Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1994;3(7):S15–S19. doi: 10.1155/S0962935194000694

Cromoglycate and Nedocromil: Influence on Airway Reactivity

E A Valletta 1,2, A L Boner 1,2,✉
PMCID: PMC2365598  PMID: 18475597

Abstract

Although basic mechanisms of bronchial hyper-responsiveness (BHR) are still incompletely understood, inflammation of airways is likely to play a fundamental role in modulating BHR in patients with asthma. The involvement of several inflammatory cells (eosinophils, mast cells, lymphocytes, neutrophils, macrophages and platelets) and of bioactive mediators secreted by these cells in the pathogenesis of asthma is well documented. Sodium cromoglycate and nedocromil sodium are two pharmacological agents which have anti-allergic and anti-inflammatory properties. Their clinical effectiveness in mild to moderate asthma, and the capacity to reduce BHR under different natural and experimental conditions, make them valuable drugs for maintenance therapy in patients with asthma.

Full Text

The Full Text of this article is available as a PDF (562.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham W. M., Stevenson J. S., Chapman G. A., Tallent M. W., Jackowski J. The effect of nedocromil sodium and cromolyn sodium on antigen-induced responses in allergic sheep in vivo and in vitro. Chest. 1987 Nov;92(5):913–917. doi: 10.1378/chest.92.5.913. [DOI] [PubMed] [Google Scholar]
  2. Anderson S. D. Bronchial challenge by ultrasonically nebulized aerosols. Clin Rev Allergy. 1985 Oct;3(4):427–439. [PubMed] [Google Scholar]
  3. Barnes P. J. Effect of nedocromil sodium on airway sensory nerves. J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):182–186. doi: 10.1016/0091-6749(93)90103-m. [DOI] [PubMed] [Google Scholar]
  4. Beasley R., Roche W. R., Roberts J. A., Holgate S. T. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989 Mar;139(3):806–817. doi: 10.1164/ajrccm/139.3.806. [DOI] [PubMed] [Google Scholar]
  5. Bel E. H., Timmers M. C., Hermans J., Dijkman J. H., Sterk P. J. The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects. Am Rev Respir Dis. 1990 Jan;141(1):21–28. doi: 10.1164/ajrccm/141.1.21. [DOI] [PubMed] [Google Scholar]
  6. Boner A. L., Niero E., Antolini I., Valletta E. A., Gaburro D. Pulmonary function and bronchial hyperreactivity in asthmatic children with house dust mite allergy during prolonged stay in the Italian Alps (Misurina, 1756 m). Ann Allergy. 1985 Jan;54(1):42–45. [PubMed] [Google Scholar]
  7. Boner A. L., Niero E., Grigolini C., Valletta E. A., Biancotto R., Gaburro D. Inhibition of exercise-induced asthma by three forms of sodium cromoglycate. Eur J Respir Dis. 1985 Jan;66(1):21–24. [PubMed] [Google Scholar]
  8. Boner A. L., Vallone G., Bennati D. Nedocromil sodium in exercise-induced bronchoconstriction in children. Ann Allergy. 1989 Jan;62(1):38–41. [PubMed] [Google Scholar]
  9. Boushey H. A., Holtzman M. J., Sheller J. R., Nadel J. A. Bronchial hyperreactivity. Am Rev Respir Dis. 1980 Feb;121(2):389–413. doi: 10.1164/arrd.1980.121.2.389. [DOI] [PubMed] [Google Scholar]
  10. Bruijnzeel P. L., Warringa R. A., Kok P. T., Hamelink M. L., Kreukniet H., Koenderman L. Effects of nedocromil sodium on in vitro induced migration, activation, and mediator release from human granulocytes. J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):159–164. doi: 10.1016/0091-6749(93)90099-2. [DOI] [PubMed] [Google Scholar]
