Exhaled Breath Condensate Containing Ultrafine Particles Marks COPD Damage

A recent study measured exhaled breath condensate (EBC) content containing ultrafine particles (UFP) as a reflection of inflammation and oxidative stress in patients with chronic obstructive pulmonary disease (COPD) and as a marker of exacerbations. The researchers said their findings are the first step in the establishment of the EBC-UFP content as an airway inflammation marker.

The toxic effect of UFP is related to their large surface area, small size, and high penetration rate into deeper lung compartments, characteristics that work separately from the particles' chemical properties. Oxidant injury of the airway epithelium plays a significant role in UFP-induced toxicity

Although smoking is still considered the primary risk factor for developing COPD, air pollution plays a role, as do other environmental exposures and various individual factors, including genetics, airway hyper-responsiveness, and reduced baseline lung function in early adulthood.

Other studies have demonstrated that respiratory symptoms and airway inflammation are correlated with UFP content in the EBC of children with asthma. The concept of oxidative stress biomarkers in EBC supports the idea of personalized medicine as part of optimal surveillance and management

of COPD.

EBC is a simple and noninvasive tool that involves the collection of exhaled air into a cooled tube. The fluid that is condensed from the exhaled breath contains substances from small- and medium-sized airways, which can be assessed for inflamma­tory and oxidative stress biomarkers.

This study involved 58 patients with COPD and 40 healthy smoker and non-smoker controls. Participants had spirometry, diffusion capacity, EBC testing, and blood sampling. EBC was collected by conventional methods. Particles were analyzed with Nano Sight LM20. EBC carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA kits.

The results showed that 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 = .009, P = .05, and P = .004, respectively).

Patients with COPD had lower UFP concentrations in EBC compared with controls (0.24 E8/mL vs 0.51 E8/mL, P ≤.001). A mirror image was detected in serum: patients with COPD 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 patients with COPD 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 ≤.001, respectively).

EBC UFP concentrations were negatively correlated with pack years (R = -0.44, P ≤ .001) and positively correlated with forced expiratory volume in 1 second and diffusing lung capacity for carbon monoxide (R=0.46, 0.23, P ≤.001 and P = .04, respectively).

Low EBC UFP concentrations (≤.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).

The researchers said that UFP content in EBC reflects the inflammatory state of airways. Low UFP con­centrations in EBC and high in serum of COPD patients support the idea that increased epithelial permeability could be the mechanism behind those findings.

The advantage of finding a biomarker is that it reflects the local inflammation state of the lung with little or no influence of systemic inflammatory conditions.

Further studies are needed to validate the findings, the researchers said.

Reference

Fireman Klein E, Adir Y, Krencel A, et al. Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status [published online, March 1, 2019]. Int J Chron Obstruct Pulmon Dis. https://doi.org/10.2147/COPD.S187560.