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.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroconversion and occupational exposure of employees at a Swiss university hospital: A large longitudinal cohort study.

BACKGROUND: The dynamics of coronavirus disease 2019 (COVID-19) seroconversion of hospital employees are understudied. We measured the proportion of seroconverted employees and evaluated risk factors for seroconversion during the first pandemic wave. METHODS: In this prospective cohort study, we recruited Geneva University Hospitals employees and sampled them 3 times, every 3 weeks from March 30 to June 12, 2020. We measured the proportion of seroconverted employees and determined prevalence ratios of risk factors for seroconversion using multivariate mixed-effects Poisson regression models. RESULTS: Overall, 3,421 participants (29% of all employees) were included, with 92% follow-up. The proportion of seroconverted employees increased from 4.4% (95% confidence interval [CI], 3.7%-5.1%) at baseline to 8.5% [(95% CI, 7.6%-9.5%) at the last visit. The proportions of seroconverted employees working in COVID-19 geriatrics and rehabilitation (G&R) wards (32.3%) and non-COVID-19 G&R wards (12.3%) were higher compared to office workers (4.9%) at the last visit. Only nursing assistants had a significantly higher risk of seroconversion compared to office workers (11.7% vs 4.9%; P = .006). Significant risk factors for seroconversion included the use of public transportation (adjusted prevalence ratio, 1.59; 95% CI, 1.25-2.03), known community exposure to severe acute respiratory coronavirus virus 2 (2.80; 95% CI, 2.22-3.54), working in a ward with a nosocomial COVID outbreak (2.93; 95% CI, 2.27-3.79), and working in a COVID-19 G&R ward (3.47; 95% CI, 2.45-4.91) or a non-COVID-19 G&R ward (1.96; 95% CI, 1.46-2.63). We observed an association between reported use of respirators and lower risk of seroconversion (0.73; 95% CI, 0.55-0.96). CONCLUSION: Additional preventive measures should be implemented to protect employees in G&R wards. Randomized trials on the protective effect of respirators are urgently needed.

Early Effect Markers and Exposure Determinants of Metalworking Fluids Among Metal Industry Workers: Protocol for a Field Study.

BACKGROUND: Exposure to aerosols from metalworking fluids (MWF) has previously been related to a series of adverse health outcomes (eg, cancer, respiratory diseases). Our present epidemiological study focuses on occupational exposures to MWF and a panel of exposure and effect biomarkers. We hypothesize that these health outcomes are caused by particle exposure that generates oxidative stress, leading to airway inflammation and ultimately to chronic respiratory diseases. We aimed to assess whether MWF exposure, in particular as characterized by its oxidative potential, is associated with biomarkers of oxidative stress and inflammation as well as genotoxic effects. OBJECTIVE: The ultimate goal is to develop exposure reduction strategies based on exposure determinants that best predict MWF-related health outcomes. The following relationships will be explored: (1) exposure determinants and measured exposure; (2) occupational exposure and preclinical and clinical effect markers; (3) exposure biomarkers and biomarkers of effect in both exhaled breath condensate and urine; and (4) biomarkers of effect, genotoxic effects and respiratory symptoms. METHODS: At least 90 workers from France and Switzerland (30 controls, 30 exposed to straight MWF and 30 to aqueous MWF) were followed over three consecutive days after a nonexposed period of at least two days. The exposure assessment is based on MWF, metal, aldehyde, and ultrafine particle number concentrations, as well as the intrinsic oxidative potential of aerosols. Furthermore, exposure biomarkers such as metals, metabolites of polycyclic aromatic hydrocarbons and nitrosamine are measured in exhaled breath condensate and urine. Oxidative stress biomarkers (malondialdehyde, 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, nitrates, and nitrites) and exhaled nitric oxide, an airway inflammation marker, are repeatedly measured in exhaled breath condensate and urine. Genotoxic effects are assessed using the buccal micronucleus cytome assay. The statistical analyses will include modelling exposure as a function of exposure determinants, modelling the evolution of the biomarkers of exposure and effect as a function of the measured exposure, and modelling respiratory symptoms and genotoxic effects as a function of the assessed long-term exposure. RESULTS: Data collection, which occurred from January 2018 until June 2019, included 20 companies. At the date of writing, the study included 100 subjects and 29 nonoccupationally exposed controls. CONCLUSIONS: This study is unique as it comprises human biological samples, questionnaires, and MWF exposure measurement. The biomarkers collected in our study are all noninvasive and are useful in monitoring MWF exposed workers. The aim is to develop preventative strategies based on exposure determinants related to health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13744.

Novel clinical scores for occupational asthma due to exposure to high-molecular-weight agents.

