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Asthma as a Modifier of Sickle Cell Disease Severity

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Title: Asthma as a Modifier of Sickle Cell Disease Severity


1
Asthma as a Modifier of Sickle Cell Disease
Severity
  • Joshua Field
  • Division of Hematology
  • March 6, 2009

2
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

3
Overview
  • Case
  • Asthma and sickle cell disease morbidity and
    mortality
  • Relationship to clinical characteristics of
    asthma
  • Potential mechanism for asthma increasing
    vaso-occlusion
  • Conclusions

4
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)

5
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)

6
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

7
Boyd, et al. Blood, 2006
8
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)

9
Boyd, et al. Haematologica, 2007
10
Adult SCD Clinic at Washington University
11
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?

12
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)

13
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
14
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.
15
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.
16
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
17
Family history of asthma and pain
Field, et al. Am J Hematol, 2008
18
Are mediators of asthma in the general population
contributing to SCA-related morbidity?
19
Cysteinyl leukotrienes
20
Cysteinyl leukotrienes and asthma
  • Levels of cysteinyl leukotrienes are related to
  • Asthma severity
  • Exacerbations
  • Exercise-induced bronchoconstriction

21
Knight-Perry, et al. Expert Reviews in
Hematology, 2009
22
Do Cysteinyl Leukotrienes contribute to
SCD-related morbidity?
23
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
24
Field, et al. Am J Hematol, 2009
25
CysLTs and pain
Field, et al. Am J Hematol, 2009
26
CysLTs and asthma symptoms
27
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
28
Field, et al. Am J Hematol, 2009
29
Field, et al. Am J Hematol, 2009
30
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

31
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

32
Acknowledgements
  • Michael DeBaun
  • Robert Strunk
  • Morey Blinder
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