  11. Church M. K., Young K. D. The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol. 1983 Apr;78(4):671–679. doi: 10.1111/j.1476-5381.1983.tb09419.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cockcroft D. W., Killian D. N., Mellon J. J., Hargreave F. E. Protective effect of drugs on histamine-induced asthma. Thorax. 1977 Aug;32(4):429–437. doi: 10.1136/thx.32.4.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cockcroft D. W., Murdock K. Y. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol. 1987 May;79(5):734–740. doi: 10.1016/0091-6749(87)90204-1. [DOI] [PubMed] [Google Scholar]
  14. Comis A., Valletta E. A., Sette L., Andreoli A., Boner A. L. Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children. Eur Respir J. 1993 Apr;6(4):523–526. [PubMed] [Google Scholar]
  15. Crimi N., Palermo F., Oliveri R., Cacopardo B., Vancheri C., Mistretta A. Adenosine-induced bronchoconstriction: comparison between nedocromil sodium and sodium cromoglycate. Eur J Respir Dis Suppl. 1986;147:258–262. [PubMed] [Google Scholar]
  16. Davies S. E. Effect of disodium cromoglycate on exercise-induced asthma. Br Med J. 1968 Sep 7;3(5618):593–594. doi: 10.1136/bmj.3.5618.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Di Maria G. U., Bellofiore S., Ciancio N., Ruggieri F., Mistretta A. Nedocromil sodium inhibits the increase in airway reactivity induced by platelet activating factor in humans. Chest. 1992 Jul;102(1):123–128. doi: 10.1378/chest.102.1.123. [DOI] [PubMed] [Google Scholar]
  18. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  19. Dolovich J., Hargreave F. The asthma syndrome: inciters, inducers, and host characteristics. Thorax. 1981 Sep;36(9):614–644. doi: 10.1136/thx.36.9.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dorward A. J., Roberts J. A., Thomson N. C. Effect of nedocromil sodium on histamine airway responsiveness in grass-pollen sensitive asthmatics during the pollen season. Clin Allergy. 1986 Jul;16(4):309–315. doi: 10.1111/j.1365-2222.1986.tb01962.x. [DOI] [PubMed] [Google Scholar]
  21. Eggleston P. A. Upper airway inflammatory diseases and bronchial hyperresponsiveness. J Allergy Clin Immunol. 1988 May;81(5 Pt 2):1036–1041. doi: 10.1016/0091-6749(88)90176-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Flint K. C., Leung K. B., Hudspith B. N., Brostoff J., Pearce F. L., Johnson N. M. Bronchoalveolar mast cells in extrinsic asthma: a mechanism for the initiation of antigen specific bronchoconstriction. Br Med J (Clin Res Ed) 1985 Oct 5;291(6500):923–926. doi: 10.1136/bmj.291.6500.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Flint K. C., Leung K. B., Pearce F. L., Hudspith B. N., Brostoff J., Johnson N. M. Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of sodium cromoglycate. Clin Sci (Lond) 1985 Apr;68(4):427–432. doi: 10.1042/cs0680427. [DOI] [PubMed] [Google Scholar]
  24. Foo A. L., Lanteri C. J., Burton P. R., Sly P. D. The effect of nedocromil sodium on histamine responsiveness in clinically stable asthmatic children. J Asthma. 1993;30(5):381–390. doi: 10.3109/02770909309056742. [DOI] [PubMed] [Google Scholar]
