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Sébastien Hulo,1 Jocelyn Inamo,2 Aurélie Dehon,3 Olivier Le Rouzic,4 Jean-Louis Edme,1 Remi Neviere51Université Lille, CHU Lille, EA 4483, IMPact de l’Environnement Chimique sur la Santé humaine, Lille, France; 2Département de Cardiologie – CHU Fort de France, Martinique – Faculté de Médecine – Université des Antilles, France; 3Pôle d’Anesthésie Réanimation ADRU, CHU Nîmes, Nîmes, France; 4Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; 5Université Lille, Inserm, CHU Lille, Lille Inflammation Research International Center, Lille, FrancePurpose: Metabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients.Patients and methods: We prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake (V’O2) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (ICdyn)) with percentage of maximal HR and CMI.Results: Aerobic capacity (median interquartile ranges) peak V’O2, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL·kg-1·min-1 and CMI worsened according to GOLD severity. The optimal knot of ICdyn was equal to −0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6). Conclusion: COPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.Keywords: COPD, hyperinflation, chronotropic incompetence, exercise

Background: Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short-term inflammation-mediated outcomes after cardiac surgery. The impact of CH on long-term postoperative outcomes remains unknown., Methods and Results: In this cohort study, patients undergoing elective cardiac surgery were included from January 2017 to September 2019. Patients were screened for CH using a predefined gene panel of 19 genes. Recorded clinical events were all-cause death, major adverse cardiac and cerebral events including cardiovascular death, myocardial infarction or nonscheduled coronary revascularization, stroke, and hospitalization for acute heart failure. The primary study outcome was time to a composite criterion including all-cause mortality and major adverse cardiac and cerebral events. Among 314 genotyped patients (median age: 67 years; interquartile range 59-74 years), 139 (44%) presented with CH, based on a variant allelic frequency ≥1%. Carriers of CH had a higher proportion of patients with a history of atrial fibrillation (26% for CH versus 17% for non-CH carriers, P =0.022). The most frequently mutated genes were DNMT3A , TET2 , and ASXL1 . After a median follow-up of 1203 [813-1435] days, the primary outcome occurred in 50 patients. After multivariable adjustment, CH was independently associated with a higher risk for the primary outcome (hazard ratio, 1.88 [95% CI, 1.05-3.41], P =0.035). Most adverse events occurred in patients carrying TET2 variants., Conclusions: In patients undergoing cardiac surgery, CH is frequent and associated with a 2-fold increased long-term risk for major adverse clinical outcomes. CH is a novel risk factor for long-term postcardiac surgery complications and might be useful to personalize management decisions., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03376165.

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., (© 2024. The Author(s).)

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)., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from Fédération Française de Cardiologie, Fondation Leducq convention 16CVD01 (“Defining and Targeting Epigenetic Pathways in Monocytes and Macrophages That Contribute to Cardiovascular Disease”), the European Genomic Institute for Diabetes (ANR-10-LABX-0046), Fondation Pour la Recherche Médicale (REFERENCE PROJET EQU202203014650), and Agence Nationale de la Recherche (TOMIS leukocytes: ANR-CE14-0003-01). Dr Staels is a recipient of an Advanced European Research Council Grant (694717). Dr Vicario was supported by the 2018 American Association for Cancer Research–Bristol Myers Squibb Fellowship for Young Investigators in Translational Immuno-Oncology. Work at the Memorial Sloan Kettering Cancer Center (MSKCC) is supported by an MSKCC core grant (P30 CA008748), National Institutes of Health grants 1R01NS115715-01, 1 R01 HL138090-01, and 1 R01 AI130345-01, Basic and Translational Immunology Grants from the Ludwig Center for Cancer Immunotherapy to Dr Geissmann. Dr de Winther is funded by grants from the Netherlands Heart Foundation (CVON: GENIUS2) and the Netherlands Heart Foundation and Spark-Holding (2019B016). Dr Neele is a Dekker fellow of the Netherlands Heart Foundation (2020T029). Dr White is founder and owner of Resphera Biosciences. Dr Geissmann has performed consulting for Third Rock Ventures. Dr Fragkogianni is employed by Tempus Labs. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 (CEI silica , 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 (FEV 1 /FVC) ratio decreased significantly as CEI silica increased. After adjustment, the adjusted z-scores for FEV 1 /FVC (β: -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 (FEF 25-75 ) (β: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEI silica ≥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 FEF 25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEI silica ≥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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

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.

