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.

Air Pollution and Primary DNA Damage among Zagreb (Croatia) Residents: A Cross-Sectional Study.

More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM10 exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure.

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.

Job Exposure Matrix, a Solution for Retrospective Assessment of Particle Exposure in a Subway Network and Their Long-Term Effects.

INTRODUCTION: Health effects after long-term exposure to subway particulate matter (PM) remain unknown due to the lack of individual PM exposure data. This study aimed to apply the job exposure matrix (JEM) approach to retrospectively assess occupational exposure to PM in the Parisian subway. METHODS: Job, the line and sector of the transport network, as well as calendar period were four JEM dimensions. For each combination of these dimensions, we generated statistical models to estimate the annual average PM10 concentration using data from an exhaustive inventory of the PM measurement campaigns conducted between 2004 and 2020 in the Parisian subway and historical data from the Parisian air pollution monitoring network. The resulting JEM and its exposure estimates were critically examined by experts using the uncertainty analysis framework. RESULTS: The resulting JEM allows for the assignment of the estimated annual PM10 concentration to three types of professionals working in the subway: locomotive operators, station agents, and security guards. The estimates' precision and validity depend on the amount and quality of PM10 measurement data used in the job-, line-, and sector-specific models. Models using large amounts of personal exposure measurement data produced rather robust exposure estimates compared to models with lacunary data (i.e., in security guards). The analysis of uncertainty around the exposure estimates allows for the identification of the sources of uncertainty and parameters to be addressed in the future in order to refine and/or improve the JEM. CONCLUSIONS: The JEM approach seems relevant for the retrospective exposure assessment of subway workers. When applied to available data on PM10, it allows for the estimation of this exposure in locomotive operators and station agents with an acceptable validity. Conversely, for security guards, the current estimates have insufficient validity to recommend their use in an epidemiological study. Therefore, the current JEM should be considered as a valid prototype, which shall be further improved using more robust measurements for some jobs. This JEM can also be further refined by considering additional exposure determinants.

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.

Predictive factors of return-to-work trajectory after work-related rotator cuff syndrome: A prospective study of 96 workers.

OBJECTIVE: Sustained return to work after surgery for work-related rotator cuff syndrome (WRRCS) remains quite difficult. The main purpose of the present study was to identify predictive factors of a return-to-work (RTW) trajectory. METHODS: A total of 96 workers with WRRCS were identified by 4 surgeons. They were followed prospectively before and after the surgery, until 1 year after RTW, or for 20 months after surgery when they did not. Participants completed a series of standardized questionnaires related to working conditions, health, and beliefs, and performed functional tests at the inclusion time. During the follow-up period, they were regularly asked about their working conditions (present or not at work), activity (normal or lightened physical duties) and schedules (full- or part-time job). Statistical analysis was based on single- and multiple-factor models of prediction of the workers' trajectory. RESULTS: Three trajectories of RTW were distinguished, considering RTW and absenteeism that occurred during the follow-up: stable, unstable, and non-RTW. The median age of the sample was 49.5 [45.0-54.0], with 67.7% of workers employed in highly physically demanding jobs. In the multiple factor model, three factors were highly predictive of the trajectory: perceived health before surgery, having had a repaired ruptured-rotator-cuff tendinopathy, and the level of physical demand of the job. CONCLUSION: Three easy-to-collect predictive factors of RTW trajectory have been identified. They may be useful for healthcare professionals and care givers to identify vulnerable workers' risk of occupational dropout after arthroscopic surgery for rotator cuff tendinopathy.

Clinical Use of an Exposure, Symptom, and Spirometry Algorithm to Stratify Smokers into COPD Risk Phenotypes: A Case Finding Study Combined with Smoking Cessation Counseling.

