Long Term Follow-Up of Sulfur Mustard Related Bronchiolitis Obliterans Treatment
AbstractBronchiolitis obliterans (BO) is the most remarkable pulmonary sequels of war-related sulfur mustard inhalation. There is little if any data about long-term efficacy of associated BO treatment. Five years spirometric records of three groups of patients with obstructive pulmonary diseases (asthma, COPD, BO) and documented sulfur mustard inhalation were evaluated. The BO patients were treated with inhaled Seretide 125-250/25 (2 puffs BID), azithromycin (250 mg, three times/week) and N-acetylcysteine (1200-1800/day). Asthma and COPD patients were treated according to existing guidelines. Seventy-three (38 asthma, 16 COPD and 19 BO) patients completed the 5 years follow-up. Basal and final FEV1 in BO patients (2.69±0.81 and 2.39±0.65 respectively) were not significantly different from COPD patients (2.46±0.56 and 1.96±0.76 respectively). There was also no significant difference between the yearly FEV1 decline in BO patients compared to COPD patients (60±84 cc vs. 99±79 cc respectively, P=0.163). The non-significant difference of FEV1 decline in BO compared to COPD patients suggests the effectiveness of azithromycin, inhaled steroid and N-acetyl cysteine in BO patients. Considering safety and possible effectiveness, this treatment is recommended until more data is available from controlled clinical studies.
Emad A, Rezaian GR. The diversity of effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: Analysis of 197 cases. Chest 1997;112:734-8.
Abtahi H, Tehrani MMA, Gohari-Moghaddam K.Chronic respiratory effects of war-related sulfur mustard gas inhalation. Eur Respir J 2007;30:732s-3s.
Ghanei M, Tazelaar HD, Chilosi M, Harandi AA, Peyman M, Akbari HM, et al. An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients. Respir Med 2008;102:825-30.
Ghanei M, Mokhtari M, Mohammad MM, and Aslani J.Bronchiolitis obliterans following exposure to sulfur mustard: Chest high resolution computed tomography. Eur J Radiol 2004;52:164-9.
Hefazi M, Attaran D, Mahmoudi M, Balali-Mood M. Late respiratory complications of mustard gas poisoning in Iranian veterans. Inhal Toxicol 2005;17:587-59.
King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, et al. Constrictive Bronchiolitis in Soldiers Returning from Iraq and Afghanistan. N Engl J Med 2011;365:222-30.
Boehler A, Estenne M. Post-transplant bronchiolitis obliterans. Eur Respir J 2003;22:1007-18.
Vanaudenaerde BM, Meyts I, Vos R, Geudens N, Wever WD, Verbeken1 EK, et al. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J 2008;32:832-43.
Soubani AO and Uberti JP. Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J 2007;29:1007-19.
Khalid M, Saghir AA, Saleemi S, Dammas SA, Zeitouni M, Mobeireek AA, et al. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study. Eur Respir J 2005;25:490-3.
Ghanei M, Abolmaali K, Aslani J. Efficacy of concomitant administration of clarithromycin and acetylcysteine in bronchiolitis obliterans in seventeen sulfur mustard-exposed patients: an open-label study. Curr Ther Res Clin Exp 2004;65:495-504.
Gao X, Ray R, Xiao Y, Ishida K, Ray P. Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes. Pulm Pharmacol Ther 2010;23:97-106.
Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL. Sulfur mustard-induced pulmonary injury: Therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther 2011;24:92-9.
Shohrati M, Aslani J, Eshraghi M, Alaedini F, Ghanei M.Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: Evaluating clinical aspect in patients with impaired pulmonary function test. Respir Med
Ghanei M, Shohrati M, Jafari M, Ghaderi S, Alaeddini F, Aslani J. N-Acetylcysteine Improves the clinical conditions of mustard gas exposed patients with normal pulmonary function test. Basic Clin Pharmacol Toxicol 2008;103:428-32.
Bobb AJ, Arfsten DP, Jederberg WW. N-acetyl-l-cysteine as prophylaxis against sulfur mustard. Mil Med 2005;170:52-6.
Kumar Om, Sugendran K, Vijayaraghavan R. Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes. Chem-Biol Interact 2001;134:1-12.
Ghanei M, Shohrati M, Amini Harandi A, Eshraghi M, Aslani J, Alaeddini F, Manzoori H. Inhaled corticosteroids and long-acting β2-agonists in treatment of patients with chronic bronchiolitis following exposure to sulfur mustard. Inhal Toxicol 2007;19:889-94.
King TE. Bronchiolitis in adults. (Accessed March 24,2016, at http://www.uptodate.com).
GINA Report: Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA),2007. (Accessed March 24, 2016, http://www.ginasthma.com/Guidelineitem.asp?l1=2&l2=1&intId=60).
Pauwels, RA, Buist, AS, Calverley, PM, Jenkins, CR, Hurd, SS, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163:1256-76.
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry, Eur Respir J 2005;26:319-38.
Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D.Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. J Occup Environ Med 2003;45:1136-43.
Ryu JH, Myers JL, Swensen SJ. Bronchiolar Disorders.Am J Respir Crit Care Med 2003;168:1277-92.
Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89.
Soriano JB, Sin DD, Zhang X, Camp PG, Anderson JA, Anthonisen NR, et al. A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo. Chest 2007;131;682-89.
Emad A, Emad Y. CD4/CD8 ratio and cytokine levels of the BAL fluid in patients with bronchiectasis caused by sulfur mustard gas inhalation. J Inflamm 2007;4:2.
Attaran D, Lari SM, Khajehdaluee M, Ayatollahi H, Towhidi M, Asnaashari A, et al. Highly sensitive C- reactive protein levels in Iranian patients with pulmonary complication of sulfur mustard poisoning and its correlation with severity of airway diseases. Hum Exp Toxicol 2009;28:739-74.
Kerstjens HA, Rijcken B, Schouten JP, Postma DE.Decline of FEV1 by age and smoking status: facts,figures, and fallacies. Thorax 1997;52:820-7.
Jensen SP, Lynch DA, Brown KK, Wenzel SE, Newell JD. High-resolution CT features of severe asthma and bronchiolitis obliterans; Clin Radiol 2002;57:1078-85.