S. M.Lari, D. Attaran, M. TowhidiS. M.Lari, D. Attaran, M. Towhidi,,

Lung Disease & Tuberculosis Research CenterLung Disease & Tuberculosis Research Center

Mashhad University of Medical SciencesMashhad University of Medical Sciences

Highly sensitive C-reactive protein levels in Highly sensitive C-reactive protein levels in Iranian patients with pulmonary Iranian patients with pulmonary

complications of sulfur mustard poisoning & complications of sulfur mustard poisoning & its correlation with severity of airway diseasesits correlation with severity of airway diseases

• 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*.

Background

*. 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.

• 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.

Background

• 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.

AimAim

• 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.

Methods and Materials

• 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

Inclusion 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.

Exclusion CriteriaExclusion Criteria

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

Methods & MaterialMethods & Material

• 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).

ResultsResults

Clinical and pathophysiological parameters Clinical and pathophysiological parameters of 50 patients with mustard lungof 50 patients with mustard lung

Clinical & Pathophysiological parametersValues

Age (yrs)46.3± 9.18

Duration of disease(yrs)17.00± 6.00

FEV1(%Pred.)58.98±17.51

FEV1/FVC62.14±9.70

6MWD(m)327.8±86.96

BMI27.32 ± 3.30

PaO2(mmHg)75.1 ± 12.00

SaO2)%(94.03 ± 3.45

PaCo2(mmHg)45.37±9.50

Total SGRQ Score56.23 ± 14.31

hs-CRP(mg/l)9.40±6.78

Inhaled corticosteroid therapy ( % of patients) 42%

Frequency of GOLD staging in patientsFrequency of GOLD staging in patients

Correlation of hs-CRP & GOLD satgesCorrelation of hs-CRP & GOLD satges

Correlations between hs-CRP and FEV-1Correlations between hs-CRP and FEV-1Correlations between hs-CRP and FEV-1Correlations between hs-CRP and FEV-1

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

BODE IndexBODE Index

Correlation of hs-CRP with lung function Correlation of hs-CRP with lung function parametersparameters

VariableCorrelation Coefficient(r)P value

Age0.060.71

BMI0.270.056

Duration of disease0.0820.60

FEV1-0.320.010

GOLD0.450.001

PaO2-0.060.70

PaCo20.370.009

BODE0.070.330

Total SGRQ score0.20.85

ConclusionConclusion

• 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.

ConclusionConclusion

• 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