Background: A relevant morning-afternoon variation in ischemia-reperfusion (IR) insult after cardiac surgery has been demonstrated. We speculated that the biorhythm might also impact systemic reactions involved in acute kidney injury (AKI) following cardiac surgery. We aimed at investigating incidence, determinants and prognostic impact of AKI in a large cohort of patients referred for surgical aortic valve replacement (SAVR) according to surgery time-of-day., Methods: Between 2009 and 2015, we explored consecutive patients referred to our Heart Valve Center (CHU Lille) for first SAVR. Patients undergoing morning and afternoon SAVR were matched into pairs by propensity score and followed for major events (ME) i.e. cardiovascular death, cardiac hospitalization for acute heart failure (HF) and post-operative myocardial infarction. AKI was defined using KDIGO classification., Results: In the matched population (n = 596 patients), AKI occurred in 20% of patients. After multivariable adjustment, medical history of hypertension, pre-operative renal function impairment and cardio-pulmonary bypass duration were independent predictors of AKI onset. Post-operative AKI was significantly associated with increased occurrence of ME and specifically of cardiac hospitalization for HF (p = 0.0035 and p = 0.0071, respectively) during the 500 days following SAVR. Finally, AKI occurrence and severity were similar between morning and afternoon groups (p = 0.98 and p = 0.99, respectively)., Conclusion: We showed that despite current high-quality patient management during and following SAVR, peri-operative AKI remains frequent, developing in 20% of patients, and clearly worsens mid-term post-operative outcomes. AKI more often develops in patients with pre-operative chronic kidney disease and long duration of cardiac surgery but is not influenced by surgery time-of-day., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background & Aims: Increased nitric oxide is involved in abnormal hemodynamic parameters and respiratory function of cirrhotic patients. We aimed to quantify partitioning exhaled nitric oxide measurements in exhaled air in liver transplantation (LT) candidates and evaluate their relationships with chronotropic incompetence and aerobic capacity., Methods: We compared exhaled nitric oxide (NO) measurements, heart rate response and peak oxygen uptake during incremental exercise in liver transplantation candidates to those of controls., Results: As opposed to healthy control subjects, LT candidates displayed elevated alveolar NO, blunted chronotropic response and reduced V'O 2 at maximal exercise. In LT candidates, median peak V'O 2 was 18.7 ml kg -1 min -1 (interquartile range (IQR) 16.2; 21.8), corresponding to 65% (IQR 57; 72) of the predicted value. Compared with controls, LT candidates had increased levels of alveolar NO (median (IQR) 2.0 (1.2; 2.2) versus 3.1 (2.3; 4.5), p < 0.001). In controls, no relations were found between alveolar NO and V'O 2 peak or heart rate reserve whereas in cirrhotic patients, negative correlations and negative slopes were found between alveolar NO and V'O 2 peak and heart rate reserve decrease., Conclusions: Increasing alveolar NO could be a specific pathophysiological condition limiting aerobic capacity in LT candidates.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Our objective was to investigate the predictive value of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) and aerobic capacity (peak VO 2 ) 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 VO 2 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 VO 2 [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 VO 2 : 17 [16.2; 22] ml/kg/min and FeNO: 17.2 [13.0; 33.9] ppb. We conclude that low peak exercise VO 2 and reduced FeNO may help identify patients who are at risk to develop perioperative sepsis., (© 2016 Steunstichting ESOT.)

