The impact of occupational exposure to crystalline silica dust on respiratory function (airway obstruction and FEF25-75) in the French general population.

INTRODUCTION: Although several studies have studied the relationship between occupational exposure to crystalline silica dust and respiratory mortality, few have examined the relationship with impairments in respiratory function and the exposure threshold triggering spirometric monitoring in exposed workers. The objective of the present study was to evaluate the impact of exposure to crystalline silica dust on respiratory function. METHODS: We included 1428 male participants (aged 40 to 65) recruited from the French general population, at random from electoral rolls, in the cross-sectional ELISABET study and for whom data on forced expiratory flow-volume curve indices z-scores (calculated using the Global Lung Function Initiative 2012 equations) and exposure (via a questionnaire) were available. A cumulative exposure index (CEI) for crystalline silica dust (CEIsilica, expressed in mg.m-3.year) was calculated using the Matgéné occupational exposure matrix. RESULTS: 293 of the 1428 participants (20.52%) reported exposure to silica dust. We found that the adjusted z-scores for the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio decreased significantly as CEIsilica increased. After adjustment, the adjusted z-scores for FEV1/FVC (ß: -0.426 (95% confidence interval (CI): -0.792, -0.060) per 1 mg m-3.year increment) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) (ß: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEIsilica ≥1 mg m-3.year than in non-exposed participants. The likelihoods of having airway obstruction (odds ratio (OR): 3.056 (95% CI: 1.107, 7.626)) or having an impaired FEF25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEIsilica ≥1 mg m-3.year. CONCLUSION: Our results emphasize the importance of spirometry-based monitoring in workers exposed to more than 1 mg m-3.year of crystalline silica dust, in order to identify small airway obstruction or airway obstruction as early as possible.

Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality.

BACKGROUND AND OBJECTIVE: The definition of pre-capillary pulmonary hypertension (PH) has been modified, with lowering of the mean pulmonary arterial pressure (mPAP) threshold from 25 to 20 mmHg and addition of a mandatory criterion of pulmonary vascular resistance (PVR) ≥ 2 Wood units (WU). Our objectives were: 1/ to estimate the proportion of patients reclassified as having pre-capillary PH when using the new 2022 ESC/ERS hemodynamic criteria (i.e. mPAP 21-24 mmHg and PVR ≥ 2 WU), and to describe their clinical characteristics and outcome; and 2/ to study the relationship between PVR and survival in patients with mPAP > 20 mmHg. METHODS: We retrospectively analyzed consecutive SSc patients included in our National Reference Center for a first right-heart catheterization between 2003 and 2018. The association between survival and PVR was studied using smoothing splines. RESULTS: We included 126 SSc patients with mPAP > 20 mmHg. Among them, 16 (13%) had a baseline mPAP value between 21 and 24 mmHg and PVR ≥ 2 mmHg and were reclassified as pre-capillary PH; 10 of which (62%) raised their mPAP ≥ 25 mmHg during follow-up. In patients with mPAP > 20 mmHg, we observed a linear relation between PVR and mortality for values < 6 WU. CONCLUSION: A significant proportion of SSc patients is reclassified as having pre-capillary PH with the new 2022 ESC/ERS hemodynamic definition. Lowering the PVR threshold from 3 to 2 WU captures patients at risk of raising their mPAP > 25 mmHg, with a possibly less severe disease.

Residential exposure to outdoor air pollution and adult lung function, with focus on small airway obstruction.

