter, um), PM 10
= 10 microns)
• Unfortunately, the average diameter of diesel
particulates is 0.2 microns, and nearly 94%
of diesel particulates have diameters less
than 2.5 micrometers (um) (Johnson, 2007; Graham, 2007)
Tiny Toxins
EPA, 2007
DEPs
• Hundreds of chemicals adsorbed to their
surfaces
• Cooked but unburned hydrocarbons could
combine in thousands of combinations or
permutations
– are large, complex, carbon-ringed, planar, lipid
soluble
– similar to those we find in nature or design to
penetrate the cell walls and enter the nucleus to
interact with DNA (Pandya, 2001)
DEPs
• Bind to airborne allergens and other
debris
– may alter these complex organic allergen
molecules further (Pandya, 2001)
One could not design a more effective
delivery method or toxic product to
enter the deepest of our lungs
Diesel Emissions
• Include over 40 substances that are listed by
the EPA as hazardous air pollutants
• Federal agencies have classified diesel
exhaust as a probable human carcinogen
• Benzene, an important component of the fuel
and exhaust
– is designated to be a known human carcinogen
(Pandya, 2001)
Polyaromatic Hydrocarbons
• Contain larger, more complex
– (anthracene, fluoranthene, pyrene, phenanthrene)
• In addition, DEPs contain
– aldehydes (formaldehyde, acetaldehyde,
acrolein), benzene, 1,3-butadiene, polycyclic
aromatic hydrocarbons (PAHs), nitro-PAHs and
hundreds of others
Diesel exhaust ranks among the air
pollutants that EPA believes pose the
greatest public health risks
(Pandya, 2001)
Diesel Exhaust Components
• Genotoxic and mutagenic
– can produce symptoms of allergy
• including inflammation and irritation of airways
• Exposure to diesel exhaust can cause
lung damage and respiratory problems
– diesel exhaust can also exacerbate
asthma and existing allergies
– long-terms exposure is thought to increase
the risk of lung cancer
(Pandya, 2001)
Children & Air Pollution
There is no known safe level of exposure to
diesel exhaust for children, especially
those with respiratory illness
• May be more susceptible to air pollution
– they breathe 50 % more air per lb. of body weight
than adults
• May be especially susceptible to DEPs due
to the small size of the particle
– Smaller particles are able to penetrate children’s
narrower airways reaching deeply within the lung,
where they are more likely to be retained
(Pandya, 2001)
DEPs
• DEPs act as generic respiratory irritant at
high concentrations
• At lower levels:
– DEPs act as pro-inflammatory agents
– promote release of specific cytokines,
chemokines, immunoglobulins, and oxidants in
the upper and lower airway
– DEPs cause formation of reactive oxygen species
that trigger pro-inflammatory cytokine release
(Takizawa, 2007)
Immunologic Evidence
• May help explain the epidemiologic
studies indicating that children living
along major trucking thoroughfares are
at increased risk for:
– asthmatic and allergic symptoms
– more likely to have objective evidence of
respiratory dysfunction
(Pandya, 2001)
New & Emerging Factors
U.S. Trends in Diesel Fuel
Consumption
30 Billion Gallons Per Year
This figure demonstrates a 45%
increase in diesel fuel consumption in
the U.S. over the past decade.
As newer diesel engines emit less
pollution, total pollution may still
increase in response to increasing
numbers of vehicles on the highway,
and increasing miles driven by diesel
vehicles.
