Conflict of Interest: Nothing to report.
Critical Review
You have full text access to this OnlineOpen article
Asthma management: Reinventing the wheel in sickle cell disease†
Article first published online: 31 DEC 2008
DOI: 10.1002/ajh.21359
Copyright © 2008 Wiley-Liss, Inc.
Additional Information
How to Cite
Morris, C. R. (2009), Asthma management: Reinventing the wheel in sickle cell disease. Am. J. Hematol., 84: 234–241. doi: 10.1002/ajh.21359
- †
Publication History
- Issue published online: 25 MAR 2009
- Article first published online: 31 DEC 2008
- Accepted manuscript online: 31 DEC 2008 12:00AM EST
- Manuscript Accepted: 22 DEC 2008
- Manuscript Revised: 21 DEC 2008
- Manuscript Received: 29 OCT 2008
References
- 1. Asthma in children. N Engl J Med 1992; 326: 1540–1545.
- 2,,, et al. Airway remodeling in asthma. J Clin Invest 1999; 104: 1001–1006.
- 3,,, et al. New insights into the pathogenesis of asthma. J Clin Invest 2003; 111: 291–297.
- 4
- 5,,, et al. Prevalence and reversibility of lower airway obstruction in children with sickle cell disease. J Pediatr 2001; 138: 188–192.
- 6,,, et al. Elevated arginase activity and limited arginine bioavailability: A common feature of asthma and sickle cell disease. Blood 2003; 102: 764a (abstr 2819).
- 7,,, et al. Asthma and acute chest in sickle-cell disease. Pediatr Pulmonol 2004; 38: 229–232.Direct Link:
- 8
- 9,,, et al. Asthma in children with sickle cell disease and its association with acute chest syndrome. Thorax 2005; 60: 206–210.
- 10
- 11,,, et al. Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood 2006; 108: 2923–2927.
- 12,,, et al. Temporal relationship of asthma to acute chest syndrome in sickle cell disease. Pediatr Pulmonol 2007; 42: 103–106.Direct Link:
- 13,,, et al. Asthma is associated with increased mortality in patients with sickle cell anemia. Haematologica 2007; 92: 1115–1118.
- 14,,, et al. Clinical differences between children and adults with pulmonary hypertension and sickle cell disease. Br J Haematol 2008; 140: 104–112.
- 15
- 16,,, et al. Physician-diagnosed asthma and acute chest syndrome: Associations with NOS Polymorphisms. Pediatr Pulmonol 2007; 42: 332–338.Direct Link:
- 17,,, et al. Abnormal pulmonary function in adults and children with sickle cell disease. Blood 2005; 106: 652a (abstr 2319).
- 18,,, et al. Asthma is associated with acute chest syndrome, but not with an increased rate of hospitalization for pain among children in France with sickle cell anemia: A retrospective cohort study. Haematologica 2008; 93: 1917–1918.
- 19,,, et al. Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood 2008; 112: 2529–2538.
- 20New NHLBI guidelines for the diagnosis and management of asthma. National Heart, Lung and Blood Institute. Lippincott Health Promot Lett 1997; 2: 1,8–9.
- 21,,, et al. Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network. J Allergy Clin Immunol 2007; 119: 3–11; quiz 12-13.
- 22,,, et al. National Heart, Lung, and Blood Institute guidelines and asthma management practices among inner-city pediatric primary care providers. Chest 2006; 129: 619–623.
- 23. Update in asthma 2007. Am J Respir Crit Care Med 2008; 177: 1068–1073.
- 24National Asthma Education and Prevention Program Expert Panel Report 3. Guidelines for the diagnosis and management of asthma. Bethesda: National Heart, Lung and Blood Institutes, National Institutes of Health; 2007.
- 25,,, et al. Asthma in California: Findings from the 2001 California Health Interview Survey. Los Angeles: UCLA Center for Health Policy Research; 2003.
- 26,. Prevalence and consequences of asthma and wheezing in African-American and White adolescents. J Adolesc Health 2001; 29: 314–319.
- 27,,, et al. Prevalence of asthma and asthma-like symptoms in inner-city elementary schoolchildren. Pediatr Pulmonol 2002; 34: 105–111.Direct Link:
- 28,,, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004; 350: 22–31.
- 29,,, et al. Pulmonary hypertension in sickle cell disease. Am J Med 2004; 117: 665–669.
- 30. Pulmonary hypertension of sickle cell disease: More than just another lung disease. Am J Hematol 2008; 83: 4–5.Direct Link:
- 31,,, et al. Pulmonary hypertension associated with sickle cell disease: Clinical and laboratory endpoints and disease outcomes. Am J Hematol 2008; 83: 19–25.Direct Link:
- 32,,, et al. Pulmonary hypertension in sickle cell disease: A common complication for both adults and children. The 27th Annual Meeting of the National Sickle Cell Program. Los Angeles, CA; 2003.
- 33,,. Pulmonary hypertension in sickle cell disease: Relevance to children. Pediatr Hematol Oncol 2007; 24: 159–170.
- 34,,, et al. Prevalence and risk factors of elevated pulmonary artery pressures in children with sickle cell disease. Pediatrics 2008; 121: 777–782.
- 35,,, et al. Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol 2008; 29: 309–312.
- 36,. Pulmonary complications of sickle cell disease in children. Curr Opin Pediatr 2008; 20: 279–287.
- 37,,, et al. Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease. Am J Hematol 2008; 83: 6–14.Direct Link:
- 38
- 39,,. Incidence and significance of sickle cell trait in asthma. Ann Allergy 1972; 30: 623–626.
- 40,,, et al. Patterns of arginine and nitric oxide in sickle cell disease patients with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 2000; 22: 515–520.
- 41,,, et al. Arginine therapy: A novel strategy to increase nitric oxide production in sickle cell disease. Brit J Haematol 2000; 111: 498–500.
- 42,,, et al. Arginine therapy: A new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med 2003; 168: 63–69.
- 43,,, et al. Decreased arginine bioavailability and increased arginase activity in asthma. Am J Respir Crit Care Med 2004; 170: 148–153.
- 44
- 45
- 46
- 47,,, et al. Evidence for a metabolic shift of arginine metabolism in sickle cell disease. Ann Hematol 2004; 83: 371–375.
- 48,,. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med 2006; 41: 1771–1780.
- 49,,, et al. Plasma concentrations of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell patients but do not increase further during painful crisis. Am J Hematol 2008; 83: 577–579.Direct Link:
- 50,,, et al. Arginine therapy of transgenic-knockout sickle mice improves microvascular function by reducing non-nitric oxide vasodilators, hemolysis and oxidative stress. Am J Physiol Heart Circ Physiol 2008; 295: H39–H47.
- 51,,, et al. Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease. Ann Hematol 2005; 84: 282–286.
- 52,,, et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 2007; 109: 3088–3098.
- 53,,, et al. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med 2006; 40: 1443–1453.
- 54,,. Nitric oxide and arginine dysregulation: A novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med 2008; 8: 620–632.
- 55,,, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension and mortality in sickle cell disease. JAMA 2005; 294: 81–90.
- 56,,, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003; 111: 1863–1874.
- 57,,. Arginase and asthma: Novel insights into nitric oxide homeostatis and airway hyperresponsiveness. Trends Pharmacol Sci 2003; 24: 450–455.
- 58,,. Arginine in asthma and lung inflammation. J Nutr 2004; 134: 2830S–2836S; discussion 2853S.
- 59,,, et al. Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma. Respir Res 2006; 7: 6.
- 60,,, et al. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. J Allergy Clin Immunol 2006; 117: 119–126.
- 61,,, et al. Alterations of the arginine metabolome in asthma. Am J Respir Crit Care Med 2008; 178: 673–681.
- 62,,, et al. ARG1 is a novel bronchodilator response gene: Screening and replication in four asthma cohorts. Am J Respir Crit Care Med 2008; 178: 688–694.
- 63,,, et al. Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation. Am J Respir Crit Care Med 2008; 178: 565–573.
- 64,,. Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. Biol Neonate 1994; 66: 65–70.
- 65,,, et al. Decreased arginine bioavailability contributes to the pathogenesis of pulmonary artery hypertension. American College of Cardiology Annual Meeting, Orlando, Florida; 2005.
- 66,,, et al. Hemolysis-associated pulmonary hypertension in thalassemia. Ann N Y Acad Sci 2005; 1054: 481–485.Direct Link:
- 67,,. Pulmonary hypertension in thalassemia: Association with hemolysis, arginine metabolism dysregulation and a hypercoaguable state. Adv Pulm Hypertens 2007; 5: 31–38.
- 68
- 69,. Arginine metabolism: Nitric oxide and beyond. Biochem J 1998; 336: 1–17.
- 70,,, et al. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease. JAMA 2005; 293: 1653–1662.
