Title: Asthma as a Modifier of Sickle Cell Disease Severity
1Asthma as a Modifier of Sickle Cell Disease
Severity
- Joshua Field
- Division of Hematology
- March 6, 2009
2Disclosure 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
3Overview
- Case
- Asthma and sickle cell disease morbidity and
mortality - Relationship to clinical characteristics of
asthma - Potential mechanism for asthma increasing
vaso-occlusion - Conclusions
4Case
- 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)
5Case
- 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)
6Asthma 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
7Boyd, et al. Blood, 2006
8Asthma 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)
9Boyd, et al. Haematologica, 2007
10Adult SCD Clinic at Washington University
11Asthma 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?
12How 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)
13Asthma 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
14Airway 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.
15AHR 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.
16Family 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
17Family history of asthma and pain
Field, et al. Am J Hematol, 2008
18Are mediators of asthma in the general population
contributing to SCA-related morbidity?
19Cysteinyl leukotrienes
20Cysteinyl leukotrienes and asthma
- Levels of cysteinyl leukotrienes are related to
- Asthma severity
- Exacerbations
- Exercise-induced bronchoconstriction
21Knight-Perry, et al. Expert Reviews in
Hematology, 2009
22Do Cysteinyl Leukotrienes contribute to
SCD-related morbidity?
23CysLTs 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
24Field, et al. Am J Hematol, 2009
25CysLTs and pain
Field, et al. Am J Hematol, 2009
26CysLTs and asthma symptoms
27CysLTs 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
28Field, et al. Am J Hematol, 2009
29Field, et al. Am J Hematol, 2009
30Case
- Evaluated by pulmonolgy
- Initiated on inhaled corticosteroids
- Received asthma education
- Asthma action plan
- Aggressively treated exacerbations
- No hospital admissions for pain in past year
31Conclusions
- 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
32Acknowledgements
- Michael DeBaun
- Robert Strunk
- Morey Blinder