Wargo, 2002
School Bus Study Statistics
• U.S. nearly 600,000 school buses transport 24
million students to school daily
• Each year buses travel 4.3 billion miles
– nearly 10 billion school bus rides
– students will spend 180 hours on buses each year
– children spend 3 billion hours on school buses each year
• More than 99% of U.S. school buses are powered by
diesel fuel
• Fine particulate concentrations measured on buses
in this study were often 5-10 times higher than
average levels (Morris, 2007)
School Bus DEPs
• Levels of DEP often higher under certain
circumstances: (Morris, 2007)
–
–
–
–
were idling with windows opened
ran through their routes with windows closed
moved through intense traffic
queued to load or unload students while idling
• Some studies show there would have been
less exposure if you ride in the vehicle
directly behind the bus than to ride in it
NRDC & Coalition for Clean Air
Study (2001)
• Shows that children who ride a diesel school
bus may be exposed to up to four times
more toxic diesel exhaust than someone
traveling in a car directly behind it
• Excess exhaust levels on school buses were
23 to 46 times higher than levels considered
to be a significant cancer risk
– according to the U.S Environmental Protection
Agency and federal guidelines (Morris, 2007)
Additional Causes of Asthma
• Exposure to:
– passive smoking
– changes in exposure to environmental allergens
• cockroaches, house dust mites, and the mold Alternaria
Tenuis
• other aeroallergens like pet dander, gas and woodburning stoves and tobacco smoke
– viral respiratory infections
• caused by respiratory syncytial virus
• possibly rhinovirus are a significant risk factor for the
development of childhood wheezing in the first decade
of life (Morris, 2007)
Chronic Noise Levels
• During sleep caused stress and
resulted in higher cortisol levels in the
first half of the night
• Noise may have an adjuvant effect on
the pathogenesis of allergies
Genetics
• Found more often in patients with a
personal or family history of atopy
• Family history of asthma (Risk)
– 7% if neither parent has asthma
– 20% if one parent has asthma
– 64% if both parents have asthma (Chin, 2001)
Allergic March
• Infants exhibiting
– atopic dermatitis
– food intolerance
• Followed in time by allergic
rhinoconjunctivitis
• Ending with development of asthma
Hygiene Hypothesis
• Proposes that newborns are armed with an
immune system ready to respond to natural
environmental and infectious stimuli
• If not exposed to these
– the balance of T lymphocytes will be tilted
towards a more ‘angry’ reactive population TH2
– as opposed to a ‘relaxed’ TH1 population with all
their cytokine messenger signal proteins
Measles Infection
• BCG vaccine administration
• Hepatitis A seropositivity
• Other stimuli that increase production
of interferon-gamma
• IL-12 may inhibit the TH2 allergic
response
Increased Atopy & Asthma
• Increased atopy and asthma associated with:
– Vaccinations, fewer childhood infections, liberal use of
antibiotics, more processed food in diets, smaller families,
and less exposure to day care environments
– Prevalent in western Germany, while bronchitis from power
plants is more common in eastern Germany
• Chinese from Hong Kong had higher atopy/allergy
levels than those living on the mainland
• Traffic police officers had higher atopy/allergy levels
than those with desk jobs (Polosa, 2002)
Further Asthma Study Results
• Twins raised separately
– farm-reared sibs had lower asthma levels than
town-raised sibs
• Asthma-free areas are present in certain subSaharan areas
– Somalia, where hookworm disease is endemic
• The parasitic system (eosinophiles) is fully
engaged
Questions
• Could it be that the reactive immune
system engages what it has available,
(eg. cockroach, mold, cat antigens)?
• And the adjuvant effect of air pollution
and DEPs turns on the immune
reaction to a high level?
Let’s Review!