Objective: Low beryllium exposure can induce pulmonary granulomatosis, so called berylliosis. For occupational health monitoring, it is more relevant to assess the internal dose of Be received by the lungs than urinary or atmospheric Be. Exhaled breath condensate (EBC) is a matrix collected non-invasively that derives from the airway lining fluid. EBC beryllium (Be) levels were evaluated as a marker of occupational exposure in a primary aluminum production plant., Methods: We collected urine and EBC from controls and workers recently exposed to beryllium in the pot room and the anode repair sectors, and calculated a cumulative beryllium exposure index (CBEI) summing the number of years of employment in each task and multiplying by the estimated average beryllium exposure for the task. Concentrations of beryllium and aluminum were measured in EBC (Be-EBC and Al-EBC) and in urine (Be-U and Al-U) by ICP-MS., Results and Conclusion: We have shown that it was possible to measure Be and Al in workers' EBC. Compared with controls and after adjustment for smoking status, levels of Be-EBC and Al-EBC were higher in pot room workers and exposed subjects, respectively. Due to its relationship with CBEI, but not with Be-U, it appears that Be-EBC could be a promising marker of occupational exposure and provide additional toxicokinetic information in occupational health studies., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

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.

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., (© 2014 American Heart Association, Inc.)

Objective: To evaluate manganese in exhaled breath condensate (Mn-EBC) as an indicator of exposure to fumes from metal inert gas welding process., Methods: We collected EBC and urine from 17 welders and 16 unexposed control subjects after 5 days exposure. Concentrations of manganese (Mn), nickel (Ni), iron (Fe) and chromium (Cr) were measured in EBC and urine samples and correlated with cumulative exposure indices for the working week (CIW) and for the total welding years (WY), based on duration of welding activity and atmospheric metal measurements., Results: Concentrations of Mn and Ni in EBC were significantly higher among welders than controls whereas this difference was not significant for Mn in urine. Levels of Mn and Ni in EBC were not correlated with their respective levels in urine. The linear regressions found significant positive coefficients between Mn-EBC, Ni-EBC, Ni-U and Cr-U concentrations and the cumulative exposure indices. Taking into account tobacco use, statistical analysis showed the same trends except for the relationship between Mn-U and CIW., Conclusion: This pilot study showed that Mn-EBC, as well as Ni-EBC, can serve as reliable indices of occupational exposure to welding fumes and provide complimentary toxicokinetic information to that provided by urine analyses., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Our aim was to determine preoperative aerobic capacity (oxygen uptake [V'O2 ]) and prevalence of exercise oscillatory ventilation (EOV), underlying clinical characteristics of patients with EOV, and significance of reduced aerobic capacity and EOV in predicting mortality after liver transplantation. We prospectively studied 263 patients who underwent elective liver transplantation. Patients were followed up for 1 year. Despite minor impairment of resting cardiopulmonary function, preoperative aerobic capacity was reduced (peak V'O2 : 64 ± 19% predicted). EOV occurred in 10% of patients. Model for End-Stage Liver Disease score tended to be higher in patients with EOV compared to patients without, but failed to reach significance (p = 0.09). EOV patients had lower peak V'O2 and higher ventilatory drive. EOV was more frequent in nonsurvivors than in survivors (30% vs. 9%, p = 0.01) and was independently associated with posttransplant all-cause 1-year mortality. Reduced peak V'O2 best predicted the primary composite endpoint defined as 1-year mortality and/or prolonged hospitalization and early in-hospital mortality. Multivariate analysis revealed EOV (χ(2), 3.96; p = 0.04) and V'O2 (χ(2), 4.28; p = 0.04) as independent predictors of mortality and so-called primary composite endpoint, respectively. EOV and reduced peak V'O2 may identify high-risk candidates for liver transplantation, which would motivate a more aggressive treatment when detected., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: We present pulmonary disorders of four employees who were exposed to high concentration of pure mica dust in a muscovite milling unit., Method: All cases underwent traditional examinations with a dual-energy chest computed tomographic scan. An analysis of exhaled breath condensate by Raman microspectrometry and of mineralogical content of a lung biopsy was performed for one case., Results: All cases showed bilateral micronodular ground glass opacities and mediastinal and hilar hyperdense lymph nodes consistent with the nodal sequestration of mineral particles. Histological analysis showed giant cell granulomas without typical silicotic nodule with high concentration of birefringent particles consistent with mica. Mica particles found in the exhaled breath condensate were identical to particles in ambient air at the company., Conclusion: Occupational exposure to mica dust is responsible for diffuse infiltrative lung disease by overload processes.

The analysis of exhaled breath condensate (EBC) offers the potential for identifying lung disease markers in humans and animals, but methodological issues and standardised procedures need to be addressed before the technique can be considered for use in applications to help understand the role of environmental pollution in respiratory diseases. The purpose of this study was to develop and implement a new device using a glass-chamber for collecting EBC non-invasively from rats in order to analyse EBC markers in lipopolysaccharide (LPS)-induced acute lung injury. Eighty-four adult rats were used in five different series of experiments to determine the source of EBC formation, intra-day and inter-day variability, and the influence of environmental parameters on EBC markers. The hypothesis that inflammation induces an oxidative stress was assessed by measuring pH, nitrogen oxides (NOx) and hydrogen peroxide (H(2)O(2)) in EBC. The results confirmed that EBC fluid was generated at the level of the respiratory tract. The repeatability studies of disease markers indicated higher concentrations of NOx and H(2)O(2) at midday compared to the morning, but there were no significant difference between measurements on consecutive days. EBC volume was influenced by both ambient temperature and humidity. Moreover, 3h after LPS challenge, significantly increased concentrations of both NOx and H(2)O(2) were observed in EBC of the LPS group compared with controls (P=0.005 and P=0.027, respectively). These results suggested that EBC collection may be a valuable tool to monitor the presence of markers, such as NOx and H(2)O(2), in an animal model of LPS-induced acute lung injury., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

New methods for exploring pulmonary inflammation might be useful: measurements of exhaled nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) in exhaled breath condensate (EBC). The authors describe the application and utility of these methods in a case report of pediatric nurse presenting an occupational asthma to latex. Despite compliance with avoidance measures, respiratory discomfort had worsened during work. Classical tests (spirometry, monitoring of peak expiratory flow) were not contributing to objectify the discomfort. Exhaled NO and H(2)O(2) in EBC increased immediately after work periods, compared with rest periods. Application of these new methods, at the same time, in workplace appears useful in the objective demonstration of a temporal relation between work and respiratory problems. The results allowed the occupational physician to transfer the patient to a new work station more appropriate for her respiratory health status.

Objective: Severe pectus excavatum are common in adult patients, often causing psychological complaints and physiological impairments. Although lung function at rest may minimally deteriorate after surgical correction, it remains unclear if surgery improves exercise capacity. The objective of present study is to assess whether the surgical repair of pectus excavatum in adults would improve exercise tolerance., Methods: A prospective study was performed to compare pulmonary and cardiovascular function at rest and at maximal exercise, before, and at 1 year after pectus excavatum repair., Results: From December 2005 to May 2009, 120 adult patients underwent pectus excavatum repair. Of these patients, 70 (nine women, 61 men) underwent thorough preoperative, 6-, and 12-month postoperative assessments, and were included in the present study. Age ranged from 18 to 62 years (mean 27 years). The pectus index (Haller index) was 4.5 ± 1.1. Lung function tests at rest were within the normal range, whereas maximal oxygen uptake (peak VO₂) was only 77 ± 2% of the predicted value. At 1-year follow-up, the pectus excavatum repair was associated with minor changes in lung function tests and significant increase (p=0.0005) in VO₂ (87 ± 2% of the predicted value). Postoperative O₂ pulse increase at maximal exercise suggested that aerobic capacity improvement was the result of better cardiovascular adaptation at maximal workload., Conclusion: These results demonstrate sustained improvement in exercise cardiopulmonary function at 1-year follow-up of pectus excavatum surgical repair in adult patients., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate thin-section computed tomography (CT) in depicting longitudinal changes in the lung parenchyma., Materials and Methods: One hundred eleven volunteers underwent sequential examination with thin-section CT and pulmonary function tests over a mean period of 5.5 years. According to their smoking habits between initial evaluation (T0) and follow-up (T1), the subjects were classified as persistent current smokers (n = 57), persistent nonsmokers (n = 31), persistent ex-smokers (n = 13), or quitters (n = 10)., Results: Significant differences in CT findings between T0 and T1 were seen in only the group of persistent current smokers, who showed a higher frequency of emphysema (40% vs 26%; P =.005) and ground-glass attenuation (42% vs 28%; P =.02). Individual analysis of follow-up CT scans in the 19 persistent current smokers with micronodules at T0 demonstrated (a) no changes in seven cases, (b) a higher profusion of micronodules in seven cases, and (c) replacement of micronodules with emphysema in five cases. Subjects with emphysema and/or areas of ground-glass attenuation at T0 had a significantly more rapid decline in lung function than did those with a normal CT scan., Conclusion: Emphysema and/or ground-glass attenuation are linked with impairment of ventilatory lung function over time in persistent current smokers.