Background: Chronic obstructive pulmonary disease (COPD) case-finding aims to detect airflow obstruction in symptomatic smokers and ex-smokers. We used a clinical algorithm including smoking, symptoms, and spirometry to classify smokers into COPD risk phenotypes. In addition, we evaluated the acceptability and effectiveness of including smoking cessation advice in the case-finding intervention. Methods: Smoking, symptoms, and spirometry abnormalities (airflow obstruction: forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] <0.7 or preserved-ratio spirometry (FEV1<80% of predicted value and FEV1/FVC ratio ≥ 0.7)] were assessed in a group of 864 smokers aged ≥ 30 years. The combination of these parameters allowed the identification of 4 phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms; normal spirometry; possible COPD), Phenotype C (no symptoms; abnormal spirometry; possible COPD), and Phenotype D (symptoms; abnormal spirometry; probable COPD). We assessed phenotype differences in clinical variables and modeled the trend from phenotype A to phenotype D. Smoking cessation advice based on spirometry was provided. Follow-up was done by telephone 3 months later. Results: Using smokers without symptoms or abnormal spirometry (phenotype A; n=212 [24.5%]) as a reference, smokers were classified into possible COPD (phenotype B;n=332 [38.4%]; and C: n=81 [9.4%]) and probable COPD (phenotype D: n=239 [27.2%]). The trend from baseline phenotype A to probable COPD phenotype D was significant for the number of cigarettes/day and the number of years of smoking (p=0.0001). At follow-up, 58 (7.7%) of the respondents (n=749) reported that they had quit smoking. Conclusions: Our clinical algorithm allowed us to classify smokers into COPD phenotypes whose manifestations were associated with smoking intensity and to significantly increase the number of smokers screened for COPD. Smoking cessation advice was well accepted, resulting in a low but clinically significant quit rate.

Hematological variations in healthy participants exposed 2 h to propylene glycol ethers under controlled conditions.

Glycol ethers are solvents used in a plethora of occupational and household products exposing the users to potential toxic effects. Several glycol ethers derived from ethylene glycol induce hematological toxicity, such as anemia in workers. The exposure effects on blood cells of glycol ethers derived from propylene glycol are unknown in humans. The aim of our study was to evaluate blood parameters indicative of red blood cell (RBC) hemolysis and oxidative stress in participants exposed to propylene glycol (propylene glycol monobutyl ether (PGBE) and propylene glycol monomethyl ether (PGME)), two extensively used propylene glycol derivatives worldwide. Seventeen participants were exposed 2 h in a control inhalation exposure chamber to low PGME (35 ppm) and PGBE (15 ppm) air concentrations. Blood was regularly collected before, during (15, 30, 60, and 120 min), and 60 min after exposure for RBC and oxidative stress analyses. Urine was also collected for clinical effects related to hemolysis. Under the study conditions, our results showed that the blood parameters such as RBCs, hemoglobin concentration, and white blood cells tended to increase in response to PGME and PGBE exposures. These results raise questions about the possible effects in people regularly exposed to higher concentrations, such as workers.

A harmonized protocol for an international multicenter prospective study of nanotechnology workers: the NanoExplore cohort.

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers' ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers' health by updating the follow-up of the cohort. New hypothesis could be also considered.

Pleural Plaques and the Role of Exposure to Mineral Particles in the Asbestos Post-exposure Survey.

BACKGROUND: Previous studies have inconsistently reported associations between refractory ceramic fibers (RCFs) or mineral wool fibers (MWFs) and the presence of pleural plaques. All these studies were based on chest radiographs, known to be associated with a poor sensitivity for the diagnosis of pleural plaques. RESEARCH QUESTION: Does the risk of pleural plaques increase with cumulative exposure to RCFs, MWFs, and silica? If the risk does increase, do these dose-response relationships depend on the co-exposure to asbestos or, conversely, are the dose-response relationships for asbestos modified by co-exposure to RCFs, MWFs, and silica? STUDY DESIGN AND METHODS: Volunteer workers were invited to participate in a CT scan screening program for asbestos-related diseases in France. Asbestos exposure was assessed by industrial hygienists, and exposure to RCFs, MWFs, and silica was determined by using job-exposure matrices. A cumulative exposure index (CEI) was then calculated for each subject and separately for each of the four mineral particle exposures. All available CT scans were submitted to randomized double reading by a panel of radiologists. RESULTS: In this cohort of 5,457 subjects, significant dose-response relationships were determined after adjustment for asbestos exposure between CEI to RCF or MWF and the risk of PPs (ORs of 1.29 [95% CI, 1.00-1.67] and 1.84 [95% CI, 1.49-2.27] for the highest CEI quartile, respectively). Significant interactions were found between asbestos on one hand and MWF or RCF on the other. INTERPRETATION: This study suggests the existence of a significant association between exposure to RCFs and MWFs and the presence of pleural plaques in a large population previously exposed to asbestos and screened by using CT scans.

Consultation frequency and general practitioners' and practices' characteristics.

