Transcript Controversies in Asthma Care in Children

Diagnosing and Management of
Asthma in Children Four years
and Younger
John D. Mark MD
Clinical Assoc Professor of Pediatrics
Pediatric Pulmonary Medicine
Lucile Packard Children’s Hospital at Stanford
Objectives
• To better understand how to differentiate between
infants who wheeze and go on to develop asthma
and those who wheeze but do not go on to have
asthma
• To discuss management strategies for treating
children with a high risk of developing asthma
• To discuss possible prevention therapies for
asthma in children four years old or younger
What is Asthma?
• Disease of chronic
inflammatory disorder of the
airways
• Characterized by
• Airway inflammation
• Airflow obstruction
• Airway
hyperresponsiveness
Cookson W. Nature 1999; 402S: B5-11
http://health.allrefer.com/health/asthma-normal-versus-asthmatic-bronchiole.html
Asthmatic Inflammation
Normal
Airway
Early Asthmatic
Response
Late Asthmatic
Response
Subacute/Chronic
Inflammation
Inhaled trigger
chemotactic factors
cytokines
Mast Cells
Alveolar macrophages
Recruitment and
activation of
inflammatory cells
Neural &
vascular
effects
Figure 2. Inflammatory and remodelling responses in asthma with activation of the
epithelial mesenchymal trophic unit
What Causes Asthma?
• Asthma is a complex trait
• Heritable and environmental factors contribute
to its pathogenesis. Viral infections appears
have an expanding role as well.
• Onset appears early in life and severity remains
constant
• Multiple interacting genes
• At least 20 distinct chromosomal regions with
linkage to asthma and asthma related traits have
been identified: Chromosome 5q , ADAM33 ,
PHF11
Potential Risk Factors1
• Host factors
• Genetic predisposition
• Atopy
• Airway
hyperresponsiveness
• Gender
• Race/Ethnicity
• Environmental factors
• Indoor allergens
• Outdoor allergens
• Occupational sensitizer
1Masoli
• Environmental factors (cont)
• Tobacco smoke
• Air pollution
• Respiratory infections
• Socioeconomic status
• Family size
• Diet and drugs
• Obesity
M, et al. The Global Burden of Asthma: Executive Summary of the GINA
Dissemination Committee Report. Allergy 2004; 59: 469-78.
Diagnosing Asthma-Not Easy
• Clinical diagnosis supported by the certain
historical, physical and laboratory findings
• History of episodic symptoms of airflow
obstruction (e.g.. breathlessness, wheezing,
and COUGH)-response to therapy!
• Physical: wheeze, hyperinflation
• Laboratory: exhaled nitric oxide (eNO),
spirometry
• Exclude other possibilities
Differential Diagnosis Wheezing
• Asthma
• Congenital Anomalies with airway impingement: Vascular
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rings, tracheobronchial obstruction, mediastinal mass
Bronchopulmonary dysplasia
Cystic fibrosis
Gastroesophageal reflux
Aspiration
Foreign Body Aspiration
Heart Failure
Sinusitis and allergic rhinitis
Bronchiolitis
Pertussis
Tuberculosis
Immune system Disorders
Wheezing in Infants
• Group 1: Low Lung function: children improve
within a few years and "outgrow" their asthma
• Group 2: Non-Atopic, viral-induced asthma:
also outgrow asthma after a somewhat longer
period of time (nonatopic wheezing).
• Group 3: Atopic Asthma: in contrast, children
who will go on to develop persistent wheezing
beyond infancy and early childhood usually
have a family history of asthma and allergies
and present with allergic symptoms very early
in life (atopy-associated asthma).