  25. Furukawa C. T., Shapiro G. G., Bierman C. W., Kraemer M. J., Ward D. J., Pierson W. E. A double-blind study comparing the effectiveness of cromolyn sodium and sustained-release theophylline in childhood asthma. Pediatrics. 1984 Oct;74(4):453–459. [PubMed] [Google Scholar]
  26. Gonzalez J. P., Brogden R. N. Nedocromil sodium. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of reversible obstructive airways disease. Drugs. 1987 Nov;34(5):560–577. doi: 10.2165/00003495-198734050-00004. [DOI] [PubMed] [Google Scholar]
  27. Griffin M. P., MacDonald N., McFadden E. R., Jr Short- and long-term effects of cromolyn sodium on the airway reactivity of asthmatics. J Allergy Clin Immunol. 1983 Mar;71(3):331–338. doi: 10.1016/0091-6749(83)90088-x. [DOI] [PubMed] [Google Scholar]
  28. Groot C. A., Lammers J. W., Molema J., Festen J., van Herwaarden C. L. Effect of inhaled beclomethasone and nedocromil sodium on bronchial hyperresponsiveness to histamine and distilled water. Eur Respir J. 1992 Oct;5(9):1075–1082. [PubMed] [Google Scholar]
  29. Hargreave F. E., Dolovich J., O'Byrne P. M., Ramsdale E. H., Daniel E. E. The origin of airway hyperresponsiveness. J Allergy Clin Immunol. 1986 Nov;78(5 Pt 1):825–832. doi: 10.1016/0091-6749(86)90226-5. [DOI] [PubMed] [Google Scholar]
  30. Harries M. G. Bronchial irritant receptors and a possible new action for cromolyn sodium. Ann Allergy. 1981 Mar;46(3):156–158. [PubMed] [Google Scholar]
  31. Hughes J. M., McKay K. O., Johnson P. R., Tragoulias S., Black J. L., Armour C. L. Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation. Clin Exp Allergy. 1993 Apr;23(4):251–256. doi: 10.1111/j.1365-2222.1993.tb00318.x. [DOI] [PubMed] [Google Scholar]
  32. Ioli F., Donner C. F., Fracchia C., Patessio A., Aprile C. Sustained-release anhydrous theophylline in preventing exercise-induced asthma. Respiration. 1984;46(1):105–113. doi: 10.1159/000194677. [DOI] [PubMed] [Google Scholar]
  33. Joseph M., Tsicopoulos A., Tonnel A. B., Capron A. Modulation by nedocromil sodium of immunologic and nonimmunologic activation of monocytes, macrophages, and platelets. J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):165–170. doi: 10.1016/0091-6749(93)90100-t. [DOI] [PubMed] [Google Scholar]
  34. Kaliner M. A. How the current understanding of the pathophysiology of asthma influences our approach to therapy. J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):144–147. doi: 10.1016/0091-6749(93)90096-x. [DOI] [PubMed] [Google Scholar]
  35. Koenig J. Q., Marshall S. G., van Belle G., McManus M. S., Bierman C. W., Shapiro G. G., Furukawa C. T., Pierson W. E. Therapeutic range cromolyn dose-response inhibition and complete obliteration of SO2-induced bronchoconstriction in atopic adolescents. J Allergy Clin Immunol. 1988 May;81(5 Pt 1):897–901. doi: 10.1016/0091-6749(88)90947-5. [DOI] [PubMed] [Google Scholar]
  36. Laitinen L. A., Venho K., Poppius H. A controlled study on the effect of treatment with cromolyn sodium pressurized aerosol on bronchial reactivity in patients with asthma. Ann Allergy. 1986 Mar;56(3):270–273. [PubMed] [Google Scholar]
  37. Lemire I., Cartier A., Malo J. L., Pineau L., Ghezzo H., Martin R. R. Effect of sodium cromoglycate on histamine inhalation tests. J Allergy Clin Immunol. 1984 Feb;73(2):234–239. doi: 10.1016/s0091-6749(84)80013-5. [DOI] [PubMed] [Google Scholar]