Although a growing body of evidence suggests that chronic exposure to outdoor air pollution is linked to a decline in lung function, data on flow at low lung volumes that may be more specific of small airway obstruction are still scarce. We aimed to study the associations between residential exposure to air pollution and lung function, with specific focus on small airways obstruction. We assessed 2995 French participants (aged between 40 and 65) in the ELISABET cross-sectional survey. Residential exposures to nitrogen dioxide (NO2), particulate matter with a diameter <10 µm (PM10) and sulphur dioxide (SO2) were assessed. The spirometric parameters were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) and at 75% of FVC (FEF75). Coefficients in linear regression models were expressed as the z-score [95% confidence interval] for an increment of 5 µg/m3 in NO2 and 2 µg/m3 in PM10 and SO2. NO2 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.05]), FVC (-0.06 [-0.11;-0.02]), FEV1/FVC (-0.07 [-0.11;-0.03]), FEF25-75 (-0.09 [-0.14;-0.05]) and FEF75 (-0.08 [-0.12;-0.04]). PM10 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.04]), FVC (-0.06 [-0.11;-0.01]), FEV1/FVC (-0.06 [‒0.11;-0.01]), FEF25-75 (-0.08 [-0.13;-0.03]) and FEF75 (-0.08 [-0.12;-0.04]). SO2 was associated with significantly lower values of FEV1 (-0.09 [-0.16;-0.02]), FEV1/FVC (-0.07 [-0.13;-0.01]), FEF25-75 (-0.09 [-0.15;-0.02]) and FEF75 (-0.08 [-0.14;-0.03]) but not FVC (-0.05 [-0.11; 0.009]). Even though spatial variations in pollutant levels were low, residential exposure to outdoor air pollution was associated with lower lung function, including lower FEF25-75 and FEF75 suggesting small airway obstruction.

Exposure to metal fumes and circulating miRNAs in Algerian welders.

PURPOSE: A cross-sectional study was conducted in a group of Algerian welders to study the relationship between the exposure to metal particles from welding fumes and the concentration of three circulating miRNAs, miR-21, miR-146a and miR-155, as markers of renal function injury. METHODS: Characteristics of the subjects and the curriculum laboris were determined by questionnaires. We measured the concentrations of metals in blood and urine samples using ICP-MS. The three circulating miRNAs studied were measured by quantitative PCR. Associations between miRNAs and internal exposure markers were assessed by simple and multiple regression analyses. RESULTS: miR-21 was significantly lower among welders (p = 0.017), compared with controls, adjusted for age, body mass index, smoking status and seniority. Significant adjusted associations were observed between miR-21 or miR-155 and urinary chromium (p = 0.005 or p = 0.041, respectively), miR-146a and urinary nickel (p = 0.019). The results of the multivariate analysis showed that duration of employment was the main factor responsible for the variation of miRNAs among welders. CONCLUSION: In conclusion, a recent exposure to certain metals, mainly chromium and nickel, appears to be associated to a decrease in plasma expression of miR-21, miR-146a and miR-155. Further larger studies would help to determine the mechanisms of action of metal particles on miRNA expression.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. FINDINGS: In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21. INTERPRETATION: Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery. FUNDING: Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.

Sources of household air pollution: The association with lung function and respiratory symptoms in middle-aged adult.

INTRODUCTION: The objective of the present study was to investigate the relationship between sources of household air pollution, respiratory symptoms and lung function. METHODS: 3039 adults aged from 40 to 65 participated in the 2011-2013 ELISABET cross-sectional survey in northern France. Lung function was measured using spirometry. During a structured interview, respiratory symptoms, household fuels, exposure to moulds, and use of ventilation were recorded on a questionnaire. RESULTS: The self-reported presence of mould in at least two rooms (not including the bathroom and the kitchen) was associated with a 2.5% lower predicted forced expiratory volume in 1 s (95% confidence interval, -4.7 to -0.29; p-trend <0.05) and a higher risk of wheezing (p-trend < 0.001). Visible condensation was associated with wheezing (p < .05) and chronic cough (p < .05). There were no significant associations with the type of household fuel or inadequate ventilation/aeration. Similar results were found when the analyses were restricted to participants without known respiratory disease. CONCLUSION: Our results suggest that the presence of mould (known to be associated with more severe asthma symptoms) could also have an impact on respiratory symptoms and lung function in the general population and in populations without known respiratory disease.

Utility of measuring FEV0.75/FVC ratio in preschoolers with uncontrolled wheezing disorder.

Uncontrolled wheezing disorder is common in preschoolers and disease control assessment is challenging as parents frequently overestimate the extent to which their child's disease is controlled. This is the first study of forced expiratory volume in t s (FEVt)/forced vital capacity (FVC) ratio measurements (i.e. FEV1/FVC, FEV0.75/FVC and FEV0.5/FVC) in wheezy preschoolers in relation to disease control. Our objective was to evaluate whether FEVt/FVC ratios less than the lower limit of normal (LLN; z-score <-1.64) were associated with uncontrolled wheezing disorder in preschoolers.Valid FVC, FEV1, FEV0.75 and FEV0.5 values were obtained in 92 healthy and 125 wheezy (62% uncontrolled) children (3-5 years). Associations between spirometry value

Predictive value of exhaled nitric oxide and aerobic capacity for sepsis complications after liver transplantation.

