Sickle Cell Disease How Does It Interact With Asthma

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Sickle Cell Disease How Does It Interact With
Asthma?
R. Strunk, M. DeBaun, J. Field
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Goals of Presentation

• Present case from our clinic implicating the role
  of asthma in SCD outcomes
• Review studies demonstrating impact of a doctor
  diagnosis of asthma on SCD outcomes
• Review characteristics of asthma in children with
  SCD, compared to children without SCD

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How do we think about the pathophysioligy of
asthma in a child without SCD?

• Definition of asthma includes
• Airway inflammation (exhaled nitric oxide)
• Most children are allergic (allergy skin tests)
• Many have other atopic conditions (e.g., eczema)
• Variable clinical course with response to
  therapy
• Airway obstruction with reversibility
• Presence of airway hyper responsiveness
• (positive methacholine challenge, or PC20)
• Positive family history (mother best marker)

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Kato, NHLBI
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Clinical Observation

• 11 year old male presents to SCD clinic with
  complaint of diffuse pain for three weeks with no
  relief after Oxycontin at home
• Meds Folic Acid, Hydroxyurea and Albuterol
• PE
• Tender with palpation to back, chest, extremities
• Chest exam - no wheeze

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• Asthma is Associated with Acute Chest Syndrome
  and Pain in Children
• with Sickle Cell Anemia
• Boyd J, Macklin E, Strunk R and DeBaun M
• Blood 2006108(9)2923-7

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Results

• 257 children enrolled in the birth cohort of
  Cooperative Study of Sickle Cell Disease (CSSCD)
  met study criteria
• Mean follow-up
• 12.3 years
• Asthma
• 18 (46/257)

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Asthma is Associated with Pain in Children with
Sickle Cell Anemia
(plt0.001)
Blood 2006108(9)2923-7
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Asthma is Associated with ACS in Children with
Sickle Cell Anemia
(plt0.001)
Blood 2006108(9)2923-7
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Need for confirmation of findings from
independently obtained data
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Asthma in Sickle Cell Disease as a Risk Factor
for Acute Chest Syndrome and Pneumonia in
Pediatric Patients

• Borns A, Marquez K, Amendah D, Whiteman A, Jordan
  L, Grant A

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• MarketScan Multi-State Medicaid Database
  collected demographic information as well as
  procedure and diagnosis claims
• ICD-9-CM codes were used to identify SCD, ACS,
  asthma, and pneumonia
• Children who had at least one admission in 2005
  with SCD listed as a discharge diagnosis or those
  who had at least two outpatient encounters at
  least 30 days apart
• Children with asthma were defined with similar
  criteria
• The incidence of pneumonia among children with
  SCD, since ACS is a pneumonia-like disease that
  could potentially be misdiagnosed as pneumonia

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Frequency of Acute Chest Syndrome and Pneumonia
by Asthma Group n 2428
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What might be the mechanism by which asthma
worsens outcomes of SCD?
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Adapted from Setty et al. Blood.1999 Sep
194(5)1555-60
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Histopathology of Experimentally Induced Asthma
in a Murine Model of Sickle Cell Disease

• Nandedkar S, Feroah T, Hutchins W, Weihrauch D,
  Konduri K, Wang J, Strunk R, DeBaun M,
• Hillery C and Pritchard K
• Blood 2008112(6)2529-38

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Proof of Principle A SCD Mouse with
Experimental Asthma
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Transgenic SCD Model with Asthma
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Survival of SCD Mice After OVA Sensitization
100
95
90
85
Hb A Unsensitized
Hb A Sensitized Low
Survival
Hb A Sensitized Normal
SCD Unsensitized
80
SCD Sensitized Low
SCD Sensitized Normal
75
70
65
60
0
5
10
15
Days after Start of Aerosolization
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Asthma in Children with Sickle Cell Disease

• MD Dx is associated with increased morbidity
• What does MD Dx of asthma mean in a child with
  SCD?

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How do we think about a diagnosis of asthma in a
child without SCD?

• Definition of asthma includes
• Airway inflammation (exhaled nitric oxide)
• Most children are allergic (allergy skin tests)
• Many have other atopic conditions (e.g., eczema)
• Variable clinical course with response to
  therapy
• Airway obstruction with reversibility
• Presence of airway hyper responsiveness
• (positive methacholine challenge, or PC20)
• Positive family history (mother best marker)

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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
For children with out SCD all boxes connect to
asthma diagnosis
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Sleep and Asthma Cohort (SAC n 240)

• Children with SCA (HbSS)
• Evaluation of asthma characertistics
  systematically

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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
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Asthma relationships
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx
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Asthma relationships among children With SCD
FH, assoc atopic conditions
airway obst, BD response, AST, IgE
eNO
PC20
Asthma Diagnosis
Symptoms
Risk of pain/ACS
FH family history Airway obstruction on
spirometry BD bronchodilator AST allergy skin
testing IgE total serum PC20 result of
methacholine challenge eNO exhaled nitric oxide
response to Tx ??
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Comparison of SAC Asthma to Asthma in African
American Children with Asthma in the Childhhood
Asthma Management Program (CAMP)
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ATS/DLD Questionniare
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Summary of what we have learned about asthma in
SCD

• Asthma-like symptoms occur frequently and appear
  to be the basis of a doctor making a diagnosis of
  asthma
• Some features of asthma (e.g., bronchodilator
  response) are present in children with SCD and
  are associated with a Dx of asthma