Children may be more susceptible to
diesel exhaust particles (DEPs)
because:
A. Small size of the
DEP particles
B. Pro-inflammatory
agents in the DEPs
C. High breathing rate
Objectives
• Describe the highest risk asthma populations
• Outline the significant features of the
asthma management guidelines
• Describe adherence issues and methods to
overcome difficulties
• Describe new advances in the diagnosis and
pharmacological treatments of asthma
National Asthma Education &
Prevention Program (NAEPP)
• National Heart, Lung, and Blood
Institute (NHLBI) of the National
Institutes Health has assembled:
• Best practice guidelines for diagnosis and
treatment of asthma
– 2007 revision available:
• http://www.nhlbi.nih.gov/guidelines/asthma/epr
3/resource.pdf
Asthma Diagnosis
• Confirmed with recurrent wheezing,
coughing, dyspnea
– Objective PEFR reversibility with
medication
• Asthma staging helps define
management, continued monitoring of
symptoms
– PEFR helps adjust medication
Goals of Treatment
1. Reduce wheeze and cough
2. Reduce the risk and number of acute
exacerbations
3. Minimize adverse effects
– medications
– sleep disturbances
– absences from school
NAEPP Effective Asthma
Management Components
1. Objective measurement of lung
function
2. Environmental control measures
3. Comprehensive pharmacology
therapy
4. Patient education
Peak Flow Meter
• Peak flow readings (PEFR) twice daily
and as needed
– Green > 80%
• Okay
– Yellow 50 - 80%
• Action plan
– Red < 50%
• Emergency call
Digital Peak Flow Meter
• Electronic peak flow meters
– will collect and monitor the data for the patient
– data can be reviewed manually or electronically
• Results can be downloaded to a computer
and produced in a graph or tabular format
– ability to track and trend data
Microlife Digital Peak Flow Meter, 2007
Indoor Pollutants
(northernnaturals.com, 2007)
Environmental Control
• Removal of carpeting and the use of pillow
and mattress covers
– However, recent evidence from better quality
studies has shown that dust-mite avoidance
measures did not improve symptoms or reduce
medication use in adults with moderate to severe
asthma.
• Air filtration systems
– There is insufficient evidence to recommend for or
against the use of air filtration units to reduce
allergen levels in an effort to improve asthma
symptoms.
Halken, et al., 2003; Woodcock,, et al., 2003; Terreehorst,, et al., 2003;
Kilburn, 2004
Other Allergen Controls
• Cockroach trappings
• Remove moisture to lessen mold
• Washing pets
– cats twice a week
• Skin testing
• Immunotherapy
Halken, et al., 2003; Woodcock,, et al., 2003; Terreehorst,, et al., 2003;
Kilburn, 2004
Long-Term Management of Asthma in Children
Go into objective
Asthma
classification*
Medications
required to maintain
long-term control
Symptom frequency
Lung function†
Mild intermittent
Daytime: 2 days per week
or less
Nighttime: 2 nights per
month or less
PEF or FEV1: 80 percent
or more of predicted
function
No daily medication needed
Mild persistent
Daytime: more than 2
days per week, but less
than 1 time per day
Nighttime: more than 2
nights per month
PEF or FEV1: 80 percent
or more of predicted
function
Low-dosage inhaled
corticosteroid delivered by
nebulizer or metered-dose
inhaler with holding chamber,
with or without a face mask, or
by dry-powder inhaler in
children 5 years and younger
Moderate persistent
Daytime: daily
Nighttime: more than 1
night per week
PEF or FEV1: 60 to 80
percent of predicted
function
Children 5 years and younger:
low-dosage inhaled
corticosteroid and long-acting
beta2 agonist or mediumdosage inhaled corticosteroid
Children older than 5 years:
low- to medium-dosage
inhaled corticosteroid and
long-acting inhaled beta2
agonist.
Severe persistent
Daytime: continual
Nighttime: frequent
PEF or FEV1: 60 percent
or less of predicted
function
High-dosage inhaled
corticosteroid and long-acting
beta2 agonist
PEF = peak expiratory flow; FEV1 = forced expiratory volume in one second. *-Clinical features before treatment or adequate control. †-Lung function measurements are used only in patients older
than five years. Adapted from National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002.
Bethesda, Md.: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 2003; NIH publication no. 02-
Usual Dosages for Quick-Relief Asthma Medications
Medication
Dosage Form
Child Dosage*
HFA MDI with spacer: 90 mcg per puff, 200
puffs
1 to 2 puffs every 4 to 6 hours as
needed.