Our objective was to investigate the predictive value of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) and aerobic capacity (peak VO2 ) for postoperative sepsis in liver transplantation candidates. Patients were identified and charts of all consecutive patients were prospectively reviewed. Bacterial sepsis represented the commonest postoperative complications (30%), which was attributed to peritonitis, pneumonia, and catheter-related infections. Preoperative FeNO and peak VO2 values were lower in patients with postoperative sepsis. Patients with sepsis required higher needs for mechanical ventilation and ICU length of stay. Inverse correlation was found between logarithmically FeNO-transformed data and systolic pulmonary artery pressure (r = -0.348; P = 0.018). Multivariate analyses using bootstrap sampling method indicated that odds of sepsis were associated with lower values of peak exercise VO2 [OR = 0.790 (0.592; 0.925)] and reduced log(FeNo) [OR = 0.027 (0.001; 0.451)], but not with higher MELD scores [OR = 1.141 (0.970; 1.486)]. By evaluating the cutoff for the ROC curves in each bootstrap resampling, median and 95% confidence interval were calculated for peak VO2 : 17 [16.2; 22] ml/kg/min and FeNO: 17.2 [13.0; 33.9] ppb. We conclude that low peak exercise VO2 and reduced FeNO may help identify patients who are at risk to develop perioperative sepsis.

Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients.

BACKGROUND: Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. METHODS AND RESULTS: Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A1C, but neither body mass index nor the insulin resistance index (homeostasis model assessment-insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A1C. CONCLUSION: Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in "metabolically healthy" obese patients at early stage in insulin resistance.

Increased Levels of 8-Isoprostane in EBC of NO2-Exposed Rats.

Several epidemiological studies have shown the impact on respiratory health of pollution of nitrogen dioxide (NO2), particulate matter (PM10), and ozone (O3) as an environmental mixture. However, the influence of individual components of airborne pollutants is less well known. Our study examined the cumulative effects of a single pollutant, NO2, on sensitized rats by measurement of isoprostane release in exhaled breath condensate (EBC). Three groups of six rats were used: (1) controls (only exposed to air), (2) sensitized and challenged by ovalbumin and exposed to air, and (3) sensitized, challenged by ovalbumin, and exposed to NO(2). There was no marked change in 8-isoprostane levels in EBC of sensitized rats, whereas a significant increase of 8-isoprostane was found in rats sensitized and exposed to NO2. Data indicate effect of exposure to NO2 is evident as increased 8-isoprostane levels in EBC, a relevant marker for assessment of pulmonary inflammation or oxidant stress and conventionally found in EBC of asthmatic subjects.

Occupational exposure to crystalline silica in a sample of the French general population.

OBJECTIVE: To describe the proportions of subjects exposed to crystalline silica and the sectors of activity concerned between 1965 and 2010 in a sample of the general French population. METHODS: We included 2942 participants aged 40 to 65 years, recruited at random from electoral rolls, from the French general population in the cross-sectional ELISABET study between 2011 and 2013. The proportions of subjects exposed to crystalline silica and their sectors of activity were determined on the basis of their career history and the use of the Matgéné job-exposure matrix. RESULTS: In the total sample, occupational exposure to crystalline silica was found for 291 subjects (9.9%) between 1965 and 2010, with a predominance of men (20.2% of exposed subjects among men (282 out of 1394) versus 0.6% among women (9 out of 1548)). The highest proportion of participants exposed to crystalline silica was reached in 1980 with 6.1% and then decreases to 4.4% in 2010. Among men, the most frequently exposed sectors of activity were manufacture of basic metals (41.5% of exposed men (117 out of 282)), specialised construction activities (23.1% of exposed men (65 out of 282)) and construction of buildings (14.2% of exposed men (40 out of 282)). CONCLUSIONS: Although the proportion of workers exposed to crystalline silica has been decreasing since the 1980s, it is still significant at least until 2010, particularly in the construction sector, and further research is needed to improve the monitoring of workers who are or have been exposed to crystalline silica.