Diagnosing Asthma in Young Children
– Asthma Predictive Index
• > 4 episodes/yr of
wheezing lasting more
than 1 day affecting
sleep in a child with
one MAJOR or two
MINOR criteria
• Major criteria
• Parent with asthma
• Physician diagnosed
atopic dermatitis
• Minor criteria
• Physician diagnosed
allergic rhinitis
• Eosinophilia (>4%)
• Wheezing apart from
colds
1Adapted
from Castro-Rodriquez JA, et al. AJRCCM 2000; 162: 1403
Asthma Diagnosis Made
• Identify precipitating factors (pets, ETS,
mold)
• Identify comorbid conditions that may
aggravate asthma (GERD, allergies etc)
• Assess the patient/families knowledge and
self management skills
• Classify asthma severity using the
Guidelines from the NHLBI (Expert Panel)
Assessing Asthma Severity
• Use Impairment and Risk
• Impairment
• Symptoms: night time symptoms, reliever use
(SABA), miss school/work, quality of life, ACT
screen
• Lung function- spirometry (FEV0.5), eNO
• Risk
• Recurrent exacerbations including ED visits and
hospitalization (may be normal between events)
• At times, hard to differential between impairment
and risk
Classifying Asthma Severity in
Children 0-4 Years of Age
• Break down into intermittent, mild, moderate,
or severe persistent asthma depending on
symptoms of impairment and risk
• Once classified, use the 6 steps depending on
the severity to obtain asthma control with the
lowest amount of medication
• Controller medications (inhaled steroids)
should be considered if >4 exacerbations/year, 2
episodes of oral steroids in 6 months, or use of
SABA’s (albuterol) more then twice a week
Steps of Therapy 0-4 Years
• Step 1: intermittent- use SABA prn
• Step 2: mild persistent-use low dose ICS OR
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montelukast OR cromolyn alternatives
Step 3: moderate persistent: moderate dose of
ICS
Step 4: moderate persistent: moderate dose of
ICS and add either montelukast or LABA
Step 5: severe persistent: high dose ICS and
montelukast or LABA
Step 6: severe persistent: high dose ICS and
montelukast or LABA plus oral steroids
Consult asthma specialist if step 3 or higher
(consider at step 2)
Maintaining Control
• Monitor carefully- every 6 months if stable,
more often if not
• If stable after 3 months, try to reduce therapy
(usually by 25-50%)
• Inhaled steroids are safe even in the young at
mild to moderate doses with only a slight
decrease in growth velocity. Higher doses have
been shown to affect growth, cause cataracts
and reduce bone density
• Response to therapy is very important in this
age group!
Inhaled Corticosteroid
• Preferred treatment alone or in combination
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for all persistent categories of asthma
Safe when use is monitored
Reduces asthma symptoms, bronchial
hyperreactivity, exacerbations and
hospitalizations, need for rescue
medications
Improves lung function, quality of life
May prevent airway remodeling…Probably
no longer true
ICS Are More Effective at Decreasing Asthma
Exacerbations Than Anti-leukotriene Agents
Maspero
Baumgartner
Busse
Hughes (BUD)*
Hughes (FP)
Laviolette*
Skalky
Williams
Bleecker
Busse
Kim
Fixed Effects
Pooled Relative Risk
1.6
0.1 -15
-10
-5
0
1
+5
+10
+15
+10
Relative Risk (95% CI)
Favors anti-leukotrienes
Favors inhaled glucocorticoids
Results not affected by type of medication, methods, analysis, publication
status or funding source. Insufficient evidence in children.
* No exacerbations reported
Ducharme FM, BMJ 2003; 326: 621
Role of ICS in Asthma
• Trials show that among children with asthma (or at risk for
asthma), controller therapy with ICS is efficacious in
controlling asthma symptoms
• However, ICS, do not change the natural clinical course of
the disease.
• PEAK trial 285 children aged 2 to 3 years at high risk for
asthma were randomized to therapy with either an ICS
(fluticasone, 88 μg twice daily for 2 years) or placebo
• Results showed significantly better clinical outcomes and
lung function outcomes in children treated with fluticasone
than in those treated with placebo
• However, clinical differences between groups rapidly
disappeared a few weeks after discontinuation of regular
treatments.
