Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status

Einat Fireman Klein,1 Yochai Adir,1 Amir Krencel,2 Regina Peri,2 Bella Vasserman,2 Elizabeth Fireman,3,4 Aharon Kessel2 1Pulmonary Division, Carmel Medical Center, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel; 2Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel; 3Institute of Pulmonary Diseases, National Laboratory Service for Interstitial Lung Diseases, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; 4Department of Occupational and Environmental Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Purpose: Ultrafine particles (UFP) are toxic due to their small size and penetration into deeper lung compartments. We aimed to evaluate the exhaled breath condensate (EBC)-UFP content as a reflection of inflammation and oxidative stress status in COPD patients and as an exacerbation risk marker.Methods: EBC was collected by conventional methods. Particles were analyzed with NanoSight LM20. EBC carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA kits. Study population (58 COPD patients and 40 healthy smoker and non-smoker controls) underwent spirometry, diffusion capacity, EBC testing, and blood sampling.Results: Absolute eosinophil count, C-reactive protein (CRP), and lactate dehydrogenase in serum were elevated in the COPD group compared with the controls (224 U/L, 5 mg/L, and 391 U/L vs 154 U/L, 3 mg/L, and 330 U/L, P=0.009, P=0.05, and P=0.004, respectively). COPD patients had lower UFP concentrations in EBC compared with controls (0.24 E8/mL vs 0.51 E8/mL, P≤0.001). A mirror image was detected in serum: COPD patients had higher UFP concentrations compared with controls (9.8 E8/mL vs 6.7 E8/mL, respectively, P=0.03). EBC carbonyl and 8-OHdG levels were higher among COPD patients compared with controls (5.1 per 1 µg/mL protein and 0.036 ng/mL vs 0.41 per 1 µg/mL protein and 0.003 ng/mL, P=0.001 and P≤0.001, respectively). EBC UFP concentrations were negatively correlated with pack years (R=-0.44, P≤0.001) and positively correlated with FEV1 and diffusing lung capacity for carbon monoxide (R=0.46, 0.23, P≤0.001 and P=0.04, respectively). Low EBC UFP concentrations (≤0.18 E8/mL) and CRP levels ≥5 mg/L were independent predictors of the frequent exacerbator phenotype (OR 3.6; 95% CI: 1.06–7.97; P=0.04 and OR 4.4; 95% CI: 1.24–10.2; P=0.02, respectively).Conclusion: UFP content in EBC reflects the inflammatory state of airways. Low UFP concentrations in EBC and high in serum of COPD patients support our hypothesis that increased epithelial permeability could be the mechanism behind those findings. Keywords: exhaled breath condensate, EBC, oxidative stress, COPD