Sniff nasal inspiratory pressure in the longitudinal assessment of young Duchenne muscular dystrophy children.

Traditional measures of respiratory function in children with Duchenne muscular dystrophy (DMD) are based on maximal inspiratory pressure (PImax) and vital capacity (VC). Sniff nasal inspiratory pressure (SNIP) measurements are easily performed by young children with neuromuscular disorders. The clinical value of SNIP in the longitudinal assessment of respiratory weakness remains to be assessed. The objective of the present study was to assess longitudinally the changes in SNIP, PImax and VC with age in DMD children. We hypothesised that their longitudinal assessment would show an earlier decline in SNIP than VC. A 3-year, prospective follow-up, at 6-month intervals of, 33 steroid-naïve, 5-20-year-old DMD patients was analysed using a linear mixed model. SNIP measurements were reliable (within-session coefficient of variation 8%). SNIP and VC increased until 10.5 and 12.5 years of age, respectively, and declined thereafter, while PImax did not change with age. SNIP was an earlier marker of decline in respiratory muscle strength (at 10.5 years) than VC (at 12.5 years) in young DMD patients. SNIP longitudinal assessment is useful in the detection of inspiratory strength decline in young DMD patients when VC values remain within normal values and as an outcome measure in clinical trials for emerging therapeutics in young DMD patients from the age of 5 years.

Assessment of lung hyperinflation in occupational chronic obstructive pulmonary disease: a multicentric cross-sectional study.

Occupational exposure is associated with elevated morbidity and lower quality of life in patients with chronic obstructive pulmonary disease (COPD). Static hyperinflation is an independent risk factor for all-cause mortality in COPD and for COPD exacerbation. In a multicentre, cross-sectional study (BPROFETIO), we sought to analyse the relationship between static hyperinflation and occupational exposure in patients with COPD with or without occupational exposure. MATERIAL AND METHODS: An overall 'whole working life' cumulative exposure index was calculated for occupational patients with COPD. Spirometry indices and lung volumes were measured according to the 2005 American Thoracic Society/European Respiratory Society guidelines. RESULTS: After adjustment for age, sex, height, body mass index, smoking and coexposure, the analysis for each occupational hazard showed a higher risk for hyperinflation and FEV1 decline or progression of COPD or GOLD stage for patients with COPD exposed to non-metallic inorganic dusts. CONCLUSION: Occupational exposures should be more investigated in clinical practice and studies as they contribute to the COPD heterogeneity and are associated for some with the development of a static hyperinflation; a condition that is known to have a negative impact on quality of life and survival.

Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.

BACKGROUND: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype. OBJECTIVES: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery. METHODS: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes. RESULTS: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64+CD14+CD16- circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. CONCLUSIONS: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).

AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice.

BACKGROUND: Acute ozone exposure causes lung oxidative stress and inflammation leading to lung injury. At least one mechanism underlying the lung toxicity of ozone involves excessive production of reactive oxygen and nitrogen intermediates such as peroxynitrite. In addition and beyond its major prooxidant properties, peroxynitrite may nitrate tyrosine residues altering phosphorylation of many protein kinases involved in cell signalling. It was recently proposed that peroxynitrite activates 5'-AMP-activated kinase (AMPK), which regulates metabolic pathways and the response to cell stress. AMPK activation as a consequence of ozone exposure has not been previously evaluated. First, we tested whether acute ozone exposure in mice would impair alveolar fluid clearance, increase lung tissue peroxynitrite production and activate AMPK. Second, we tested whether loss of AMP-activated protein kinase alpha1 subunit in mouse would prevent enhanced oxidative stress and lung injury induced by ozone exposure. METHODS: Control and AMPKα1 deficient mice were exposed to ozone at a concentration of 2.0 ppm for 3 h in glass cages. Evaluation was performed 24 h after ozone exposure. Alveolar fluid clearance (AFC) was evaluated using fluorescein isothiocyanate tagged albumin. Differential cell counts, total protein levels, cytokine concentrations, myeloperoxidase activity and markers of oxidative stress, i.e. malondialdehyde and peroxynitrite, were determined in bronchoalveolar lavage (BAL) and lung homogenates (LH). Levels of AMPK-Thr172 phosphorylation and basolateral membrane Na(+)-K(+)-ATPase abundance were determined by Western blot. RESULTS: In control mice, ozone exposure induced lung inflammation as evidence by increased leukocyte count, protein concentration in BAL and myeloperoxidase activity, pro-inflammatory cytokine levels in LH. Increases in peroxynitrite levels (3 vs 4.4 nM, p = 0.02) and malondialdehyde concentrations (110 vs 230 µmole/g wet tissue) were detected in LH obtained from ozone-exposed control mice. Ozone exposure consistently increased phosphorylated AMPK-Thr172 to total AMPK ratio by 80% in control mice. Ozone exposure causes increases in AFC and basolateral membrane Na(+)-K(+)-ATPase abundance in control mice which did not occur in AMPKα1 deficient mice. CONCLUSIONS: Our results collectively suggest that AMPK activation participates in ozone-induced increases in AFC, inflammation and oxidative stress. Further studies are needed to understand how the AMPK pathway may provide a novel approach for the prevention of ozone-induced lung injury.