  38. Leung K. B., Flint K. C., Brostoff J., Hudspith B. N., Johnson N. M., Lau H. Y., Liu W. L., Pearce F. L. Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells. Thorax. 1988 Oct;43(10):756–761. doi: 10.1136/thx.43.10.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lozewicz S., Gomez E., Ferguson H., Davies R. J. Inflammatory cells in the airways in mild asthma. BMJ. 1988 Dec 10;297(6662):1515–1516. doi: 10.1136/bmj.297.6662.1515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Löwhagen O., Rak S. Bronchial hyperreactivity after treatment with sodium cromoglycate in atopic asthmatic patients not exposed to relevant allergens. J Allergy Clin Immunol. 1985 Mar;75(3):343–347. doi: 10.1016/0091-6749(85)90070-3. [DOI] [PubMed] [Google Scholar]
  41. Löwhagen O., Rak S. Modification of bronchial hyperreactivity after treatment with sodium cromoglycate during pollen season. J Allergy Clin Immunol. 1985 Apr;75(4):460–467. doi: 10.1016/s0091-6749(85)80018-x. [DOI] [PubMed] [Google Scholar]
  42. Martin A. J., Landau L. I., Phelan P. D. Lung function in young adults who had asthma in childhood. Am Rev Respir Dis. 1980 Oct;122(4):609–616. doi: 10.1164/arrd.1980.122.4.609. [DOI] [PubMed] [Google Scholar]
  43. Martinez F. D., Morgan W. J., Wright A. L., Holberg C. J., Taussig L. M. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med. 1988 Oct 27;319(17):1112–1117. doi: 10.1056/NEJM198810273191702. [DOI] [PubMed] [Google Scholar]
  44. Mattoli S., Foresi A., Corbo G. M., Polidori G., Ciappi G. Protective effect of disodium cromoglycate on allergen-induced bronchoconstriction and increased hyperresponsiveness: a double-blind placebo-controlled study. Ann Allergy. 1986 Oct;57(4):295–300. [PubMed] [Google Scholar]
  45. Mattoli S., Foresi A., Corbo G. M., Valente S., Ciappi G. Effects of two doses of cromolyn on allergen-induced late asthmatic response and increased responsiveness. J Allergy Clin Immunol. 1987 May;79(5):747–754. doi: 10.1016/0091-6749(87)90206-5. [DOI] [PubMed] [Google Scholar]
  46. Mazurek N., Berger G., Pecht I. A binding site on mast cells and basophils for the anti-allergic drug cromolyn. Nature. 1980 Aug 14;286(5774):722–723. doi: 10.1038/286722a0. [DOI] [PubMed] [Google Scholar]
  47. Nair N., Hopp R. J., Townley R. Effect of nedocromil on antigen-induced bronchoconstriction in asthmatic subjects. Ann Allergy. 1989 Apr;62(4):329–331. [PubMed] [Google Scholar]
  48. O'Byrne P. M., Dolovich J., Hargreave F. E. Late asthmatic responses. Am Rev Respir Dis. 1987 Sep;136(3):740–751. doi: 10.1164/ajrccm/136.3.740. [DOI] [PubMed] [Google Scholar]
  49. Pattemore P. K., Holgate S. T. Bronchial hyperresponsiveness and its relationship to asthma in childhood. Clin Exp Allergy. 1993 Nov;23(11):886–900. doi: 10.1111/j.1365-2222.1993.tb00273.x. [DOI] [PubMed] [Google Scholar]
  50. Pearce F. L. Effect of nedocromil sodium on mediator release from mast cells. J Allergy Clin Immunol. 1993 Jul;92(1 Pt 2):155–158. doi: 10.1016/0091-6749(93)90098-z. [DOI] [PubMed] [Google Scholar]
  51. Pearce F. L., Flint K. C., Leung K. B., Hudspith B. N., Seager K., Hammond M. D., Brostoff J., Geraint-James D., Johnson N. M. Some studies on human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymic dissociation of whole lung tissue. Int Arch Allergy Appl Immunol. 1987;82(3-4):507–512. doi: 10.1159/000234266. [DOI] [PubMed] [Google Scholar]
