The use of chromones (cromoglycates) in the treatment of asthma
- James P Kemp, MD
James P Kemp, MD
- Clinical Professor of Pediatrics
- University of California School of Medicine
The drugs, cromolyn sodium (or cromolyn) and nedocromil, are commonly grouped together as chromones (also called cromoglycates). The chromones are listed as alternate initial controller therapies for mild asthma in national and international guidelines, although inhaled glucocorticoids (also known as inhaled corticosteroids) are the preferred agents [1,2]. The low incidence of side effects compared with inhaled glucocorticoids is a leading reason some patients prefer chromones over inhaled glucocorticoids.
This topic will review the pharmacology and use of chromones in the management of asthma. A more general discussion of asthma therapy is found separately. (See "An overview of asthma management".)
LIMITATIONS ON AVAILABILITY
Cromolyn first became available in the 1970s. At present, availability of cromoglycates varies from one country to another, due in part to the need to change the propellants used in cromoglycate metered-dose inhalers (MDIs) [3,4]. The propellant originally had been a chlorofluorocarbon (CFC). Following adoption of the Montreal protocol (an international agreement to ban CFCs), inhalers that contain hydrofluoroalkane (HFA) were developed for some drugs. HFA formulations of cromolyn are available in the United Kingdom and a Spinhaler device is available in Australia, although neither of these is sold in the United States. (See "The use of inhaler devices in adults" and "The use of inhaler devices in children".)
In the United States, neither cromolyn nor nedocromil is available in HFA-containing MDIs, and no formulation of nedocromil is marketed for asthma. As a result, the only remaining formulations for asthma are solutions of cromolyn (10 mg/mL) for nebulization. However, dry-powder inhaler formulations for cromolyn and nedocromil are available in other countries (table 1).
The chromones have potent effects in preventing both early and late asthmatic responses to inhaled allergens, such as pollen, and reducing airway reactivity to a range of inhaled irritants, such as sulfur dioxide and cold air .
- National Asthma Education and Prevention Program: Expert Panel Report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD. National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051) www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on March 17, 2016).
- Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA). www.ginasthma.org (Accessed on January 30, 2015).
- Netzer NC, Küpper T, Voss HW, Eliasson AH. The actual role of sodium cromoglycate in the treatment of asthma--a critical review. Sleep Breath 2012; 16:1027.
- Keller M, Schierholz J. Have inadequate delivery systems hampered the clinical success of inhaled disodium cromoglycate? Time for reconsideration. Expert Opin Drug Deliv 2011; 8:1.
- Holgate ST, Edwards AM. The chromones: Cromolyn sodium and nedocromil sodium. In: Middleton's allergy: Principles and practice, 6th ed, Adkinson NF, Yunginger JW, Busse WW, et al (Eds), Mosby, St. Louis 2003. p.915.
- Correia I, Wang L, Pang X, Theoharides TC. Characterization of the 78 kDa mast cell protein phosphorylated by the antiallergic drug cromolyn and homology to moesin. Biochem Pharmacol 1996; 52:413.
- Altounyan RE, Howell JB. Treatment of asthma with disodium cromoglycate (FPL 670, 'Intal'). Respiration 1969; 26:Suppl:131.
- Heinke S, Szücs G, Norris A, et al. Inhibition of volume-activated chloride currents in endothelial cells by chromones. Br J Pharmacol 1995; 115:1393.
- Mazurek N, Schindler H, Schürholz T, Pecht I. The cromolyn binding protein constitutes the Ca2+ channel of basophils opening upon immunological stimulus. Proc Natl Acad Sci U S A 1984; 81:6841.
- Loh RK, Jabara HH, Geha RS. Disodium cromoglycate inhibits S mu-->S epsilon deletional switch recombination and IgE synthesis in human B cells. J Exp Med 1994; 180:663.
- Hoag JE, McFadden ER Jr. Long-term effect of cromolyn sodium on nonspecific bronchial hyperresponsiveness: a review. Ann Allergy 1991; 66:53.
- Sadeghi-Hashjin G, Nijkamp FP, Henricks PA, Folkerts G. Sodium cromoglycate and doxantrazole are oxygen radical scavengers. Eur Respir J 2002; 20:867.
- Yang Y, Lu JY, Wu X, et al. G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium. Pharmacology 2010; 86:1.
- Latimer KM, O'Byrne PM, Morris MM, et al. Bronchoconstriction stimulated by airway cooling. Better protection with combined inhalation of terbutaline sulphate and cromolyn sodium than with either alone. Am Rev Respir Dis 1983; 128:440.
- Toogood JH, Lefcoe NM, Wonnacott TM, et al. Cromolyn sodium therapy: Predictors of response. Adv Asthma Allergy Pulm Dis 1978; 5:2.
- Donahue JG, Weiss ST, Livingston JM, et al. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997; 277:887.
- Bernstein IL, Siegel SC, Brandon ML, et al. A controlled study of cromolyn sodium sponsored by the Drug Committee of the American Academy of Allergy. J Allergy Clin Immunol 1972; 50:235.
- Sridhar AV, McKean M. Nedocromil sodium for chronic asthma in children. Cochrane Database Syst Rev 2006; :CD004108.
- Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med 2000; 343:1054.
- Guevara JP, Ducharme FM, Keren R, et al. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database Syst Rev 2006; :CD003558.
- Bukstein DA, Bratton DL, Firriolo KM, et al. Evaluation of parental preference for the treatment of asthmatic children aged 6 to 11 years with oral montelukast or inhaled cromolyn: a randomized, open-label, crossover study. J Asthma 2003; 40:475.
- Woolcock AJ. Treatment of asthma. In: Asthma and rhinitis, Busse WW, Holgate ST (Eds), Blackwell Scientific Publications, Boston and Oxford 1995. p.1364.
- Grigg CF. Responders and nonresponders to cromolyn sodium. Current Issues in Resp Med 1998; 2:2.
- König P, Grigg CF. Cromolyn sodium or nedocromil in childhood asthma: does it matter? Clin Exp Allergy 2000; 30:164.
- Marin JM, Carrizo SJ, Garcia R, Ejea MV. Effects of nedocromil sodium in steroid-resistant asthma: a randomized controlled trial. J Allergy Clin Immunol 1996; 97:602.
- Svendsen UG, Jørgensen H. Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma. Eur Respir J 1991; 4:992.
- Holgate ST. The efficacy and therapeutic position of nedocromil sodium. Respir Med 1996; 90:391.
- LIMITATIONS ON AVAILABILITY
- ROLE IN ASTHMA THERAPY
- Prevention of acute bronchoconstriction
- Efficacy as long-term maintenance therapy
- - Compared with inhaled glucocorticoids
- - Compared with other controller agents
- CLINICAL USE
- Choice of drug
- Initial dosing
- - Cromolyn
- - Nedocromil
- Adverse effects
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS