Abstract
Background:
Victims of sulfur mustard (SM) gas exposure experience different types of chronic pulmonary disease, manifested as cough, sputum production, and dyspnea. Conventional therapies (eg, immunosuppressive drugs, corticosteroids) have not been effective in these patients.
Objective:
This study was carried out to determine the efficacy of concomitant administration of the macrolide clarithromycin and the mucolytic agent acetylcysteine in the treatment of bronchiolitis obliterans in SM-exposed patients.
Methods:
This open-label clinical study was conducted at the Research Center of Chemical Injuries, Baqiyatallah Medical Sciences University, Tehran, Iran. Clarithromycin and acetylcysteine were administered concomitantly for 6 months to male SM-exposed patients with chronic bronchitis and bronchiolitis obliterans who were nonresponsive to conventional treatments. Efficacy analysis included symptom assessment and pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio) using spirometry, performed at baseline and after 2 and 6 months of treatment.
Results:
Seventeen male patients (mean [SD] age, 38.3 [5.3] years [range, 31–50 years]; mean [SD] body weight, 77.9 [15.7] kg) were included in the study. Cough and sputum production were each found in 10 of 17 patients (58.8%) at baseline and were improved in all 10 patients after the administration of clarithromycin and acetylcysteine. FEV1 and FVC also were improved, by mean (SD) 10.6% (9.7%) (P < 0.001 vs baseline) and 12.9% (13.6%) (P = 0.001 vs baseline). No significant change in FEV1/FVC ratio was found.
Conclusions:
In this study of concomitant administration of clarithromycin and acetylcysteine for the treatment of bronchiolitis obliterans in SM-exposed patients, symptoms and pulmonary function were improved. These results may have been related to the therapeutic effects of a macrolide antibiotic on chronic bronchitis and bronchiolitis obliterans in these patients. Based on the results of this study, we recommend this treatment for chemical warfare victims with recurrent exacerbation of bronchitis who do not respond to conventional treatment.
Key words: sulfur mustard, chemical warfare, chronic bronchitis, bronchiolitis, clarithromycin, acetylcysteine
Full Text
The Full Text of this article is available as a PDF (469.9 KB).
References
- 1.Cairn J, Yek T, Banner NR. Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2003;22:50–57. doi: 10.1016/s1053-2498(02)00548-x. [DOI] [PubMed] [Google Scholar]
- 2.Fieguth HG, Krueger S, Wiedenmann DE. Tacrolimus for treatment of bronchiolitis obliterans syndrome after unilateral and bilateral lung transplantation. Transplant Proc. 2002;34:1884. doi: 10.1016/s0041-1345(02)03108-1. [DOI] [PubMed] [Google Scholar]
- 3.Fuloria M, Rubin BK. Evaluating the efficacy of mucoactive aerosol therapy. Respir Care. 2000;45:868–873. [PubMed] [Google Scholar]
- 4.Ruffmann R, Wendel A. GSH rescue by N-acetylcysteine. Klin Wochenschr. 1991;69:857–862. doi: 10.1007/BF01649460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.New York Security Council of United Nations (NYSCUN) NYSCUN; Atlanta, Ga: 1986. (Report of specialists appointed by the secretary general to investigate allegations by the Islamic Republic of Iran concerning the use of chemical weapons). Document no. S/16433/1986. [PubMed] [Google Scholar]
- 6.Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: Analysis of 197 cases. Chest. 1997;112:734–738. doi: 10.1378/chest.112.3.734. [DOI] [PubMed] [Google Scholar]
- 7.Thomason JW, Rice TW, Milstone AP. Bronchiolitis obliterans in a survivor of a chemical weapons attack. JAMA. 2003;290:598–599. doi: 10.1001/jama.290.5.598. [DOI] [PubMed] [Google Scholar]
- 8.Ghanei M, Mokhtari M, Mir Mohammad M, Aslani J. Bronchiolitis obliterans following exposure to sulfur mustard: Chest high resolution computed tomography. Eur J Radiol. 2004;52:164–169. doi: 10.1016/j.ejrad.2004.03.018. [DOI] [PubMed] [Google Scholar]
