Asthma management: reinventing the wheel in sickle cell disease

Am J Hematol. 2009 Apr;84(4):234-41. doi: 10.1002/ajh.21359.

Abstract

Asthma is a common comorbidity in sickle cell disease (SCD) with a reported prevalence of 30-70%. The high frequency of asthma in this population cannot be attributed to genetic predisposition alone, and likely reflects in part, the contribution of overlapping mechanisms shared between these otherwise distinct disorders. There is accumulating evidence that dysregulated arginine metabolism and in particular, elevated arginase activity contributes to pulmonary complications in SCD. Derangements of arginine metabolism are also emerging as newly appreciated mechanism in both asthma and pulmonary hypertension independent of SCD. Patients with SCD may potentially be at risk for an asthma-like condition triggered or worsened by hemolysis-driven release of erythrocyte arginase and low nitric oxide bioavailability, in addition to classic familial asthma. Mechanisms that contributed to asthma are complex and multifactorial, influenced by genetic polymorphisms as well as environmental and infectious triggers. Given the association of asthma with inflammation, oxidative stress and hypoxemia, factors known to contribute to a vasculopathy in SCD, and the consequences of these factors on sickle erythrocytes, comorbid asthma would likely contribute to a vicious cycle of sickling and subsequent complications of SCD. Indeed a growing body of evidence documents what should come as no surprise: Asthma in SCD is associated with acute chest syndrome, stroke, pulmonary hypertension, and early mortality, and should therefore be aggressively managed based on established National Institutes of Health Guidelines for asthma management. Barriers to appropriate asthma management in SCD are discussed as well as strategies to overcome these obstacles in order to provide optimal care.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Adult
  • African Americans / statistics & numerical data
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / genetics
  • Anemia, Sickle Cell / physiopathology
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use*
  • Arginase / blood
  • Arginine / metabolism
  • Asthma / drug therapy*
  • Asthma / epidemiology
  • Asthma / etiology
  • Asthma / physiopathology
  • Asthma / therapy
  • Chest Pain / etiology
  • Chest Pain / physiopathology
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Comorbidity
  • Erythrocytes, Abnormal / enzymology
  • Erythrocytes, Abnormal / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Hypoxia / etiology
  • Hypoxia / physiopathology
  • Long QT Syndrome / etiology
  • Nitric Oxide / deficiency
  • Nitric Oxide / physiology
  • Oxidative Stress
  • Oxygen Inhalation Therapy
  • Prevalence
  • United States / epidemiology

Substances

  • Anti-Asthmatic Agents
  • Nitric Oxide
  • Arginine
  • Arginase