<p>Sir,</p> <p>Treatment of sulfur mustard (SM) injured patient with pulmonary involvement remains as a challenging issue and almost all of used medications, such as corticosteroid, are conservative treatments. Also, we would like to recommend some medications which it theoretically can be effective on patients with SM lung injuries.</p> <p>At the beginning, we should know what do we expect from medications to do in patients with SM lung injury? The most common findings in these patients were dyspnea and chronic cough with thick sputum, which is concordant with a disorder in small airway such as bronchiolitis obliterans (BO). <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>BO is significantly associated with two pathogenesis; oxidant-antioxidant imbalance and chronic inflammation, although other pathogenesis such as protease dysfunction was weekly recommended for these patients. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Also, it seems that chronic inflammation in these patients relief when the antioxidants supply is enhanced. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Previously, it was approved that N-Acetyl Cysteine (NAC) increase the main anti-oxidant product of lung named glutathione (GSH) in these patients. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>Hence, every therapeutic agent that can enhance cellular anti-oxidant supply may be effective on both of mentioned pathway.</p> <p>Hypertonic saline (HTS), a hyperosmolar sodium chloride solution, which was used for bronchiolitis, especially in children septic shock and sputum induction, was introduced. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>One of the main problems that annoy the SM induced lung injury is dense sputum which is composed of apoptotic cell, thick mucus and various cell products in small airways. Also, nebulization with HTS can dilute this sputum via regulating sodium transport in airways membrane. <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>HTS frequently were used for this propose in similar disorders such as cystic fibrosis. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>Sodium-chloride solution, even in normal osmolarity (0.5%), has an approved effect on respiratory symptoms. <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>Inhalation of HTS improves cilliary function of epithelial cell in which can be useful in these patients. <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>In addition, the anti inflammatory effect of HTS was demonstrated. <sup> <xref ref-type="bibr" rid="ref10">10</xref> </sup>This effect is consonant with the role of glycosaminoglycans and IL-8 in neutrophil chemotaxis and inflammation. In addition, cell membrane potential imbalance due to protein misfolding was recommended as the other pathogenesis of SM injury. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Nebulization of HTS 5% was safely used <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>and can be superior to current therapy for early treatment of SM injured patient with bronchiolitis obliterans.</p> <p>Also, the efficacy of curcumin on the apoptotic pathway (such as JNK and NF-KB) was declared. Curcumin is a derivate of turmeric (Curcuma Longa) a famous Indian herbal medication. It was confirmed that curcumin is effective on inflammation (such as rheumatoid arthritis), antioxidant supply and neoplastic disorders. <sup> <xref ref-type="bibr" rid="ref12">12</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>Likewise, it was clarified that defect in cell repair was introduced as the main cellular mechanism, which justified the SM injury pathogenesis. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>At the same, Li et al. demonstrated that curcumin can affect the TGF-beta/smads signaling pathway in which seriously considered in SM injured patients. <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>Also, curcumin can modulate some inter-cellular signals such as MMP and VEGF, which have considerable role in these patients. <sup> <xref ref-type="bibr" rid="ref16">16</xref> </sup>Fibroblasts via overproduction of collagen and impaired inter-cellular adhering molecule (such as laminin and cathepsin) <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref17">17</xref> </sup>has the main role in SM pathogenesis and likely, curcumin can regulate these cells as well. <sup> <xref ref-type="bibr" rid="ref18">18</xref> </sup>Recently, curcumin was effectively used for late skin lesion of SM. <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>Moreover, it seems that it can be effective on SM induced lung disease because there is some evidence that is confirmed the efficacy of curcumin on airway epithelial cell injured by toxic agents. <sup> <xref ref-type="bibr" rid="ref20">20</xref> </sup></p> <p>Although, TGF-beta regulating medication such as gamma interferon was effectively used in these patients and other anti-inflammatory treatment such as anti cytokines and TNF-alpha antagonist theorically may be effective but we need medications which impress the main pathogenesis pathway. <sup> <xref ref-type="bibr" rid="ref21">21</xref> </sup></p> <p>Another therapeutic option such as vitamin E and proanthocyanidin was sporadically used on patients with SM injury but more study is needed to approve their results. <sup> <xref ref-type="bibr" rid="ref22">22</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref23">23</xref> </sup>On the other hand, using other ways to administrate routine medications e.g. corticosteroids such as chest patch and inhaled spray as nano-particle or micelle (such as chitosan) can be more effective than oral prescription on clinical symptoms, in addition to lower side effects.</p> <p>Finally, it is necessary to find the main etiology of the mustard lung (regarding to the role of TGF-β increases and oxidant-antioxidant imbalances) to find the completely effective treatment for these patients.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ghanei</surname> 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Journal of Research in Medical Sciences

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JRMS-17-1092

23833589

Letter to Editor

Perspective in future pharmacological approach to sulfur mustard lung injuries

Saburi

Amin

Shohrati

Majid

Ghanei

Mostafa

Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Address for correspondence:Mostafa Ghanei, Chemical injuries research center, Baqiyatallah University of medical sciences, mollasadra St, Vanak Sq, Tehran, Iran mghaneister@gmail.com