Nebulizer solution: 5 mg per mL (0.5
percent), 3.5 mg per 3 mL, 1.25 mg per 3
mL, 0.63 mg per 3 mL
0.05 mg per kg (minimum 1.25 mg,
maximum 2.5 mg) in 3 mL of saline
every 4 to 6 hours.
MDI with spacer: 18 mcg per puff, 200 puffs
1 to 2 puffs every 6 hours
Nebulizer solution: 0.25 mg per mL (0.025
percent)
0.25 to 0.5 mg every 6 hours
Nebulizer solution: 0.31 mg per 3 mL, 0.63
mg per 3 mL, 1.25 mg per 3 mL
0.025 mg per kg (minimum 0.63 mg;
maximum 1.25 mg) every 4 to 8
hours
Methylprednisolone
(Medrol)
2-, 4-, 8-, 16-, and 32-mg tablets
0.25 to 2 mg per kg in the morning
or every other day, as needed for
control
Short-course "burst”: 1 to 2 mg per
kg per day (maximum 60 mg per
day) for 3 to 10 days
Prednisolone (Delta-Cortef)
5-mg tablets
Syrup: 5 mg per 5 mL, 15 mg per 5 mL
Same as methylprednisolone
Prednisone
1-, 2.5-, 5-, 10-, 20-, and 50-mg tablets
Syrup: 5 mg per mL, 5 mg per 5 mL
Same as methylprednisolone
Inhaled medications
Albuterol (Proventil)
Ipratropium (Atrovent)
Levalbuterol (R-albuterol,
Xopenex)
Systemic corticosteroids
HFA = hydrofluoroalkane; MDI = metered dose inhaler. *-Dosages are for children 12 years or younger unless otherwise specified. Adapted from National Asthma Education and Prevention Program.
Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002. Bethesda, Md.: U.S. Department of Health and Human Services, Public Health
Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 2003. NIH publication no. 02-5074:120-1.
Let’s Review!
Part of the treatment for all 4 levels of
asthma include:
A.
B.
C.
D.
Quick acting beta2 agonist
Leukotriene inhibitors
Theophylline
Long-acting beta2 agonist
Objectives
• Describe the highest risk asthma populations
• Outline the significant features of the asthma
management guidelines
• Describe adherence issues and methods
to overcome difficulties
• Describe new advances in the diagnosis and
pharmacological treatments of asthma
Adherence Issues
• The patient’s understanding of asthma
treatment and exacerbating factors is
key to asthma control
Patient education is key in
this chronic disease
Prevalence Methods
• Education
– Patient and caregiver empowerment
• Emphasize controller medications
– Enact an action plan
• (Patients do not like to take meds when they are feeling well)
• Overcome cultural and communication barriers
– Use available tools
• Clean Air Act
– Now LAW
• Pollution activism
– Where you live!
Asthma Tool Kit
• Inner City Asthma Intervention (NIH)
– www.achp.org
• Select ACHP foundation
• Then click “tool kit”
Offers advice based on
“best practices”
Cross-Cultural Competence
Communication Skills
• Promote bilingual or illiterate education
– Handouts, posters, etc.
• Ethnic minority caregivers-language
ability, understand cultural barriers
– Highly important!!
• Emphasize controller medications
– Monitor beta2 agonists (Lieu, 2004)
Encouraging Action
• Case managers
– reports to clinicians
– provide support for self-care
– use asthma management guidelines
• Encourage patient empowerment & selfmanagement with feedback
• Encourage
– primary care access, continuity, coordination
Managed care can support and
benefit from this activity
(Lieu, 2004)
Educational Empowerment
•
•
•
•
Recognize and avoid triggers
Understand use of prescribed medications
Proper use of inhalation devices
Importance of compliance and monitoring:
– shown to improve lung function
– decrease school absenteeism and visits to the emergency
department
– children with moderate to severe asthma receive the most
benefit from educational programs
(Haby, 2004)
However, education for children who have received
emergency department care for asthma does not reduce
subsequent emergency department care, hospitalizations,
or unscheduled doctor visits.
