Highly sensitive C-reactive protein levels in Iranian patients with pulmonary complications of sulfur mustard poisoning & its correlation with severity of airway diseases S. M.Lari, D. Attaran, M. Towhidi, Lung Disease & Tuberculosis Research Center Mashhad University of Medical Sciences

Background Sulfur mustard(SM) is a potent, toxic, alkylating agent that is able to cause serious ocular, neurologic, cutaneous, bone marrow, and pulmonary complications. The most common late complications of SM poisoning are respiratory problems. “Mustard Lung” as, a unique form of chronic obstructive pulmonary disease in patients with late respiratory complication of sulfur mustard poisoning*. *. Ghanei M., et al. Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian "mustard lung" patients. Mil Med 2007; 172: 70-74.

Background Highly sensitive C-reactive protein (hs-CRP) is one of the important inflammatory markers that is synthesized by hepatocytes during inflammatory reactions. In the last decade, concern has grown about significant correlations of hs-CRP with myocardial infarction, unstable angina, and stroke.

Background It is now believed that chronic obstructive pulmonary disease (COPD) is a systemic condition that inflammatory markers ( hs-CRP, IL-6,…) have important roles in its pathogenesis. Recent studies have shown that serum level of hs-CRP is elevated both in stable & exacerbation states of COPD and is related to lower FEV1. Also, hs-CRP is a strong and independent predictor of future COPD outcome.

Aim The present study is the first, of which we are aware, that was designed to determine serum highly sensitive C- reactive protein and evaluate its correlation with lung function parameters in patients with chronic obstructive pulmonary disease due to SM poisoning.

Methods and Materials Between April and September 2008, all the chemical war gassed veterans with stable COPD who attended to the pulmonary clinic of Ghaem hospital, in Mashhad, Iran, were entered into this current cross- sectional study. All patients had validated documents of sulfur mustard gas exposure and suffered from complications of sulfur mustard poisoning. Also 30 nonsmoker, healthy men were enrolled into this study as a control group and their age and body mass index (BMI) were matched to the subjects.

Inclusion criteria post-bronchodilator FEV1/FVC < 0.7 after 400 µg of inhaled albuterol validated documents of sulfur mustard gas exposure and suffered from complications of sulfur mustard poisoning Non-smoking

Exclusion Criteria If their FEV1 increased more than 12% and 200 ml after bronchodilator If they had asthma , bronchiectasis, tuberculosis , active pulmonary infections, cardiovascular diseases, diabetes mellitus or other confounding inflammatory diseases, such as malignancy, arthritis, connective tissue diseases, and inflammatory bowel disease; If they had exacerbation of disease or hospitalization during the last 2 months. Those patients who had taken aspirin, statins were excluded.

Methods & Material One chest physician visited all the subjects and the following items were recorded: BMI SGRQ Spirometry MMRC scale 6MWT ABG Blood sample for hs-CRP

Results The mean serum hs-CRP levels were significantly higher in the patients than in the controls (9.4 ± 6.78 SD versus 3.9 ±1.92 SD mg/l, p<0.001). Out of 50 patients in the case group, 32 (64%) had high serum hs-CRP levels (≥ 5 mg/l).

Clinical and pathophysiological parameters of 50 patients with mustard lung Values Clinical & Pathophysiological parameters 46.3± 9.18 Age (yrs) 17.00± 6.00 Duration of disease(yrs) 58.98±17.51 FEV1(%Pred.) 62.14±9.70 FEV1/FVC 327.8±86.96 6MWD(m) 27.32 ± 3.30 BMI 75.1 ± 12.00 PaO2(mmHg) 94.03 ± 3.45 SaO2(%) 45.37±9.50 PaCo2(mmHg) 56.23 ± 14.31 Total SGRQ Score 9.40±6.78 hs-CRP(mg/l) 42% Inhaled corticosteroid therapy ( % of patients)

Frequency of GOLD staging in patients

Correlation of hs-CRP & GOLD satges

Correlations between hs-CRP and FEV-1

BODE Index Celli BR, et al. The Body-Mass Index, Airflow Obstruction, Dyspnea , Exercise Capacity Index in Chronic Obstructive Pulmonary Disease. NEJM 2004; 350:1005-1012.

Correlation of hs-CRP with lung function parameters P value Correlation Coefficient(r) Variable 0.71 0.06 Age 0.056 0.27 BMI 0.60 0.082 Duration of disease 0.010 -0.32 FEV1 0.001 0.45 GOLD 0.70 -0.06 PaO2 0.009 0.37 PaCo2 0.330 0.07 BODE 0.85 0.2 Total SGRQ score

Conclusion The present study demonstrates that chronic lung disease in patients with respiratory complication of SM poisoning is associated with systemic inflammation and that level of inflammatory markers (hs-CRP) is correlated with the severity of airway disease. Serum hs-CRP significantly correlates with GOLD, FEV1, FEV1 percent predicted, and PaCo2.

Conclusion In this study we found that, despite the exclusion of smoking, cardiovascular diseases, infections, and other important inflammatory conditions, hs-CRP levels are raised in SM patients and that significant differences in the mean hs-CRP levels exist between patients and controls . Hs-CRP may have an important role as an inflammatory marker of disease severity in mustard lung patients as it does in other COPD patients.

Thank You larish851@mums.ac.ir