- 71,. Association of L-arginine transporters with fodrin: Implications for hypoxic inhibition of arginine uptake. Am J Physiol Lung Cell Mol Physiol 2000; 278: L111–L117.
- 72,,. The transport activity of the human cationic amino acid transporter hCAT-1 is downregulated by activation of protein kinase C. Br J Pharmacol 2001; 132: 1193–1200.Direct Link:
- 73,,, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle cell disease. Nat Med 2002; 8: 1383–1389.
- 74
- 75,,, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 2001; 98: 15215–15220.
- 76,. Oxidant-mediated impairment of nitric oxide signaling in sickle cell disease–mechanisms and consequences. Cell Mol Biol (Noisy-le-grand) 2004; 50: 95–105.
- 77,. Superoxide dismutase, glutathione peroxidase, catalase and lipid peroxidation of normal and sickled erythrocytes. Br J Haematol 1980; 44: 87–92.Direct Link:
- 78,,, et al. Altered amount and activity of superoxide dismutase in sickle cell disease. FASEB J 1988; 2: 237–243.
- 79,,, et al. Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc Natl Acad Sci USA 1996; 93: 6770–6774.
- 80,,. Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 2007; 21: 37–47.
- 81,,, et al. Evidence for a metabolic shift of arginine metabolism in sickle cell disease. Ann Hematol 2004; 83: 371–375.
- 82,,. Arginase and asthma: Novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003; 24: 450–455.
- 83,,, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003; 111: 1863–1874.
- 84,,. The therapeutic potential of drugs targeting the arginase pathway in asthma. Expert Opin Invest Drugs 2005; 14: 1221–1231.
- 85,,, et al. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 2004; 170: 148–153.
- 86,,, et al. Role of L-arginine in the deficiency of nitric oxide and airway hyperreactivity after the allergen-induced early asthmatic reaction in guinea-pigs. Br J Pharmacol 1999; 128: 1114–1120.Direct Link:
- 87,,, et al. Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. Transplantation 1995; 59: 1542–1549.
- 88,,, et al. Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome. Am J Respir Crit Care Med 2001; 164: 2186–2190.
- 89,,, et al. Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol 2008; 29: 309–12.
- 90,,, et al. Major gene effect and additive familial pattern of inheritance of asthma exist among families of probands with sickle cell anemia and asthma. Am J Hum Biol 2008; 20: 149–153.Direct Link:
- 91,,, et al. Comparison of airway reactivity induced by cold air and metacholine challenges in asthmatic children. Pediatr Pulmonol 1995; 19: 326–329.Direct Link:
- 92,,, et al. Lung function and airway hyperresponsiveness in adult patients with sickle cell disease. Am J Med Sci 2006; 332: 68–72.
- 93,,, et al. Airway hyperreactivity detected by methacholine challenge in children with sickle cell disease. Pediatr Pulmonol 2007; 42: 1187–1192.Direct Link:
- 94,,, et al. Methacholine challenge in children with sickle cell disease: A case series. Pediatr Pulmonol 2008; 43: 924–929.Direct Link:
- 95,,. Longitudinal changes in lung function and somatic growth in children with sickle cell disease. Pediatr Pulmonol 2007; 42: 483–488.Direct Link:
- 96,,, et al. Longitudinal decline in lung volume in a population of children with sickle cell disease. Am J Respir Crit Care Med 2008; 178: 1005–1009.
- 97,,, et al. Longitudinal analysis of pulmonary function in adults with sickle cell disease. Am J Hematol 2008; 32: 85–96.
- 98,,, et al. Abnormal pulmonary function in adults with sickle cell anemia. Am J Respir Crit Care Med 2006; 173: 1264–1269.
- 99,. Pulmonary complications of sickle cell disease. N Engl J Med 2008; 359: 2254–2265.
- 100,,, et al. Correlation between spirometry and impulse oscillometry in children with asthma. Acta Paediatr 2008; 97: 51–54.Direct Link:
- 101,,, et al. Sibling history of asthma is a risk factor for pain in children with sickle cell anemia. Am J Hematol 2008; 83: 855–857.Direct Link:
- 102,,, et al. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood 2007; 110: 2708–2717.
- 103,,, et al. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood 2004; 104: 3774–3781.
- 104,,, et al. Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium. Blood 2008; 112: 3474–3483.
- 105
- 106,,, et al. Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. Blood 2003; 101: 3281–3287.