BACKGROUND: High workloads generated by a few patients who consult very frequently can become huge burdens for general practitioners (GPs). Patient-related factors have been repeatedly associated with frequent consultations, but there is evidence that GPs can also influence that frequency. We investigated how patients, GPs and their practices' organisational characteristics were associated with consultation frequency. METHODS: Data came from the SPAM Prev (Swiss Primary Health Care Active Monitoring, Prevention in primary care) national, cross-sectional survey conducted in 2015-16, including 167 GPs and 1105 patients. GPs completed an online questionnaire focused on practice organisation. Patients randomly recruited in general practices completed a questionnaire with fieldworkers. Factors predicting consultation frequency were investigated using multilevel Poisson regression models. RESULTS: Negative associations with consultation frequency were found for females (Incidence Rate Ratio (IRR) 0.94, 95%CI [0.88-1.01]), less compliant patients (IRR 0.91, 95%CI [0.84-0.98]), high self-perceived health status (IRR 0.8, 95%CI [0.75-0.84]) and physical exercise (IRR 0.87, 95%CI [0.81-0.94]). Consultation frequencies were higher among patients with sleeping problems (IRR 1.08, 95%CI [0.96-1.23]), psychological distress (IRR 1.66, 95%CI [1.49-1.86]), chronic diseases (IRR 1.27, 95%CI [1.18-1.37]) and treatment with medication (IRR 1.24, 95%CI [1.12-1.37]). Positive associations with consultation frequency were found among GPs working longer hours (IRR 1.21, 95%CI [1.01-1.46]). Using shared medical records (IRR 0.79, 95%CI [0.67-0.92]) were negatively associated with consultation frequency. CONCLUSION: GPs' practices' characteristics, like patients', are predictive of patients' consultation frequency, but those associations' underlying mechanisms require further qualitative investigation. These new findings could help optimise intervention strategies and reduce healthcare costs.

Effect of Periodic Voluntary Interventions on Trapezius Activation and Fatigue During Light Upper Limb Activity.

OBJECTIVE: The effects of diverse periodic interventions on trapezius muscle fatigue and activity during a full day of computer work were investigated. BACKGROUND: Musculoskeletal disorders, including trapezius myalgia, may be associated with repeated exposure to prolonged low-level activity, even during light upper-extremity tasks including computer work. METHODS: Thirty healthy adults participated in a study that simulated two 6-hour workdays of computer work. One workday involved imposed periodic passive and active interventions aimed at disrupting trapezius contraction monotony (Intervention day), whereas the other workday did not (Control day). Trapezius muscle activity was quantified by the 3-dimensional acceleration of the jolt movement of the acromion produced by electrically induced muscle twitches. The spatio-temporal distribution of trapezius activity was measured through high-density surface electromyography (HD-EMG). RESULTS: The twitch acceleration magnitude in one direction was significantly different across measurement periods (p = 0.0156) on Control day, whereas no significant differences in any direction were observed (p > 0.05) on Intervention day. The HD-EMG from Intervention day showed that only significant voluntary muscle contractions (swing arms, Jacobson maneuver) induced a decrease in the muscle activation time and an increase in the spatial muscle activation areas (p < 0.01). CONCLUSION: Disruption of trapezius monotonous activity via brief voluntary contractions effectively modified the ensuing contraction pattern (twitch acceleration along one axis, active epochs reduction, and larger spatial distribution). The observed changes support an associated reduction of muscle fatigue. APPLICATION: This study suggests that disruptive intervention activity is efficient in reducing the impact of trapezius muscle fatigue.

Prevalence and Persistence of Symptoms in Adult COVID-19 Survivors 3 and 18 Months after Discharge from Hospital or Corona Hotels.

COVID-19 is characterized by persistent symptoms beyond acute illness. In this prospective cohort study of patients with COVID-19, we sought to characterize the prevalence and persistence of symptoms up to 18 months after diagnosis. We followed 166 patients and assessed their symptoms during acute illness, and at 3 and 18 months after disease onset. The mean number of symptoms per patient during acute disease was 2.3 (SD:1.2), dropping to 1.8 (SD:1.1) at 3 months after recovery and to 0.6 (SD:0.9) at 18 months after recovery. However, this decrease was not unidirectional. Between acute illness and 3 months, the frequency of symptoms decreased for cough (64.5%→24.7%), ageusia (21.7% to6%), anosmia (17.5%→5.4%), and generalized pain (10.8% to 5.4%) but increased for dyspnea (53%→57.2%) weakness (47%→54.8%), and brain fog (3%→8.4%). Between 3 and 18 months, the frequency of symptoms decreased for all symptoms but remained relatively high for dyspnea (15.8%), weakness (21.2%), and brain fog (7.3%). Symptoms may persist for at least 18 months after acute COVID-19 infection. During the medium- to long-term recovery period, the prevalence of some symptoms may decrease or remain stable, and the prevalence of others may increase before slowly decreasing thereafter. These data should be considered when planning post-acute care for these patients.