Let’s Review!
Features of best practice asthma
management for all persons include:
A.
B.
C.
D.
Education in your language about disease process
and methods of monitoring and treatment
Peak flow meter education and usage in disease
monitoring and treatment
Action plan based on PEFR
Follow up for disease Rx adjustment as needed
Objectives
• Describe the highest risk asthma populations
• Outline the significant features of the asthma
management guidelines
• Describe adherence issues and methods to
overcome difficulties
• Describe new advances in the diagnosis
and pharmacological treatments of
asthma
Latest Rx Advancements
• Rescue beta2 agonists
– Use MDI with spacer-paper cup or
plastic soda bottle if must
(NAEPP, 2002)
• (as good as nebulizer)
**Use facemasks in under 5
(Cleveland Clinic Health System, 2007)
Latest Rx Advancements
• More severe attacks
– Use anticholinergics with beta2
agonists
(NAEPP, 2002)
(www.asthme-queec.ce, 2007)
Latest Rx Advancements
• To keep controller inhaled steroids
at lowest required dose
– Use leukotriene modifiers and
nedocromil
(NAEPP, 2002)
(www.asthme-queec.ce, 2007)
Latest Rx Advancements
• To reduce the likelihood of hospital
admission
(NAEPP, 2002)
– Give oral corticosteroids early during
an acute asthma exacerbation
• (i.e., within 45 minutes of the onset of
symptoms)
(www.asthme-queec.ce, 2007)
Oral Corticosteroids
• More effective than inhaled or nebulized
corticosteroids
– children hospitalized with severe acute asthma
• Treatment of acute flares of asthma with repeated
short courses of oral corticosteroids
(NAEPP, 2002)
– (at a dose of 1-2 mg per kg per day)
– do not appear to cause any lasting changes in bone
metabolism, bone mineralization, or adrenal function
No evidence that intravenous corticosteroids are any
more effective than oral corticosteroids in children
with an intact and functioning digestive tract
Inhaled Corticosteroids
• High doses reduce hospital admission
rates
– In patients with acute asthma
(Courtney, 2005)
However, there is insufficient evidence
that inhaled corticosteroids alone are
as effective as systemic steroids
Inhaled Corticosteroids
• As a single agent in a medium dosage are more
effective than:
– Inhaled long-acting beta2 agonists
– Inhaled nedocromil (Tilade), and leukotriene inhibitors
• (In improving asthma symptoms and lung function in children
with mild to moderate asthma)
• Use of maintenance inhaled corticosteroids
– Less use of bronchodilators and oral corticosteroids in
patients using reduced growth velocity
(NAEPP, 2002)
However, multiple studies have found no evidence
that children treated prophylactically with inhaled
corticosteroids fail to reach their full adult height.
Inhaled Corticosteroids
• Unlike adults, children whose asthma is
inadequately controlled with standard
dosages of inhaled corticosteroids
have:
– not been shown to benefit from the
addition of a long-acting beta2 agonist
– or from an increase in the dosage of
inhaled corticosteroids
(NAEPP, 2002)
Rx Research Findings
• Doubling the dosage of beclomethasone
– did not change objective measures of lung function
– or symptom scores but did result in a significant reduction of
growth velocity
(NAEPP, 2002)
Some benefit can be achieved with the addition of oral
theophylline, but long-term effects have not been assessed.