November 2012

17 11 1092 1093

2012

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<p>Sir,</p> <p>Treatment of sulfur mustard (SM) injured patient with pulmonary involvement remains as a challenging issue and almost all of used medications, such as corticosteroid, are conservative treatments. Also, we would like to recommend some medications which it theoretically can be effective on patients with SM lung injuries.</p> <p>At the beginning, we should know what do we expect from medications to do in patients with SM lung injury? The most common findings in these patients were dyspnea and chronic cough with thick sputum, which is concordant with a disorder in small airway such as bronchiolitis obliterans (BO). <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>BO is significantly associated with two pathogenesis; oxidant-antioxidant imbalance and chronic inflammation, although other pathogenesis such as protease dysfunction was weekly recommended for these patients. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Also, it seems that chronic inflammation in these patients relief when the antioxidants supply is enhanced. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Previously, it was approved that N-Acetyl Cysteine (NAC) increase the main anti-oxidant product of lung named glutathione (GSH) in these patients. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>Hence, every therapeutic agent that can enhance cellular anti-oxidant supply may be effective on both of mentioned pathway.</p> <p>Hypertonic saline (HTS), a hyperosmolar sodium chloride solution, which was used for bronchiolitis, especially in children septic shock and sputum induction, was introduced. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>One of the main problems that annoy the SM induced lung injury is dense sputum which is composed of apoptotic cell, thick mucus and various cell products in small airways. Also, nebulization with HTS can dilute this sputum via regulating sodium transport in airways membrane. <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>HTS frequently were used for this propose in similar disorders such as cystic fibrosis. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>Sodium-chloride solution, even in normal osmolarity (0.5%), has an approved effect on respiratory symptoms. <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>Inhalation of HTS improves cilliary function of epithelial cell in which can be useful in these patients. <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>In addition, the anti inflammatory effect of HTS was demonstrated. <sup> <xref ref-type="bibr" rid="ref10">10</xref> </sup>This effect is consonant with the role of glycosaminoglycans and IL-8 in neutrophil chemotaxis and inflammation. In addition, cell membrane potential imbalance due to protein misfolding was recommended as the other pathogenesis of SM injury. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Nebulization of HTS 5% was safely used <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>and can be superior to current therapy for early treatment of SM injured patient with bronchiolitis obliterans.</p> <p>Also, the efficacy of curcumin on the apoptotic pathway (such as JNK and NF-KB) was declared. Curcumin is a derivate of turmeric (Curcuma Longa) a famous Indian herbal medication. It was confirmed that curcumin is effective on inflammation (such as rheumatoid arthritis), antioxidant supply and neoplastic disorders. <sup> <xref ref-type="bibr" rid="ref12">12</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>Likewise, it was clarified that defect in cell repair was introduced as the main cellular mechanism, which justified the SM injury pathogenesis. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>At the same, Li et al. demonstrated that curcumin can affect the TGF-beta/smads signaling pathway in which seriously considered in SM injured patients. <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>Also, curcumin can modulate some inter-cellular signals such as MMP and VEGF, which have considerable role in these patients. <sup> <xref ref-type="bibr" rid="ref16">16</xref> </sup>Fibroblasts via overproduction of collagen and impaired inter-cellular adhering molecule (such as laminin and cathepsin) <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref17">17</xref> </sup>has the main role in SM pathogenesis and likely, curcumin can regulate these cells as well. <sup> <xref ref-type="bibr" rid="ref18">18</xref> </sup>Recently, curcumin was effectively used for late skin lesion of SM. <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>Moreover, it seems that it can be effective on SM induced lung disease because there is some evidence that is confirmed the efficacy of curcumin on airway epithelial cell injured by toxic agents. <sup> <xref ref-type="bibr" rid="ref20">20</xref> </sup></p> <p>Although, TGF-beta regulating medication such as gamma interferon was effectively used in these patients and other anti-inflammatory treatment such as anti cytokines and TNF-alpha antagonist theorically may be effective but we need medications which impress the main pathogenesis pathway. <sup> <xref ref-type="bibr" rid="ref21">21</xref> </sup></p> <p>Another therapeutic option such as vitamin E and proanthocyanidin was sporadically used on patients with SM injury but more study is needed to approve their results. <sup> <xref ref-type="bibr" rid="ref22">22</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref23">23</xref> </sup>On the other hand, using other ways to administrate routine medications e.g. corticosteroids such as chest patch and inhaled spray as nano-particle or micelle (such as chitosan) can be more effective than oral prescription on clinical symptoms, in addition to lower side effects.</p> <p>Finally, it is necessary to find the main etiology of the mustard lung (regarding to the role of TGF-β increases and oxidant-antioxidant imbalances) to find the completely effective treatment for these patients.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ghanei</surname> 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