Assessing the applicability of the new Global Lung Function Initiative reference values for the diffusing capacity of the lung for carbon monoxide in a large population set.

BACKGROUND: The single-breath diffusing capacity of the lung for carbon monoxide (DLCO) interpretation needs the comparison of measured values to reference values. In 2017, the Global Lung Function Initiative published new reference values (GLI-2017) for DLCO, alveolar volume (VA) and transfer coefficient of the lung for carbon monoxide (KCO). We aimed to assess the applicability of GLI-2017 reference values for DLCO on a large population by comparing them to the European Community of Steel and Coal equations of 1993 (ECSC-93) widely used. METHODS: In this retrospective study, spirometric indices, total lung capacity, DLCO, VA and KCO were measured in adults classified in 5 groups (controls, asthma, chronic bronchitis, cystic fibrosis, and interstitial lung diseases (ILD)). Statistical analysis comparing the 2 equations sets were stratified by sex. RESULTS: 4180 tests were included. GLI-2017 z-scores of the 3 DLCO indices of the controls (n = 150) are nearer to 0 (expected value in a normal population) than ECSC-93 z-scores. All groups combined, in both genders, DLCO GLI-2017 z-scores and %predicted are significantly higher than ECSC z-scores and %predicted. In the ILD group, differences between the 2 equation sets depend on the DLCO impairment severity: GLI-2017 z-scores are higher than ECSC z-scores in patients with no or "mild" decrease in DLCO, but are lower in "moderate" or "severe" decrease. CONCLUSION: GLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases.

Reproducibility of reading echocardiographic parameters to assess severity of mitral regurgitation. Insights from a French multicentre study.

BACKGROUND: Poor reproducibility in assessment of mitral regurgitation (MR) has been reported. AIM: To investigate the robustness of echocardiographic MR assessment in 2019, based on improvements in technology and the skill of echocardiographists regarding MR quantification. METHODS: Reproducibility in parameters of MR severity and global rating were tested using transthoracic echocardiography in 25 consecutive patients independently analysed by 16 junior and senior cardiologists specialized in echocardiography (400 analyses per parameter). RESULTS: Overall interobserver agreement for mechanism definition, effective regurgitant orifice area (EROA) and regurgitant volume (RVol) was moderate, and was lower in secondary MR. Interobserver agreement was substantial for EROA [0.61, 95% confidence interval (CI) 0.45-0.75] and moderate for RVol with the PISA method (0.50, 95% CI 0.33-0.56) in senior physicians and was fair in junior physicians (0.33, 95% CI 0.19-0.51 and 0.36, 95% CI 0.36-0.43, respectively). Using a multiparametric approach, overall interobserver agreement for grading MR severity was fair (0.30), was slightly better in senior than in junior physicians (0.31 vs. 0.28, respectively) with substantial or almost perfect agreement more frequently observed in senior versus junior physicians (52% vs. 36%, respectively). CONCLUSION: Reproducible transthoracic echocardiography MR quantification remains challenging in 2019, despite the expected high skills of echocardiographers regarding MR at the time of dedicated percutaneous intervention. The multiparametric approach does not entirely alleviate the substantial dispersion in measurement of MR severity parameters, whereas reader experience seems to partially address the issue. Our study emphasizes the continuing need for multimodality imaging and education in the evaluation of MR among cardiologists.

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.