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Original Research: ASTHMA |

Airway Hyperresponsiveness in Children With Sickle Cell Anemia

Joshua J. Field, MD; Janet Stocks, PhD; Fenella J. Kirkham, MD; Carol L. Rosen, MD; Dennis J. Dietzen, PhD; Trisha Semon, MS, CPFT; Jane Kirkby, BSc, ARTP; Pamela Bates, CRT, RPFT; Sinziana Seicean, MD, MPH; Michael R. DeBaun, MD, MPH; Susan Redline, MD; Robert C. Strunk, MD
Author and Funding Information

From the Department of Medicine (Dr Field), the Department of Pediatrics (Dr Dietzen and Mss Semon and Bates), the Departments of Pediatrics, Neurology and Biostatistics (Dr DeBaun), and the Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics (Dr Strunk), Washington University School of Medicine, St. Louis, MO; the Portex Respiratory Unit (Dr Stocks and Ms Kirkby), and the Neurosciences Unit (Dr Kirkham), University College London, Institute of Child Health, London, England; and the Department of Pediatrics (Drs Rosen and Redline), and the Department of Epidemiology and Biostatistics (Dr Seicean), Case School of Medicine, Cleveland, OH.

Correspondence to: Robert C. Strunk, MD, Division of Allergy and Immunology, Department of Pediatrics, Box 8116, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110; e-mail: strunk@kids.wustl.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Funding/Support: This study was supported by the National Heart, Lung, and Blood Institute [Grants R01 HL079937 to Drs Stocks, Kirkham, Rosen, DeBaun, Redline, and Strunk and K12 HL08710 to Dr Field].


© 2011 American College of Chest Physicians


Chest. 2011;139(3):563-568. doi:10.1378/chest.10-1243
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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.

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