- 107,,, et al. β(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol 2008; 141: 105–108.Direct Link:
- 108,,, et al. Prolonged QT interval in pediatric sickle cell disease. Pediatr Blood Cancer 2006; 47: 831–833.Direct Link:
- 109,,, et al. Assessment of corrected QT interval in sickle-cell disease patients who undergo erythroapheresis. Transfus Med 2007; 17: 466–472.
- 110,,, et al. Increased QT dispersion in sickle cell disease: Effect of pulmonary hypertension. Acta Haematol 2007; 118: 1–6.
- 111,,, et al. Risk of cardiac events in patients with asthma and long-QT syndrome treated with β(2) agonists. Am J Cardiol 2008; 102: 871–874.
- 112,. Sudden death in sickle cell disease. J R Soc Med 1993; 86: 484–485.
- 113,,, et al. Cardiovascular autonomic dysfunction in sickle cell anemia: A possible risk factor for sudden death? Clin Auton Res 1997; 7: 121–125.
- 114,,, et al. Causes of death in sickle cell disease: An autopsy study. Br J Haematol 2003; 123: 359–365.Direct Link:
- 115,,, et al. Circumstances of death in adult sickle cell disease patients. Am J Hematol 2006; 81: 858–863.Direct Link:
- 116,,, et al. Sickle cell lung disease and sudden death: A retrospective/prospective study of 21 autopsy cases and literature review. Am J Forensic Med Pathol 2007; 28: 168–172.
- 117,. Sickle cell crisis following intraarticular steroid therapy for rheumatoid arthritis. Arthritis Rheum 1987; 30: 1065–1068.Direct Link:
- 118,,, et al. Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease. Pediatr Blood Cancer 2008; 50: 1006–1012.Direct Link:
- 119,,, et al. Severe vaso-occlusive episodes associated with use of systemic corticosteroids in patients with sickle cell disease. J Natl Med Assoc 2008; 100: 948–951.
- 120,,. High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease. N Engl J Med 1994; 330: 733–737.
- 121. Reversal of sickle-cell crisis by dexamethasone. Lancet 1979; 1: 1088.
- 122,,, et al. Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease. Blood 1998; 92: 3082–3089.
- 123,,. A single-institution experience with treatment of severe acute chest syndrome: Lack of rebound pain with dexamethasone plus transfusion therapy. J Pediatr Hematol Oncol 2008; 30: 322–325.
- 124,,, et al. Effects of oxygen inhalation on endogenous erythropoietin kinetics, erythropoiesis, and properties of blood cells in sickle-cell anemia. N Engl J Med 1984; 311: 291–295.
- 125,,, et al. Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease. Br J Haematol 2007; 136: 319–325.Direct Link:
- 126,,. Clinician assessment for acute chest syndrome in febrile patients with sickle cell disease: Is it accurate enough? Ann Emerg Med 1999; 34: 64–69.
- 127,,, et al. Plasma and urinary leukotrienes in sickle cell disease: Possible role in the inflammatory process [see comments]. Eur J Clin Invest 1994; 24: 57–64.Direct Link:
- 128,,, et al. Elevated urinary leukotriene E4 levels are associated with hospitalization for pain in children with sickle cell disease. Am J Hematol 2008; 83: 640–643.Direct Link:
- 129,,. Fat embolism syndrome associated with asthma and sickle cell-β+ -thalassemia. Am JHematol 1994; 46: 354–357.Direct Link:
- 130,,, et al. Painful episodes in children with sickle cell disease and asthma are temporally associated with respiratory symptoms. J Pediatr Hematol Oncol 2006; 28: 481–485.
- 131,,, et al. Reversible loss of pulmonary function induced by acute chest syndrome in sickle cell disease. Blood 2005; 106: 96a [abstr 315].
- 132,,, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National acute chest syndrome study group. N Engl J Med 2000; 342: 1855–1865.
- 133,. Current thinking on the relationship between rhinosinusitis and asthma. J Asthma 2005; 42: 1–7.
- 134,,, et al. Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthma. Chest, 2008. Oct 10 [Epub ahead of print].
- 135,,. Prevalence and impact of gastroesophageal reflux in adolescents with asthma: A population-based study. Pediatr Pulmonol 2006; 41: 475–481.Direct Link:

1096-8652/asset/olbannerleft.gif?v=1&s=d9288d4b31f0b8e9a1eb2d195cb165e0aa1d7a97)
1096-8652/asset/olbannerright.gif?v=1&s=78488ac502104a3d829e729353def6ce62dc1e29)
1096-8652/asset/cover.gif?v=1&s=d31a603f9c7a1894ee3b68044c6fdcbe64ff8068)