OBJECTIVE: Specific inhalation challenge (SIC) as the reference diagnostic test for occupational asthma (OA) is not widely available worldwide. We aimed to develop non-SIC-based models for OA. METHODS: Of 427 workers who were exposed to high-molecular-weight agents and referred to OA clinic at Montréal Sacré-Cœur Hospital between 1983 and 2016, we analysed 160 workers who completed non-specific bronchial hyper-responsiveness (NSBHR) tests and still worked 1 month before SIC. OA was defined as positive SIC. Logistic regression models were developed. The accuracy of the models was quantified using calibration and discrimination measures. Their internal validity was evaluated with bootstrapping procedures. The final models were translated into clinical scores and stratified into probability groups. RESULTS: The final model, which included age ≤40 years, rhinoconjunctivitis, inhaled corticosteroid use, agent type, NSBHR, and work-specific sensitisation had a reasonable internal validity. The area under the receiver operating characteristics curve (AUC) was 0.91 (95% CI 0.86 to 0.95), statistically significantly higher than the combination of positive NSBHR and work-specific sensitisation (AUC=0.84). The top 70% of the clinical scores (ie, the high probability group) showed a significantly higher sensitivity (96.4%vs86.9%) and negative predictive value (93.6%vs84.1%) than the combination of positive NSBHR and work-specific sensitisation (p value <0.001). CONCLUSIONS: We developed novel scores for OA induced by high-molecular-weight agents with excellent discrimination. It could be helpful for secondary-care physicians who have access to pulmonary function test and allergy testing in identifying subjects at a high risk of having OA and in deciding on appropriate referral to a tertiary centre.

Exhaled breath condensate as a matrix for combustion-based nanoparticle exposure and health effect evaluation.

BACKGROUND: Health assessment and medical surveillance of workers exposed to combustion nanoparticles are challenging. The aim was to evaluate the feasibility of using exhaled breath condensate (EBC) from healthy volunteers for (1) assessing the lung deposited dose of combustion nanoparticles and (2) determining the resulting oxidative stress by measuring hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA). METHODS: Fifteen healthy nonsmoker volunteers were exposed to three different levels of sidestream cigarette smoke under controlled conditions. EBC was repeatedly collected before, during, and 1 and 2 hr after exposure. Exposure variables were measured by direct reading instruments and by active sampling. The different EBC samples were analyzed for particle number concentration (light-scattering-based method) and for selected compounds considered oxidative stress markers. RESULTS: Subjects were exposed to an average airborne concentration up to 4.3×10(5) particles/cm(3) (average geometric size ∼60-80 nm). Up to 10×10(8) particles/mL could be measured in the collected EBC with a broad size distribution (50(th) percentile ∼160 nm), but these biological concentrations were not related to the exposure level of cigarette smoke particles. Although H(2)O(2) and MDA concentrations in EBC increased during exposure, only H2O2 showed a transient normalization 1 hr after exposure and increased afterward. In contrast, MDA levels stayed elevated during the 2 hr post exposure. CONCLUSIONS: The use of diffusion light scattering for particle counting proved to be sufficiently sensitive to detect objects in EBC, but lacked the specificity for carbonaceous tobacco smoke particles. Our results suggest two phases of oxidation markers in EBC: first, the initial deposition of particles and gases in the lung lining liquid, and later the start of oxidative stress with associated cell membrane damage. Future studies should extend the follow-up time and should remove gases or particles from the air to allow differentiation between the different sources of H(2)O(2) and MDA.

Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an emerging endoscopic technique for the diagnosis of peripheral lung lesions. A thorough analysis of ENB's yield and safety is required for comparison to other sampling modalities. OBJECTIVES: To describe ENB's yield and safety profile. METHODS: The MEDLINE and EMBASE databases were systematically searched for studies reporting ENB's yield for peripheral lung lesions. Two independent investigators extracted data and rated each study on a scale of methodological quality. Clearly defined performance outcomes were reconstructed and meta-analyzed. Subgroup analysis and meta-regression were used to identify possible sources of study heterogeneity. RESULTS: A total of 15 trials were included (1,033 lung nodules). A positive and definitive diagnosis was obtained after 64.9% of all ENB procedures (95% CI 59.2-70.3). Overall diagnostic accuracy was 73.9% (95% CI 68.0-79.2). Sensitivity to detect cancer was 71.1% (95% CI 64.6-76.8), with a negative predictive value of 52.1% (95% CI 43.5-60.6). Pneumothorax occurred in 3.1% of patients, requiring chest tube drainage in 1.6% of these cases. Original trials identified 6 variables associated with higher ENB yields: nodule location in the upper or middle lobes, nodule size, lower registration error, presence of a bronchus sign on CT imaging, combined use of an ultrasonic radial probe, and catheter suctioning as a sampling technique. Heterogeneity exploration revealed that studies using general anesthesia or rapid on-site cytological evaluation reported better yields. CONCLUSIONS: ENB is effective and particularly safe. Prospective studies are needed to clarify the role of several variables conditioning the yield of this technique.