Airway hyperresponsiveness in children with sickle cell anemia

Chest. 2011 Mar;139(3):563-568. doi: 10.1378/chest.10-1243. Epub 2010 Aug 19.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Age Factors
  • Anemia, Sickle Cell / complications*
  • Asthma / epidemiology*
  • Asthma / physiopathology*
  • Bronchial Provocation Tests
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Immunoglobulin E / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Linear Models
  • Lung / physiopathology
  • Male
  • Methacholine Chloride / administration & dosage
  • Methacholine Chloride / adverse effects*
  • Prevalence
  • Prospective Studies
  • Respiratory Function Tests
  • Risk Factors
  • Young Adult


  • Methacholine Chloride
  • Immunoglobulin E
  • L-Lactate Dehydrogenase