Asthma management: Reinventing the wheel in sickle cell disease

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. Am. J. Hematol. 84:234-241, 2009. V

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Asthma or recurrent wheezing, a major correlate of asthma, has recently been recognized as an important comorbidity in children and adults with SCD, with a reported prevalence of 7 to 30% [93][94][95]. In individuals with SCD, asthma is associated with increased frequency of pain episodes and ACS [96], as well as significantly higher mortality [94,97].…”

“…In individuals with SCD, asthma is associated with increased frequency of pain episodes and ACS [96], as well as significantly higher mortality [94,97]. This was most clearly demonstrated in data from the CSSCD cohort where 1,963 individuals with SCA who were classifiable for asthma were followed for a total of 18,495 patientyears.…”

Pulmonary Complications of Sickle Cell Disease

“…Asthma affects approximately 12% of all United States children (58), 15 to 20% of African American children, and 9% of African American adults (20,58,59). The prevalence of asthma among pediatric patients with SCD appears to be similar to that in children of African descent in the general population (57,60).…”

“…Patients with asthma with SCD should be treated similarly to patients without SCD in accordance with National Institutes of Health (NIH) guidelines (58,64). The primary concerns associated with short-term systemic corticosteroid use in patients with SCD presenting with severe asthma are rebound VOC events and theoretical concerns of arrhythmia associated with QT prolongation.…”

“…Emergency department care should include oxygen, a short-acting b 2 -agonist, and systemic corticosteroids for moderate or severe exacerbations. Magnesium sulfate may be considered for severe cases (58). A low threshold for hospital admission should exist.…”