Reduced forced expiratory flow but not increased exhaled nitric oxide or airway responsiveness to methacholine characterises paediatric sickle cell airway disease

Thorax. 2014 Jun;69(6):580-5. doi: 10.1136/thoraxjnl-2013-204464. Epub 2014 Feb 12.


Background: Asthma and airway hyper-responsiveness are reportedly more common in children with sickle cell disease (SCD).

Aim: To determine airway responsiveness, airway inflammation and clinical features of asthma in SCD.

Methods: A prospective, single-centre study of 50 SCD children without overt pulmonary vascular disease and 50 controls. Exhaled nitric oxide (FeNO) and total serum IgE were measured and spirometry and methacholine challenge were performed. The methacholine dose-response slope (DRS) was calculated.

Results: Doctor diagnosis of asthma was made in 7 (14%) SCD versus 12 (24%) control subjects (p=0.203). FeNO levels were similar in SCD and controls (p=0.250), and were higher in those with atopy and an asthma diagnosis (OR 4.33, 95% CI 1.7 to 11.1; p<0.05). zFEV1 (p=0.002) and zFEV1/FVC (p=0.003) but not zFVC (p=0.098) were lower in SCD versus controls. DRS was higher in those with asthma (p=0.006) but not in SCD versus controls (p=0.403). DRS correlated with FeNO and blood eosinophil count in controls but not SCD. In SCD, DRS was higher in those admitted to hospital with respiratory symptoms (n=27) versus those never admitted (n=23) (p=0.046). DRS was similar in those with at least one acute chest syndrome episode (n=12) versus those with none (n=35) (p=0.247).

Conclusions: SCD children have airflow obstruction despite having minimal evidence of pulmonary vascular disease. Airflow obstruction is not associated with increased methacholine sensitivity or eosinophilic inflammation, at least as judged by FeNO. Airflow obstruction in SCD does not appear to be related to childhood eosinophilic asthma, but its pathophysiology remains ill understood.

Keywords: Paediatric lung disease; airway hyper-responsiveness; airway obstruction; sickle cell disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Airway Obstruction / metabolism
  • Airway Obstruction / physiopathology
  • Anemia, Sickle Cell / metabolism
  • Anemia, Sickle Cell / physiopathology*
  • Asthma / diagnosis
  • Asthma / metabolism
  • Asthma / physiopathology*
  • Breath Tests
  • Case-Control Studies
  • Child
  • Eosinophils
  • Female
  • Forced Expiratory Flow Rates / physiology*
  • Humans
  • Hypersensitivity / metabolism
  • Hypersensitivity / physiopathology
  • Immunoglobulin E / blood*
  • Leukocyte Count
  • Lung / blood supply
  • Male
  • Methacholine Chloride*
  • Nitric Oxide / analysis*
  • Nitric Oxide / metabolism
  • Spirometry
  • Statistics, Nonparametric


  • Methacholine Chloride
  • Nitric Oxide
  • Immunoglobulin E