Background: The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard gas. Pulmonary complications as a result of this gas range from severe bronchial stenosis to mild or no symptoms. Airway hyperresponsiveness (AHR) which is usually assessed as response to inhaled methacholine is the most characteristic feature of asthma. AHR is reported in chronic obstructive pulmonary disease patients and smokers, and may also show in chemical warfare victims. However, there are little reports regarding AHR in chemical warfare victims. Objective: Therefore, in this study, airway responsiveness to methacholine in victims of chemical warfare was examined. Methods: The threshold concentrations of inhaled methacholine required for a 20% change in forced expiratory flow in 1 s (FEV1; PC20) or a 35% change in specific airway conductance (PC35) were measured in 15 chemical war victims and 15 normal control subjects. Results: In 10 out of 15 chemical warfare victims (two thirds), PC20 and PC35 methacholine could be measured and subjects were called responders. AHR to methacholine in responder chemical war victims (PC20 = 0.41 and PC35 = 0.82 g/l) was significantly lower than in normal subjects (PC20 = 5.69 and PC35 = 4.60 g/l, p < 0.001 for both cases). There was a significant correlation between FEV1 and PC20 methacholine (r = 0.688, p < 0.001). The correlations between PC20 and PC35 were statistically significant as well (r = 0.856, p < 0.001). Conclusion: Results showed increased airway responsiveness of most chemical warfare victims to methacholine which correlated with the FEV1 value and which may be related to chronic airway inflammation or irreversible airway changes.

1.
Dacre JC, Goldman M: Toxicology and pharmacology of the chemical warfare agent sulfur mustard. Pharmacol Rev 1996;48:289–326.
2.
Evison D, Hinsley D, Rice P: Chemical weapons. Br Med J 2002;324:332–335.
3.
Bahadori M, Pishva N, Masjedi MR: History of pulmonary lesions in victims of chemical warfare. Ir J Med Sci 1989;14:999–1005.
4.
Emad AF, 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.
5.
Emad AF, Rezaian GR, Hoseini K, Ghayyoomi SMA: Chronic pulmonary sequelae of sulfur mustard exposure in man. A report of 36 cases. Ir J Med Sci 1995;20:1–4.
6.
Briton JR, Burney PG, Chinn S, Paracosta A, Tattersfield AE: The relationship between change in airway reactivity and change in respiratory symptoms and medication in a community study. Am Rev Respir Dis 1988;138:530–534.
7.
Ramsdale EH, Morris MM, Roberts RS, Hargreave FE: Methacholine bronchial responsiveness in chronic bronchitis: Relationship to airflow obstruction and cold air responsiveness. Thorax 1994;39:912–918.
8.
Frew AJ: Advances in environmental and occupational disorders. J Allergy Clin Immunol 2003;111:S824–S828.
9.
Padrid P, Snook S, Finucane T, Shiue P, Cozzi P, Solway J, Leff AR: Persistent airway hyperresponsiveness and histologic alteration after chronic antigen challenge in cats. Am J Respir Crit Care 1995;151:184–193.
10.
Mapp CE, Boniotti A, Papi A, et al: The effect of phosphoramidon and epithelial removal on toluene diisocyanate-induced contraction in guinea pig bronchi. Eur Respir J 1992;5:331–333.
11.
Trigg CJ, Bennett JB, Tooly M, Sibbald B, D’Souza MF, Davis RJ: A general practice based survey of bronchial hyperresponsiveness and its relations to symptoms, sex, age, atopy and smoking. Thorax 1990;45:866–872.
12.
Gillett MK, Snashall PD: Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects. Eur Respir J 1988;1:27–33.
13.
American Thoracic Society: Standardization of spirometry, 1994 update. Official Statement of American Thoracic Society. Am J Respir Crit Car Med 1995;152:1107–1136.
14.
Willems JL: Clinical management of mustard gas casualties. An Med Milit 1989;3(suppl):1–61.
15.
