Asthma as a Modifier of Sickle Cell Disease Severity

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Asthma as a Modifier of Sickle Cell Disease
Severity

• Joshua Field
• Division of Hematology
• March 6, 2009

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Disclosure Joshua Field, M.D.
Joshua Field, M.D. has financial interests to
disclose. Potential conflicts of interest have
been resolved.

• Research Support / Grants TRF pharma
• Stock/Equity (any amount) none
• Consulting / Employment none
• Speakers Bureau / Honoraria none
• Other none

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Overview

• Case
• Asthma and sickle cell disease morbidity and
  mortality
• Relationship to clinical characteristics of
  asthma
• Potential mechanism for asthma increasing
  vaso-occlusion
• Conclusions

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Case

• 17 year-old man with HbSS
• Diagnosed with asthma at age 6 years
• Last 3 years 10 hospital admissions for pain
• Medications include
• Albuterol
• Family history mother has asthma
• Laboratory data
• WBC 13.3
• Hemoglobin 6.9
• IgE 1870 IU/ml (gt250 IU/ml)

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Case

• Numerous positive allergy skin tests
• PFTs
• FEV1 98
• FEV1/FVC 74 (lt80)
• Bronchodilator response 14.65 (gt12)
• Exhaled nitric oxide 63.3 ppb (gt15 ppb)
• Methacholine challenge pc20 0.26 mg/ml (lt8 mg/ml)

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Asthma and SCA morbidity

• Hypothesis A doctor diagnosis of asthma is
  associated with an increased rate of
  hospitalization for pain in children with SCA
• Design Prospective cohort study (Cooperative
  Study of Sickle Cell Disease)
• Results
• Infant cohort n291
• Follow-up mean 11 years
• 17 diagnosed with asthma

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Boyd, et al. Blood, 2006
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Asthma and SCA mortality

• Hypothesis A doctor diagnosis of asthma is
  associated with increased mortality
• Design Prospective cohort study (Cooperative
  Study of Sickle Cell Disease)
• Results
• 1,963 children and adults with SCA (138 diagnosis
  of asthma, 1,825 controls)

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Boyd, et al. Haematologica, 2007
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Adult SCD Clinic at Washington University
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Asthma in individuals with Sickle Cell Disease

• Doctor diagnosis of asthma is associated with
  increased morbidity
• What does doctor diagnosis of asthma mean in an
  individual with SCD?

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

• Definition of asthma includes
• Airway inflammation (eNO)
• Many have other atopic conditions (allergy skin
  tests)
• Airway obstruction with reversibility (PFTs)
• Presence of airway hyper responsiveness
  (methacholine)

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Asthma relationships among children
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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Airway Hyper Responsiveness (AHR) and SCA

• Hypothesis AHR is associated with a diagnosis of
  asthma and clinical characteristics of asthma in
  children with SCA
• Design Prospective Cohort Study (multi-center
  Sleep and Asthma Cohort Study)

Field, et al, submitted.
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AHR and SCA

• Results
• 70 children
• 54 had hyper responsiveness (PC20lt8mg/ml)
• PC20 correlated with age (plt0.001)
• After adjustment for age
• Correlated with IgE (plt0.001), BD response
  (p0.024)
• No correlations with eNO, positive allergy tests
• No correlations with
• Symptoms consistent with asthma
• Reported use of medication prescribed for asthma
• MD Dx of asthma
• At very low PC20 (lt2mg/ml), 57 had a Dx
• With a negative PC20 (gt25mg/ml), 42 had a Dx

Field, et al. submitted.
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Family History Asthma and SCA

• Hypothesis Family history of asthma, independent
  of a personal history of asthma, is associated
  with an increased rate of pain.
• Design Prospective cohort study (Cooperative
  Study of Sickle Cell Disease)
• Results
• 211 children with SCA and family, personal
  history of asthma

Field, et al. Am J Hematol, 2008
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Family history of asthma and pain
Field, et al. Am J Hematol, 2008
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Are mediators of asthma in the general population
contributing to SCA-related morbidity?
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Cysteinyl leukotrienes
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Cysteinyl leukotrienes and asthma

• Levels of cysteinyl leukotrienes are related to
• Asthma severity
• Exacerbations
• Exercise-induced bronchoconstriction

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Knight-Perry, et al. Expert Reviews in
Hematology, 2009
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Do Cysteinyl Leukotrienes contribute to
SCD-related morbidity?
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CysLTs and SCD

• Hypotheses
• Cysteinyl leukotrienes are elevated in adults
  with SCD compared to controls.
• Baseline levels of cysteinyl leukotrienes are
  related to pain rate.
• Design Prospective cohort study of adults at
  WashU(retrospective pain and acute chest syndrome
  data)
• Results
• 57 adults with SCD and 17 age, race and
  asthma-matched controls

Field, et al. Am J Hematol, 2009
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Field, et al. Am J Hematol, 2009
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CysLTs and pain
Field, et al. Am J Hematol, 2009
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CysLTs and asthma symptoms
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CysLTs and acute pain

• Hypotheses
• Cysteinyl leukotrienes increase during a pain
  episode
• Degree of cysteinyl leukotriene increase related
  to pain rate
• Design Prospective cohort study of children and
  adults at Washington University
• Results
• 19 children and adults with SCD who had baseline
  and pain measurements of cysteinyl leukotrienes

Field, et al. Am J Hematol, 2009
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Field, et al. Am J Hematol, 2009
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Field, et al. Am J Hematol, 2009
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Case

• Evaluated by pulmonolgy
• Initiated on inhaled corticosteroids
• Received asthma education
• Asthma action plan
• Aggressively treated exacerbations
• No hospital admissions for pain in past year

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Conclusions

• Asthma is a significant modifier of disease
  severity
• Clinical characteristics different than in
  general population
• Reasonable to pursue asthma evaluations and
  potentially initiate asthma therapies

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Acknowledgements

• Michael DeBaun
• Robert Strunk
• Morey Blinder