title: Airway hyperresponsiveness in children with sickle cell anemia.
abstract: 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.
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: Joshua J
authors: JJ
authors: Field
authors: Portex Respiratory Unit, University College London, Institute of Child Health, London, England.
authors: Janet
authors: J
authors: Stocks
authors: Neurosciences Unit, University College London, Institute of Child Health, London, England.
authors: Fenella J
authors: FJ
authors: Kirkham
authors: Department of Pediatrics, Case School of Medicine, Cleveland, OH.
authors: Carol L
authors: CL
authors: Rosen
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors: Dennis J
authors: DJ
authors: Dietzen
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors: Trisha
authors: T
authors: Semon
authors: Portex Respiratory Unit, University College London, Institute of Child Health, London, England.
authors: Jane
authors: J
authors: Kirkby
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors: Pamela
authors: P
authors: Bates
authors: Department of Epidemiology and Biostatistics, Case School of Medicine, Cleveland, OH.
authors: Sinziana
authors: S
authors: Seicean
authors: Departments of Pediatrics, Neurology and Biostatistics, Washington University School of Medicine, St. Louis, MO.
authors: Michael R
authors: MR
authors: DeBaun
authors: Department of Pediatrics, Case School of Medicine, Cleveland, OH.
authors: Susan
authors: S
authors: Redline
authors: Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: strunk@kids.wustl.edu.
authors: Robert C
authors: RC
authors: Strunk
mesh_terms: 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
chemical_list: D016210:Methacholine Chloride; D007073:Immunoglobulin E; D007770:L-Lactate Dehydrogenase