Guilbert et al. Long-term inhaled corticosteroids in preschool children at high risk
for asthma, N Engl J Med 354 (2006), pp. 1985–1997
FDA Approved Therapies
• ICS budesonide nebulizer solution (1-8 years)
• ICS fluticasone DPI (4 years of age and older)
• LABA and LABA/ICS combination DPI and MDI
(4 years of age and older)
• Montelukast chewables (2-4 years), granules
(down to 1 year of age)
• Cromolyn sodium nebulizer (2 years and older)
Is Environmental Control Helpful?
• Single allergen reduction not
effective
• “…Treatment by means of
allergen avoidance requires the
definition of what patients are
allergic to, and additional
measures beyond the use of
mattress covers and education”
Thomas Platts-Mills
http://health.allrefer.com/health/asthm
a-common-asthma-triggers.html
Tailored Environmental
Intervention
• Morgan et al, 20041
• Randomized, controlled trial of environmental
intervention
• Intervention resulted in
• Reduction in asthma symptoms, disruption in
caretakers plans, caretaker’s and child’s sleep,
asthma-related visits to the ER or clinic
• Reduction in asthma symptoms were correlated to
reduction in allergens
• No difference in reduction of allergens in
homes with carpets or without carpets
1Morgan
WJ, et al. N Engl J Med 2004; 351: 1068-80.
A Potential Gap in
Patient-Provider Communications
Asthma Practices- Two Perspectives: Patients and
Doctors1
Patient
Doctor
92%
83%
70%
70%
55%
35%
27%
28%
Base: All patients (unweighted N=2509), all doctors (unweighted N=512).
1Adapted
from http://www.asthmainamerica.com/slides/powerpoint/slide27.ppt
97%
90%
Neuroendocrine MechanismsStress and Asthma
• Common clinical observations of adverse relationship
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between stress and human disease
Adverse effects of psychological stress on asthma have
been documented.
Depression and stress can augment humoral immunity and
favor production of IgE
Immunological changes may shift from TH1 to TH2 and
promote allergic responses
Growing set of data provide evidence for association
between chronic psychological stress and the pathogenesis
of atopy and asthma
• Marshall G, Ann Allergy Asthma Immunol. 2004;93:S11-S17
Asthma: Goals of Treatment1
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Control chronic and nocturnal symptoms
Maintain normal activity levels and exercise
Maintain near-normal pulmonary function
Prevent acute episodes of asthma
Minimize emergency department (ED)
visits and hospitalizations
• Avoid adverse effects of asthma medications
1Global
Initiative for Asthma. GINA workshop report: global strategy for asthma
management and prevention. Available at: http://www.ginasthma.org. Accessed
October 13, 2006.
Asthma Prevention
• There has been remarkable progress in
pharmacotherapy, education and environmental
measures in treating asthma
• However, no single action has been demonstrated
to decrease the risk of developing asthma
• Genetic and environmental influences-key!
• Exposure to microbial products- Hygiene?
• Low level of lung function present in preschoolers with
asthma
• Prevention will depend on factors influencing the
development and progression of asthma
Hypothetical representation of 2 separate developmental pathways present in
persistent asthma
Martinez, F, JACI, 119:30-33, January 2007
Next Steps
• There is a need to develop therapeutic modalities that,
initiated even earlier in life and before the development of
the first asthma-like symptoms, will prevent progression
along the pathways to airway dysfunction.
• If a group of children with asthma in whom the disease is
confirmed, early genetic and phenotypic markers are
needed to target them for the development of specific
therapies that will thwart that progression.
• It is essential to determine whether in children with mild
persistent asthma, whether intermittent, symptom-triggered
anti-inflammatory therapy might be as effective as daily
continuous therapy with controller medications in
decreasing exacerbations and improving quality of life.
That’s Enough!