  52. Peat J. K., Britton W. J., Salome C. M., Woolcock A. J. Bronchial hyperresponsiveness in two populations of Australian schoolchildren. II. Relative importance of associated factors. Clin Allergy. 1987 Jul;17(4):283–290. doi: 10.1111/j.1365-2222.1987.tb02016.x. [DOI] [PubMed] [Google Scholar]
  53. Peroni D. G., Melotti P., Piacentini G. L., Bonizzato C., Boner A. L. Effects of nedocromil sodium on the binding of N-formyl-methionyl-leucyl-phenylalanine in human neutrophils. Agents Actions. 1992 Jul;36(3-4):212–214. [PubMed] [Google Scholar]
  54. Petty T. L., Rollins D. R., Christopher K., Good J. T., Oakley R. Cromolyn sodium is effective in adult chronic asthmatics. Am Rev Respir Dis. 1989 Mar;139(3):694–701. doi: 10.1164/ajrccm/139.3.694. [DOI] [PubMed] [Google Scholar]
  55. Platts-Mills T. A., Tovey E. R., Mitchell E. B., Moszoro H., Nock P., Wilkins S. R. Reduction of bronchial hyperreactivity during prolonged allergen avoidance. Lancet. 1982 Sep 25;2(8300):675–678. doi: 10.1016/s0140-6736(82)90709-7. [DOI] [PubMed] [Google Scholar]
  56. Rebuck A. S., Kesten S., Boulet L. P., Cartier A., Cockcroft D., Gruber J., Laberge F., Lee-Chuy E., Keshmiri M., MacDonald G. F. A 3-month evaluation of the efficacy of nedocromil sodium in asthma: a randomized, double-blind, placebo-controlled trial of nedocromil sodium conducted by a Canadian multicenter study group. J Allergy Clin Immunol. 1990 Mar;85(3):612–617. doi: 10.1016/0091-6749(90)90101-9. [DOI] [PubMed] [Google Scholar]
  57. Robertson D. G., Kerigan A. T., Hargreave F. E., Chalmers R., Dolovich J. Late asthmatic responses induced by ragweed pollen allergen. J Allergy Clin Immunol. 1974 Oct;54(4):244–254. doi: 10.1016/0091-6749(74)90067-0. [DOI] [PubMed] [Google Scholar]
  58. Robuschi M., Vaghi A., Simone P., Bianco S. Prevention of fog-induced bronchospasm by nedocromil sodium. Clin Allergy. 1987 Jan;17(1):69–74. doi: 10.1111/j.1365-2222.1987.tb02321.x. [DOI] [PubMed] [Google Scholar]
  59. Svendsen U. G., Frølund L., Madsen F., Nielsen N. H., Holstein-Rathlou N. H., Weeke B. A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma. J Allergy Clin Immunol. 1987 Jul;80(1):68–74. doi: 10.1016/s0091-6749(87)80193-8. [DOI] [PubMed] [Google Scholar]
  60. Warner J. O. Significance of late reactions after bronchial challenge with house dust mite. Arch Dis Child. 1976 Dec;51(12):905–911. doi: 10.1136/adc.51.12.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wells E., Mann J. Phosphorylation of a mast cell protein in response to treatment with anti-allergic compounds. Implications for the mode of action of sodium cromoglycate. Biochem Pharmacol. 1983 Mar 1;32(5):837–842. doi: 10.1016/0006-2952(83)90585-3. [DOI] [PubMed] [Google Scholar]
  62. Woenne R., Kattan M., Levison H. Sodium cromoglycate-induced changes in the dose-response curve of inhaled methacholine and histamine in asthmatic children. Am Rev Respir Dis. 1979 Jun;119(6):927–932. doi: 10.1164/arrd.1979.119.6.927. [DOI] [PubMed] [Google Scholar]
  63. Young S., Le Souëf P. N., Geelhoed G. C., Stick S. M., Turner K. J., Landau L. I. The influence of a family history of asthma and parental smoking on airway responsiveness in early infancy. N Engl J Med. 1991 Apr 25;324(17):1168–1173. doi: 10.1056/NEJM199104253241704. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES