Discriminative potential of exhaled breath condensate biomarkers with respect to chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. METHODS: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. RESULTS: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. CONCLUSIONS: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future.

Long-term exposure to PM10 and respiratory health among Parisian subway workers.

Exposure to ambient PM10 may increase the risk of chronic obstructive pulmonary disease (COPD) and lung function decline. We evaluated the long-term exposure to PM10 and its relationship with COPD prevalence and lung function in Parisian subway workers. Participants were randomly selected from a 15,000-subway worker cohort. Individual annual external exposure to PM10 (ePM10) was estimated using a company-specific job-exposure-matrix based on PM10 measurements conducted between 2004 and 2019 in the Parisian subway network. Mean annual inhaled PM10 exposure (iPM10) was modeled as function of ePM10 exposure, inhalation rate, and filtration efficiency of the respiratory protection used. COPD diagnosis was performed in March-May 2021 based on post-bronchodilator spirometry. The relationship between iPM10 and outcomes was assessed using logistic and linear regression models, adjusted for exposure duration and potential confounders. Amongst 254 participants with complete data, 17 were diagnosed as COPD. The mean employment duration was 23.2 ± 7.3years, with annual mean ePM10 of 71.8 ± 33.7 µg/m3 and iPM10 of 0.59 ± 0.27 µg/shift, respectively. A positive but statistically non-significant association was found for COPD prevalence with iPM10 (OR = 1.034, 95%-CI = 0.781; 1.369, per 100 ng/shift) and ePM10 (OR = 1.029, 95%-CI = 0.879; 1.207, per 10 µg/m3). No decline in lung function was associated with PM10 exposure. However, forced expiratory volume during the first second and forced vital capacity lower than normal were positively associated with exposure duration (OR = 1.125, 95%-CI = 1.004; 1.260 and OR = 1.171, 95%-CI = 0.989; 1.386 per year, respectively). Current smoking was strongly associated with COPD prevalence (OR = 6.85, 95%-CI = 1.87; 25.10) and most lung function parameters. This is the first study assessing the relationship between long-term exposure to subway PM10 and respiratory health in subway workers. The risk estimates related with subway PM10 exposure are compatible with those related to outdoor PM10 exposure in the large recent studies. Large cohorts of subway workers are necessary to confirm these findings.

Occupational exposure to nanomaterials and biomarkers in exhaled air and urine: Insights from the NanoExplore international cohort.

The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1ß, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1ß and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study.