Co-exposures to physical and psychosocial work factors increase the occurrence of workplace injuries among French care workers.

Objective: The aim of this study was to analyze the effect of co-exposures to physical and psychosocial factors (PSF) regarding the incidence of workplace injuries (WI) among care workers. Additional objective was to identify the work factors associated with the co-exposure combinations leading to the highest rates of WI. Methods: The study sample consisted of 4,418 care workers participating to the French Working Conditions Survey both in 2013 and 2016. WI were assessed during the 4-year follow-up by matching the databases of the National Health Insurance Funds' compensation system. We assessed exposure for physical factors and PSF using factorial analyses and hierarchical clustering. We implemented a Poisson regression model with the WI incidence as the outcome and the clusters as independent variables of interest. Logistic regression model allowed identifying the work factors that predicted co-exposure combinations with a WI rate > 40%. Results: WI were highly related to both physical and psychosocial exposures. With low exposure to one or the other, there was no increased risk of WI. Physical factors and PSF potentiated each other and their co-exposure significantly increased the risk of WI, with model predicted rates per 1,000 persons-year for those most exposed to physical risk of 14.6 [4.5-24.8] with low PSF and 38.0 [29.8-46.3] with high PSF. Work factors that predicted co-exposure combinations with a rate > 40 WI% were: working as nursing assistant or hospital services officer, lack of predictability and flexibility of schedules, overtime, controlled schedules, work-family imbalance and insufficient preventive measures. Conclusions: Our findings highlight the need to take into account psychosocial factors in addition of only considering physical factors when analyzing WI occurrence, as usually done. Prevention actions must be taken to reduce both physical and psychosocial exposure. These results provide keys points for the prevention of WI among care workers.

Identifying complex patients in family medicine for potential benefit from a case manager: a short questionnaire derived from the INTERMED Self-Assessment (IMSA) questionnaire.

PURPOSE: To investigate how useful the Intermed-Self Assessment (IMSA) questionnaire and its components were for identifying which patient candidates would benefit most from case management (CM) in general practice. METHODS: The study was carried out in a group family medicine practice in Lausanne comprising seven GPs and four medical assistants, from February to April 2019. All the patients attending the practice between February and April 2019 were invited to complete the IMSA questionnaire. Additionally, their GPs were asked for their opinions on the potential benefits of each patient being assigned a case manager. Each IMSA item's value has been assessed as a predictor of GPs' opinions by using multivariate logistic models. A score including items retained as predictor was built. RESULTS: Three hundred and thirty one patients participated in the study (participation rate: 62%). Three items from the 20 item IMSA were sufficient to predict GPs' opinions about whether their patients could be expected to benefit if assigned a case manager. Those items addressed the patient's existing chronic diseases (item1), quality of life in relation to existing diseases (item 3), and their social situation (item 9). Using these three items as a score, a cut-off at 4 gave a sensitivity of 70% (ability to correctly identify patients who could benefit from a CM) and specificity of 73% (ability to correctly identify patients who should not benefit from a CM) and concerned about one patient in two. CONCLUSION: Identifying complex patients suitable for case management remains a challenge for primary care professionals. This paper describes a novel approach using a structured process of combining the results of standardized tools such as the one defined in this study, and the experience of the primary care team.

Oxidative Potential in Exhaled Air (OPEA) as a Tool for Predicting Certain Respiratory Disorders in the General Adult Population: Cross-Sectional Analysis Nested in the Swiss Health Study.

In a pilot clinical study, OPEA allowed for distinguishing participants with and without chronic obstructive pulmonary disease. This study aimed to assess whether abnormal spirometry parameters and immunity against SARS-CoV-2 are associated with increased OPEA and estimating the OPEA reference interval. Swiss adult residents of the Vaud Canton aged 20-69 years randomly selected from the Federal Statistical Office's registries, speaking French or German, were included and examined between 1 October 2020 and 31 December 2021. General health status and presence of respiratory diseases were assessed by questionnaire and spirometry. Spirometric results were compared with the predicted values and their lower limits of norms of the Global Lung Function Initiative. SARS-CoV-2-seroprevalence was assessed using the Luminex-based test of IgG. Statistical analysis consisted of unilateral t-tests and ANOVA. Lower and upper limit of OPEA reference interval with associated 90%-confidence interval (90%CI) were estimated for the sub-sample of healthy adults by bootstrap, after excluding outliers. The study sample included 247 participants. SARS-CoV-2-seropositive participants and those with an obstructive syndrome had a significantly higher OPEA than seronegative and healthy participants. The estimated reference interval was: -0.0516 (90%CI = -0.0735; -0.0316); -0.0044 (90%CI = -0.0224; 0.0153). OPEA could predict inflammatory-based respiratory disorders, but needs further validation in different settings and for other pathologies.

