Diagnosing and Management of Asthma in Children Four years and Younger

1
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 Childrens Hospital at Stanford

2
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

3
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-ve
rsus-asthmatic-bronchiole.html
4
Asthmatic Inflammation
Subacute/Chronic Inflammation
Late Asthmatic Response
Early Asthmatic Response
Normal Airway
Inhaled trigger
chemotactic factors cytokines
Recruitment and activation of inflammatory cells
Neural vascular effects
Mast Cells Alveolar macrophages
5
                                                
                                                  
  Figure 2. Inflammatory and remodelling
responses in asthma with activation of the
epithelial mesenchymal trophic unit
Lancet, Vol 368, 2006-1 September 2006, Pages
780-793
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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

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Potential Risk Factors1

• Host factors
• Genetic predisposition
• Atopy
• Airway hyperresponsiveness
• Gender
• Race/Ethnicity
• Environmental factors
• Indoor allergens
• Outdoor allergens
• Occupational sensitizer

• Environmental factors (cont)
• Tobacco smoke
• Air pollution
• Respiratory infections
• Socioeconomic status
• Family size
• Diet and drugs
• Obesity

1Masoli M, et al. The Global Burden of Asthma
Executive Summary of the GINA Dissemination
Committee Report. Allergy 2004 59 469-78.
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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

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Differential Diagnosis Wheezing

• Asthma
• Congenital Anomalies with airway impingement
  Vascular 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

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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).

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Diagnosing Asthma in Young Children Asthma
Predictive Index

• gt 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 (gt4)
• Wheezing apart from colds

1Adapted from Castro-Rodriquez JA, et al. AJRCCM
2000 162 1403
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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)

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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

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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 gt4 exacerbations/year, 2
  episodes of oral steroids in 6 months, or use of
  SABAs (albuterol) more then twice a week

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Steps of Therapy 0-4 Years

• Step 1 intermittent- use SABA prn
• Step 2 mild persistent-use low dose ICS OR
  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)

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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!

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Inhaled Corticosteroid

• Preferred treatment alone or in combination 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 remodelingProbably no longer
  true

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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
1.6
Pooled Relative Risk
-15
-10
-5
0
5
10
15
10
0.1
1
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
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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. 19851997
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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)

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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/asthma-common-as
thma-triggers.html
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Tailored Environmental Intervention

• Morgan et al, 20041
• Randomized, controlled trial of environmental
  intervention
• Intervention resulted in
• Reduction in asthma symptoms, disruption in
  caretakers plans, caretakers and childs 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.
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A Potential Gap inPatient-Provider
CommunicationsAsthma Practices- Two
Perspectives Patients and Doctors1
Patient Doctor
97
92
90
83
70
70
55
35
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Base All patients (unweighted N2509), all
doctors (unweighted N512).
1Adapted from http//www.asthmainamerica.com/slide
s/powerpoint/slide27.ppt
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Neuroendocrine Mechanisms-Stress and Asthma

• Common clinical observations of adverse
  relationship 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.
  200493S11-S17

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Asthma Goals of Treatment1

• 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.
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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

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Hypothetical representation of 2 separate
developmental pathways present in persistent
asthma
Martinez, F, JACI, 11930-33, January 2007
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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.

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Thats Enough!
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