• A brief, four-week study of oral montelukast
(Singulair) added to standard dosages of inhaled
budesonide (Rhinocort Aqua) in children whose
asthma was not adequately controlled demonstrated:
– improved lung function
– reduction in the number of days with asthma exacerbations
Leukotriene Inhibitors
• Studies have shown that:
– optimizing the dosage of inhaled corticosteroids provides
better control of asthma than oral montelukast
• However another study found:
– montelukast and inhaled corticosteroids were equally
effective
• possibly because of significantly better adherence with oral
montelukast therapy
• Compared with placebo:
– oral montelukast reduces
• total daily use of beta2 agonists
• the need for rescue oral corticosteroids
• daytime symptom scores
Ducharme & Di Salvio, 2004; Knorr et. at.,
1998, 2001, 2003
Nedocromil & Cromolyn
• Inhaled nedocromil reduces:
–
–
–
–
–
asthma symptom scores
asthma severity
bronchodilator use
improves lung function compared with placebo
However, it is not as effective as inhaled corticosteroids
• There is insufficient evidence to recommend
prophylactic treatment with inhaled cromolyn (Intal)
in children
– Although it has been studied for use in children with
asthma, it is less effective than inhaled corticosteroids in
improving symptoms and lung function
Armenio, 1993; Tasche, 2000
Levalbuterol R-albuterol
(Xopenex)
(xopenex.com, 2007)
Levalbuterol R-albuterol
(Xopenex)
• Bronchodilator that contains R and S isomers
of albuterol
– The R-albuterol is responsible for the bronchodilator effect
– The S-albuterol provides no benefit and may be responsible
for the albuterol side effects
• Several pediatric studies have supported the
use of levalbuterol over racemic albuterol
– (increase FEV1, more favorable safety profile with fewer
side effects)
(Carl, 2003)
– Two conflicting studies do not support these findings
Overall, a review of levalbuterol for the treatment of asthma in
children found no clinically significant advantage over racemic
albuterol.
Omalizumab (Xolair)
(Xolair.com, 2007)
Omalizumab (Xolair)
• Recombinant DNA-derived humanized IgG
monoclonal antibody that selectively binds to human
immunoglobulin E (IgE)
– Inhibits the binding of IgE to the high-affinity IgE receptor on
the surface of mast cells and basophils, limiting release of
allergic mediators
– Omalizumab is approved for use in children 12 years and
older with moderate to severe persistent asthma
• who have a positive skin test or in vitro reactivity to a perennial
aeroallergen
• and whose symptoms are inadequately controlled with inhaled
corticosteroids
(Corren, 2003)
Omalizumab (Xolair)
• In children with moderate to severe asthma it
reduces the rate of serious asthma exacerbations
– and the need for physician or emergency department visits
and hospitalizations
– improves asthma quality-of-life scores
• Although this new agent seems promising, its use is
likely to be limited because it has an estimated cost
of $10,000 per patient per year
– Its use may be cost-effective if limited to allergic asthmatics
who are poorly controlled on maximal therapy
– and who are hospitalized five or more times (or for 20 days
or longer) per year
(Corren, 2003)
Sublingual Immunotherapy
(SLIT)
(www.allergycapital.com, 2007)
Sublingual Immunotherapy
(SLIT)
• Improves asthma symptoms and reduces
medication use compared with placebo in
children with asthma
– Who are allergic to house dust mites and in
children with allergic rhinitis that is related to a
variety of common inhalant allergens
(Courtney, 2005)
It appears to be safe, with unwanted effects
being as low as 9.6% and no life-threatening
adverse effects reported.