Season, Vegetation Proximity and Building Age Shape the Indoor Fungal Communities' Composition at City-Scale.

Exposure to particular microbiome compositions in the built environment can affect human health and well-being. Identifying the drivers of these indoor microbial assemblages is key to controlling the microbiota of the built environment. In the present study, we used culture and metabarcoding of the fungal Internal Transcribed Spacer ribosomal RNA region to assess whether small-scale variation in the built environment influences the diversity, composition and structure of indoor air fungal communities between a heating and an unheated season. Passive dust collectors were used to collect airborne fungi from 259 dwellings representative of three major building periods and five building environments in one city-Lausanne (Vaud, Switzerland)-over a heating and an unheated period. A homogenous population (one or two people with an average age of 75 years) inhabited the households. Geographic information systems were used to assess detailed site characteristics (altitude, proximity to forest, fields and parks, proximity to the lake, and density of buildings and roads) for each building. Our analysis indicated that season was the factor that explained most of the variation in colonies forming unit (CFU) concentration and indoor mycobiome composition, followed by the period of building construction. Fungal assemblages were more diverse during the heating season than during the unheated season. Buildings with effective insulation had distinct mycobiome compositions from those built before 1975 - regardless of whether they were constructed with pre-1945 technology and materials or 1945 - 1974 ones. The urban landscape-as a whole-was a significant predictor of cultivable Penicillium load-the closer the building was to the lake, the higher the Penicillium load-but not of fungal community composition. Nevertheless, the relative abundance of eleven fungal taxa detected by metabarcoding decreased significantly with the urbanization gradient. When urban landscape descriptors were analyzed separately, the explanatory power of proximity to vegetation in shaping fungal assemblages become significant, indicating that land cover type had an influence on fungal community structure that was obscured by the effects of building age and sampling season. In conclusion, indoor mycobiomes are strongly modulated by season, and their assemblages are shaped by the effectiveness of building insulation, but are weakly influenced by the urban landscape.

Associations between urinary biomarkers of oxidative stress and biomarkers of tobacco smoke exposure in smokers.

Oxidative stress can contribute to the development of diseases, and may originate from exposures to toxicants commonly found in air pollution and cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Yet, associations between these exposures and oxidative stress biomarkers are poorly characterized. We report here novel associations between 14 exposure biomarkers of PAHs and VOCs, and two oxidative stress biomarkers; 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-isoprostaglandin F2α (8-isoprostane) in urine obtained from smokers participating in an ongoing clinical study (ESTxENDS, NCT03589989). We also assessed associations between six biomarkers of tobacco smoke exposure (metabolites of nicotine and tobacco-specific nitrosamines (TSNAs)) and both oxidative stress biomarkers. We then quantified the relative importance of each family of the 20 exposure biomarkers on oxidative stress. Participating smokers (153 men and 117 women, median age 44 years) had on average smoked 25 [2-62] years and smoked about 17 [5-40] cigarettes per day at the time of the study. Multiple linear regression results showed an association between 8-oxodG concentrations and the following metabolites in decreasing relative importance: PAHs (beta coefficient ß = 0.105, p-value <0.001, partial R2 = 0.15) > VOCs (ß = 0.028, p < 0.001, partial R2 = 0.09) > nicotine (ß = 0.226, p < 0.001, partial R2 = 0.08); and between 8-isoprostane concentrations and metabolites of PAHs (ß = 0.117, p < 0.001, partial R2 = 0.14) > VOCs (ß = 0.040, p < 0.001, partial R2 = 0.14) > TSNAs (ß = 0.202, p = 0.003, partial R2 = 0.09) > nicotine (ß = 0.266, p < 0.001, partial R2 = 0.08). Behavioral factors known to contribute to oxidative stress, including sleep quality, physical activity, and alcohol consumption, did not play a significant role. Exposures to PAHs and VOCs among smokers were significantly associated with oxidative stress.

Associating Air Pollution with Cytokinesis-Block Micronucleus Assay Parameters in Lymphocytes of the General Population in Zagreb (Croatia).

Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health.