<p>Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status</p>

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 FEV 1 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.

Cigarette-related cadmium and environmental pollution exposure are reflected in airway ultrafine particle content

“…A portable condenser (TURBODECCS, ItalChill, Parma, Italy) was used as described in detail elsewhere [ 14 ]. Briefly, subjects breathed into a collecting system for 5 min at normal tidal volume.…”

“…The size and concentration of the particles was assessed in EBC and serum samples with the NanoSight LM20 system (NanoSight Ltd., Salisbury, UK) [ 14 ]. Briefly, the Brownian motion of particles in the range of 10–1000 nm was captured by the camera.…”

“…Occupational exposure to inhaled toxic chemicals, such as beryllium, chromium, silica and lead, can be detected and monitored using induced sputum and EBC techniques [ 10 – 13 ]. UFPs in EBC were reported to reflect airway inflammation levels and serve as a novel marker of exacerbation risk in COPD [ 14 ]. Moreover, a major toxic effect of inhaled UFP is related to their large surface area, which enables transmission and absorption of hazardous materials, such as heavy metals [ 15 ].…”

“…While the other metals have several other sources, the single-most important source of cadmium is tobacco smoke [ 17 ]. We had earlier shown increased epithelial permeability, as reflected in low concentrations of UFP in EBC, that was due to the inflammatory state of airways [ 14 ]. Our next step was to evaluate the cigarette smoke-related heavy metal content in EBC in the same population of COPD patients.…”

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate

“…After reading these studies, eight were included into the narrative description and six into quantitative synthesis. The study by (Fireman Klein et al 2019) was excluded because only the arithmetic mean was reported -no variability (SD GSD, IC IQR) indicated. The control group in (Pelclova et al 2016b) and in (Pelclova et al 2016c) was identical and was therefore not included twice.…”