Sublingual Immunotherapy
(SLIT)
• However, SLIT has not been compared
directly with standard immunotherapy
– While it is a procedure and therefore is not
regulated by the U.S. Food and Drug
Administration (FDA), the extracts used for SLIT
are FDA-approved for diagnosis and injectable
immunotherapy only
(Courtney, 2005)
• Use of FDA-approved allergic extracts for
SLIT is an off-label use
– Health insurers consider SLIT investigational
and do not cover its use
Long-Acting Beta2 Agonists
(www.asthme-queec.ce, 2007)
Long-Acting Beta2 Agonists
• Compared with placebo, salmeterol (Serevent)
produces improved lung function in children
– but there is conflicting evidence about whether it reduces
the use of rescue or short-acting beta2 agonists
• Associated with a significant increase in bronchial
hyper-reactivity compared with inhaled
corticosteroids
• Not recommended for use as monotherapy in
children with asthma
– However, limited evidence from a single three-month study
with 210 patients shows that the combination of a longacting beta2 agonist and inhaled corticosteroids may
increase the number of symptom-free days
(Simons, 1997)
Oral Theophylline
• Initially seemed promising in the prophylactic
treatment of childhood asthma
– When compared with placebo
• significantly increased the mean morning peak
expiratory flow rate
• reduced the mean number of acute nighttime attacks
and doses of bronchodilator used
• However, it proved to be less promising when
its use over one year was compared with the
use of inhaled corticosteroids
(Simons, 1997)
Oral Theophylline
• Although there was no significant difference between
theophylline and inhaled corticosteroids in reduction
of asthma symptoms
– There was an increased use of short-acting beta2 agonists
and oral corticosteroids in children receiving theophylline
In summary, its use in children cannot be
recommended because of the potential for serious
side effects, such as cardiac arrhythmias or
convulsions, if therapeutic blood levels are
exceeded.
(Simons, 1997)
Immunotherapy
• Can be used as an adjunct to standard
drug therapy in allergic asthmatic
children
• Sublingual (allergy drops) and
injectable (allergy shots) therapies
– have been shown to reduce the presence
of asthma and the overall use of asthma
medication
(Pifferi, 2002)
Immunotherapy
• Standard immunotherapy has a 1.7 to
15 % reported range of adverse effects
– between 1985 and 1989, there were 17
standard immunotherapy-related deaths
reported in the United States
Usual Dosages for Medications Used in the Long-Term
Control of Asthma in Children (part 1)
Medication
Dosage form
Dosage*
Formoterol (Foradil Aerolizer)
DPI: 12 mcg per single-use capsule
1 capsule every 12 hours
Salmeterol (Serevent)
MDI: 21 mcg per puff
1 to 2 puffs every 12 hours
DPI: 50 mcg per blister
1 blister every 12 hours
DPI: 100, 250, or 500 mcg of
fluticasone with 50 mcg of
salmeterol
1 inhalation twice daily; dosage
depends on severity of asthma
MDI: 1 mg per puff
1 to 2 puffs 3 to 4 times daily
Nebulizer solution: 20 mg per
ampule
1 ampule 3 to 4 times daily
MDI: 1.75 mg per puff
1 to 2 puffs 2 to 4 times daily
Long-acting inhaled beta2 agonists†
Combined medication
Fluticasone/salmeterol (Advair
Diskus)
Cromolyn and nedocromil
Cromolyn (Intal)
Nedocromil (Tilade)
DPI = dry-powder inhaler; MDI = metered-dose inhaler.*-Dosages are for children 12 years or younger unless otherwise specified. †-Should not be used for symptom relief or
exacerbations. Use with an inhaled corticosteroid. ‡-Serum monitoring is important (serum concentration of 5 to 15 mcg per mL at steady state). Adapted from National Asthma
Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002. Bethesda, Md.: U.S. Department of Health and
Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 2003; NIH publication no. 02-5074:133-5.
