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

Abstract

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: COPD; EBC; exhaled breath condensate; oxidative stress.

Figure 1

UFP concentration in exhaled breath condensate (A) and serum (B) of COPD patients and healthy controls. Notes: *P ≤0.05. The differences between the COPD patients and the healthy controls were gender-and age-adjusted. Abbreviation: UFP, ultrafine particles.

Figure 2

Frequent exacerbator phenotype risk (≥2/1 with hospitalization per year). Abbreviations: CAT, COPD assessment test; CRP, C-reactive protein; EBC, breath condensate; Periph EOS, peripheral eosinophils.

Figure 3

Carbonyl (A) and 8-OHdG (B) levels in exhaled breath condensate of the COPD patients and the healthy controls. Note: **P ≤0.01.