Assennato G, Ambrosi F, Sivo D: Possible respiratory long-term effects of yperite exposure in fishermen. Med Lav 1997;88:148–154.
16.
Hosseini K, Moradi A, Mansouri A, Vesal K: Pulmonary manifestations of mustard gas injury: A review of 61 cases. Ir J Med Sci 1989;14:20–25.
17.
Emad A, Rezaian GR: Immunoglobulins and cellular constituents of the BAL. Chest 1999;115:1346–1351.
18.
Sohrabpour H: The current status of mustard gas victims in Iran. ASA Newslett 1995;95:14–15.
19.
Heidarinejad H, Zendedel N, Dastgerdi S: Temporal trend of clinical and spirometric parameters in mustard gas victims; A ten years study. Arch Ir Med 1998;1:13–16.
20.
Freitag L, Firusian N, Stramatis G, et al: The role of bronchoscopy in pulmonary complications due to mustard gas inhalation. Chest 1991;100:1436–1441.
21.
Zarchi K, Akbar A, Naieni KH: Long-term pulmonary complications in combatants exposed to mustard gas: A historical cohort study. Int J Epidemiol 2004;33:579–581.
22.
Hosseini K, Alavi S, Abedi AI: Reversibility of airflow obstruction in chronic obstructive pulmonary disease, secondary to sulfur mustard gas injury. Arch Ir Med 1999;2:178–180.
23.
Boskabady MH, Snashall PD: Bronchial responsiveness to beta-adrenergic stimulation and enhanced beta-blockade in asthma. Respirology 2000;5:111–118.
24.
Boskabady MH, Saadatinejad M: Airway responsiveness to beta-adrenergic agonist (salbutamol) in asthma. J Asthma 2003;40:917–925.
25.
Calvet JH, Jarreau PH, Levame M, D’Ortho MP, Lorino H, Harf A, Macquin-Mavier I: Acute and chronic respiratory effects of sulfur mustard intoxication in guinea pig. J Appl Physiol 1994;76:681–688.
26.
Brooks SM, Weiss MA, Bernstein IL: Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest 1985;88:376–384.
27.
Aizawa H, Shigyo M, Matsumoto K, Inoue H, Koto H, Hara N: PACAP reverses airway hyperresponsiveness induced by ozone exposure in guinea pigs. Respiration 1999;66:538–542.
28.
Booth H, Richmond I, Ward C, Gardiner PV, Harkawat R, Walters HE: Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. Am J Respir Crit Care Med 1995;152:45–52.
29.
Calvet JH, Coste A, Levame M, Harf A, Macquin-Mavier I, Escudier E: Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of glucocorticoids. Hum Exp Toxicol 1996;15:964–971.
30.
Calvet JH, Gascard JP, Delamanche S, Brink C: Airway epithelial damage and release of inflammatory mediators in human lung parenchyma after sulfur mustard exposure. Hum Exp Toxicol 1999;18:77–81.
31.
Calvet JH, Planus E, Rouet P, Pezet S, Levame M, Lafuma C, Harf A, D’Ortho MP: Matrix metalloproteinase gelatinases in sulfur mustard-induced acute airway injury in guinea pigs. Am J Physiol 1999;276:L754–L762.
32.
Calvet JH, D’Ortho MP, Jarreau PH, Levame M, Harf A, Macquin-Mavier I: Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P. J Appl Physiol 1994;77:2325–2332.
33.
Boskabady MH, Snashall PD: Enhanced muscarinic receptor blockade with atropine in the asthmatic tracheobronchial tree: Evidence for increased drug delivery in asthma. Am Rev Respir Dis 1992;145:756–761.
34.
Sterk PG, Bel EH: Bronchial hyperresponsiveness. The need for a distinction between hypersensitivity and excessive airway narrowing. Eur Respir J 1989;2:267–274.
35.
Farhadi H, Boskabady MH: Airway responsiveness to beta-adrenergic agonists in smokers. Tur Respir J 2003;4(suppl 1):151s.
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