- 9.Laohaburanakit P, Chan A, Allen RP. Bronchiolitis obliterans. Clin Rev Allergy Immunol. 2003;25:259–274. doi: 10.1385/CRIAI:25:3:259. [DOI] [PubMed] [Google Scholar]
- 10.Chan A, Allen R. Bronchiolitis obliterans: An update. Curr Opin Pulm Med. 2004;10:133–141. doi: 10.1097/00063198-200403000-00008. [DOI] [PubMed] [Google Scholar]
- 11.American Thoracic Society Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995;152:1107–1136. doi: 10.1164/ajrccm.152.3.7663792. [DOI] [PubMed] [Google Scholar]
- 12.Boman G, Bäcker U, Larsson S. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: Report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis. 1983;64:405–415. [PubMed] [Google Scholar]
- 13.Long-term oral acetylcysteine in chronic bronchitis. A double-blind controlled study. Eur J Respir Dis. 1980;111:93–108. (Suppl) [PubMed] [Google Scholar]
- 14.Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: A meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther. 2000;22:209–221. doi: 10.1016/S0149-2918(00)88479-9. [DOI] [PubMed] [Google Scholar]
- 15.van Schayck CP, Dekhuijzen PN, Gorgels WJ. Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis. Respir Med. 1998;92:1259–1264. doi: 10.1016/s0954-6111(98)90225-6. [published correction appears in Respir Med. 1999;93:224] [DOI] [PubMed] [Google Scholar]
- 16.Spiritue E, Devcich K, Dmec J, Hallwae R. Clarithromycin vs. cefaclor for acute bacterial exacerbations of bronchitis. Proceedings of the First International Conference on the Macrolides, Azalides, and Streptogramine; Santa Fe, New Mexico; January 1992. Abstract 239. [Google Scholar]
- 17.Aldons PM. A comparison of clarithromycin with ampicillin in the treatment of outpatients with acute bacterial exacerbation of chronic bronchitis. J Antimicrob Chemother. 1991;27(Suppl A):101–108. doi: 10.1093/jac/27.suppl_a.101. [DOI] [PubMed] [Google Scholar]
- 18.Anzueto A, Jenkinson SG, for the Clarithromycin Chronic Bronchitis Study Group Safety and efficacy of clarithromycin vs cefuroxime axetil in the treatment of acute bacterial exacerbation of chronic bronchitis. Immunol Infect Dis (Oxford) 1993;3:231–237. [Google Scholar]
- 19.Bachand RT., Jr Comparative study of clarithromycin and ampicillin in the treatment of patients with acute bacterial exacerbations of chronic bronchitis. J Antimicrob Chemother. 1991;27(Suppl A):91–100. doi: 10.1093/jac/27.suppl_a.91. [DOI] [PubMed] [Google Scholar]
- 20.Guay DR, Craft JC. Comparative safety and efficacy of clarithromycin and ampicillin in the treatment of out-patients with acute bacterial exacerbation of chronic bronchitis. J Intern Med. 1992;231:295–301. doi: 10.1111/j.1365-2796.1992.tb00538.x. [DOI] [PubMed] [Google Scholar]
- 21.Neu HC, Chick TW. Efficacy and safety of clarithromycin compared to cefixime as outpatient treatment of lower respiratory tract infections. Chest. 1993;104:1393–1399. doi: 10.1378/chest.104.5.1393. [DOI] [PubMed] [Google Scholar]
- 22.Tamaoki J, Takeyama K, Tagaya E, Konno K. Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother. 1995;39:1688–1690. doi: 10.1128/aac.39.8.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Tamaoki J, Sakai N, Tagaya E, Konno K. Macrolide antibiotics protect against endotoxin-induced vascular leakage and neutrophil accumulation in rat trachea. Antimicrob Agents Chemother. 1994;38:1641–1643. doi: 10.1128/aac.38.7.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Ras GJ, Anderson R, Taylor GW. Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosa pigments with human neutrophils in vitro. Antimicrob Agents Chemother. 1992;36:1236–1240. doi: 10.1128/aac.36.6.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Dompeling E, Jobsis Q, Vandevijver NM. Chronic bronchiolitis in a 5-year-old child after exposure to sulphur mustard gas. Eur Respir J. 2004;23:343–346. doi: 10.1183/09031936.04.00100004. [DOI] [PubMed] [Google Scholar]
