Airway hyperresponsiveness in children with sickle cell anemia.
BACKGROUND
The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.


METHODS
To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS.


RESULTS
Methacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1<4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P<.001), IgE (P=.009), and lactate dehydrogenase (LDH) levels (P=.005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P=.986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction.


CONCLUSIONS
In children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.
Field
Joshua J
JJ
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Stocks
Janet
J
Portex Respiratory Unit, University College London, Institute of Child Health, London, England.
Kirkham
Fenella J
FJ
Neurosciences Unit, University College London, Institute of Child Health, London, England.
Rosen
Carol L
CL
Department of Pediatrics, Case School of Medicine, Cleveland, OH.
Dietzen
Dennis J
DJ
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Semon
Trisha
T
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Kirkby
Jane
J
Portex Respiratory Unit, University College London, Institute of Child Health, London, England.
Bates
Pamela
P
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Seicean
Sinziana
S
Department of Epidemiology and Biostatistics, Case School of Medicine, Cleveland, OH.
DeBaun
Michael R
MR
Departments of Pediatrics, Neurology and Biostatistics, Washington University School of Medicine, St. Louis, MO.
Redline
Susan
S
Department of Pediatrics, Case School of Medicine, Cleveland, OH.
Strunk
Robert C
RC
Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: strunk@kids.wustl.edu.
D000280:Administration, Inhalation; D000293:Adolescent; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000150:complications*; D001249:Asthma / Q000453:epidemiology* / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016014:Linear Models; D008168:Lung / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000009:adverse effects*; D015995:Prevalence; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012307:Risk Factors; D055815:Young Adult
D016210:Methacholine Chloride; D007073:Immunoglobulin E; D007770:L-Lactate Dehydrogenase