LEVEL OF INTERLEUKIN-6 IN STABLE COPD PATIENTS USING THE EXHALED BREATH CONDENSATE

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease that is associated with high morbidity and mortality rates. Interleukin 6 is a proinflammatory cytokine that can be used as a marker of COPD treatment. We conducted a cross-sectional study involving 83 stable COPD patients at X Jakarta Hospital, mostly male (90,4%) with mean ages was 66,07 years. Patients were interviewed using the CAT and mMRC scoring. Patients also underwent a spirometry and had their condensed breaths collected using a device made of a S-shaped glass tube that was immersed in a thermos filled with ice cubes and collected for ELISA examination. This study result was IL-6 detected in 76 patients (91,56%) with mean level of IL-6 was 0,702 pg/ml ± 0,41 pg/ml. We conclude that IL-6 levels from exhaled breaths of stable COPD patients can be collected using a condensation exhalation device and can be recommended as biomarkers of successful treatment of COPD.

exacerbated COPD and their levels increased with increasing degrees of COPD compared to the control group (El-shimy et al., 2014).Evaluation of changes in forced expiratory volume (FEV1) within one second by spirometry in COPD patients can only evaluate therapeutic interventions with bronchodilators but is not specific, hence the use of exhaled breath condensation tests to assess levels of inflammatory cytokines in the airways of COPD patients is useful for evaluating pathway-targeted COPD treatment that was targeted in the pathway of inflammatory process (Chhabra, 2012).
Assessment of cytokines in COPD patients in previous studies used more invasive methods with blood plasma samples, sputum induction and bronchial rinses.The exhaled breath condensation test is a non-invasive method, but the use of this tool to assess levels of inflammatory cytokines in COPD patients like IL-6 has never been studied, so researchers are interested using the exhaled breath condensation test to assess cytokine levels in stable COPD patients.

METHOD
This research was a cross sectional study with a descriptive analytic method.The research was conducted at the Asthma-COPD Policlinic of X Primary data were obtained from interviews and questionnaires that had been prepared and patients also underwent a spirometry examination (CHEST Spirometry) and their spirometry data was taken, we also collected exhaled breath condensation test samples using a S-shaped glass tube that was immersed in a thermos filled with ice cubes and then the sample obtained will be carried out with an ELISA examination in the IMERI laboratory to measure IL-6 level.The design and method of the device and collection were adjusted based on research by Vyas, et al in 2012 (Figure 1) (Vyas et al., 2012).

RESULT AND DISCUSSION
During the study period from January 2019 to  In this study, of the 83 subjects, as many as 76 (91,56%) subjects was detected IL-6 levels by the ELISA method.IL-6 levels from 76 subjects, the mean level was 0.702 pg / mL ± 0.416.The mean levels of IL-6 level by COPD group showed in table 2 and IL-6 cytokine levels detected in stable COPD subjects according to the degree of COPD group (Graphic 1).Interleukin 6 plays a role in systemic inflammation in COPD.Overexpression of IL-6 also causes emphysema and airway inflammation.Therefore, IL-6 is an important biomarker in COPD (Sin and Man, 2008).This study has limitations, namely that healthy subjects who are not COPD are not included in the study, so that the baseline value of the cytokines IL-6 levels of healthy subjects were not obtained.

CONCLUSION AND SUGGESTIONS
From this study, the exhaled breath condensation test can be used to detect cytokine levels in stable COPD by group with ELISA examination.In this study, IL-6 levels can be used for monitoring therapy and as a therapeutic target in stable COPD patients.Further studies are needed in healthy subjects without COPD to determine the cut off point value of cytokine IL-6 levels in healthy patients with stable COPD patients.In future studies, it should be done completely in stable COPD without comorbidities in the lungs.

Figure 1 .
Figure 1.Exhaled breath condensation device (Vyas et al., 2012) Samples were obtained by means of consecutive sampling until the minimum number of samples was met.Data analysis using SPSS 18 which then a normality test was performed using the Kolmogorov-Smirnov test with p value> 0.05 and homogeneity test with Levene's test with p value <0.05, to obtain IL-6 level data was homogeneous.

Figure 2 .
Figure 2. Detectable levels of IL-6 by COPD Group in Persahabatan Hospital

Scatter plot image of IL-6 levels by the degree of stable COPD group
Sin et al. in their article states that in a stable COPD condition IL-6 plays a role in the increase in levels of CRP, fibrinogen, leukocytes and blood platelets compared to healthy control patients.