Usual Dosages for Medications Used in the Long-Term
Control of Asthma in Children (part 2)
Medication
Dosage form
Dosage*
Montelukast (Singulair)
4- or 5-mg chewable tablets, 4-mg
packet of oral granules, 10-mg
tablets
Age 12 to 23 months: 4 mg oral
granules at bedtime
Age 2 to 5 years: 4 mg at bedtime
Age 6 to 14 years: 5 mg at bedtime
Older than 14 years: 10 mg at
bedtime
Zafirlukast (Accolate)
10- and 20-mg tablets
Age 7 to 11 years: 20 mg daily in
divided
doses (i.e., one 10-mg tablet twice
daily)
12 years and older: 20 mg twice
daily
Liquids, sustained-release tablets,
and capsules
Starting dosage is 10 mg per kg per
day
Usual maximums:
Age < 1 year: (0.2 x [age in weeks])
+ 5 = mg per kg per day
Age >= 1 year: 16 mg per kg per
day
Leukotriene modifiers
Methylxanthines‡
Theophylline
DPI = dry-powder inhaler; MDI = metered-dose inhaler.*-Dosages are for children 12 years or younger unless otherwise specified. †-Should not be used for symptom relief or
exacerbations. Use with an inhaled corticosteroid. ‡-Serum monitoring is important (serum concentration of 5 to 15 mcg per mL at steady state). Adapted from National Asthma
Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002. Bethesda, Md.: U.S. Department of Health and
Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 2003; NIH publication no. 02-5074:133-5.
Estimated Comparative Daily Dosages of Inhaled
Corticosteroids in Children 12 Years and Younger
Agent
Low daily dose
Medium daily dose
High daily dose
Beclomethasone CFC
(Beclovent, Vanceril), 42
or 84 mcg per puff
84 to 336 mcg
336 to 672 mcg
> 672 mcg
Beclomethasone HFA, 40
or 80 mcg per puff
80 to 160 mcg
160 to 320 mcg
> 320 mcg
DPI: 200 mcg per
inhalation
100 to 200 mcg
200 to 400 mcg
> 400 mcg
Nebulizer solution: 0.25 or
0.5 mg per ampule
0.5 mg
1.0 mg
2.0 mg
Flunisolide (Aerobid), 250
mcg per puff
500 to 750 mcg
1,000 to 1,250 mcg
> 1,250 mcg
MDI: 44, 110, or 220 mcg
per puff
88 to 176 mcg
176 to 440 mcg
> 440 mcg
DPI: 50, 100, or 250 mcg
per inhalation
100 to 200 mcg
200 to 400 mcg
> 400 mcg
Triamcinolone acetonide
(Azmacort), 100 mcg per
puff
400 to 800 mcg
800 to 1,200 mcg
> 1,200 mcg
Budesonide (Pulmicort)
Fluticasone (Flovent)
CFC = chlorofluorocarbon; HFA = hydrofluoroalkane; DPI = dry-powder inhaler; MDI = metered-dose inhaler. Adapted from National Asthma Education and Prevention Program. Expert panel report:
guidelines for the diagnosis and management of asthma: update on selected topics, 2002. Bethesda, Md.: U.S. Department of Health and Human Services, Public Health Service, National Institutes
Key Clinical Recommendations
A spacer with a metered-dose inhaler is as effective as a nebulizer for delivery of a
bronchodilator in the treatment of an acute asthma exacerbation and for the delivery
of chronic prophylactic medications.
Physicians should consider adding inhaled ipratropium bromide (Atrovent) with each
inhalation of a beta2 agonist, particularly in the treatment of a more severe asthma
exacerbation.
If possible, oral corticosteroids should be administered within 45 minutes of the onset
of symptoms in an acute asthma exacerbation.
Modest doses of an inhaled corticosteroid are more effective than inhaled long-acting
beta2 agonists, inhaled nedocromil (Tilade), and leukotriene inhibitors in improving
asthma symptoms and lung function in children with moderate persistent asthma and
are recommended as the first-line treatment.
Parents and caregivers of children with asthma, particularly those with moderate to
severe disease, should be taught to recognize and avoid triggers and to understand
the use of prescribed medications and inhalation devices, and the importance of
compliance and monitoring.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, opinion, or case series.
Adapted from National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002. Bethesda, Md.:
U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 2003. NIH publication no. 02-5074:135.
Let’s Review!
Management of severe persistent asthma
might include:
A.
B.
C.
D.
E.
Long-acting beta2 agonist
High dose inhaled corticosteroid
Leukotriene modifier
Anticholinergic inhaler
All of the above