A back school was established in 1992 at the University Hospital of Lille (France) for employees with low back pain. We report its medical and socioeconomic benefits with a mean time to follow-up of 4 years. Our retrospective study included 108 health care workers and provides objective data (absenteeism, use of health care) and subjective information (progression of pain and disorder, social and professional impact) before training and a mean of 4 years after training. We found that 92% of the participants were satisfied with the training and that back pain had regressed or resolved for 55% of them. Both the frequency and duration of pain had decreased significantly. Seventy percent continue to apply the advice they received in their everyday life. Dealing with the problems specific to professional activities contributed to reduce the strain experienced on the job by the health care workers and improved their satisfaction at work. Global absenteeism was reduced by 57.8%, whereas it was reduced by 33% for back pain alone 4 years after implementing this program. Our study provides evidence of the positive impact of this type of training on the way back pain is perceived and on everyday life. The assessment of the cost/efficiency ratio completes the list of durable benefits reported here.

Purpose: To evaluate the frequency and morphologic characteristics of air trapping in volunteers with various smoking habits., Materials and Methods: Two hundred fifty volunteers (133 women, 117 men; mean age, 39 years), including 144 smokers, 47 ex-smokers, and 59 nonsmokers, prospectively underwent inspiratory and expiratory high-spatial-resolution computed tomography (CT) and pulmonary function tests (PFTs). The frequency and characteristics of air trapping were evaluated according to the population's smoking habits and PFT results., Results: The overall frequency of air trapping was 62% (155 of 250 subjects). Lobular air trapping was depicted in 117 (47%) of 250 subjects, without significant differences among smokers (n = 91), ex-smokers (n = 33), and nonsmokers (n = 31) (P =.118). Segmental and lobar air trapping (38 [15%] of 250) were more frequent among smokers (24 [26%] of 91) and ex-smokers (nine [27%] of 33) (P <.001). No relationship was found between air trapping and functional indexes of small-airway disease when the CT pattern of air trapping was considered. The strongest relationship between CT abnormalities and functional alterations at the small-airways level was between inspiratory CT features of bronchiolitis: ground-glass opacity, ill-defined micronodules, bronchiolectasis, and air flow at low lung volumes., Conclusion: Whereas a significant relationship was observed between segmental and lobar air trapping and cigarette consumption, lobular air trapping was not found to reflect functional impairment at the small-airways level.

The prevalence of cytomegalovirus (CMV) infection varies not only from one country to another, but also with social, economic, and environmental conditions and with professional activity. Health care workers in contact with the main vectors of the CMV (i.e., children and immunosuppressed patients) are particularly exposed to the infection. We assessed the prevalence of the virus among health care personnel in light of CMV epidemiology and the recent shift in living conditions and family size. Our study was included in a broader program evaluating the risk of infection among female hospital workers of childbearing age. The goal of the program was to implement appropriate preventive measures for personnel who were not immune to the infection. Consequently, we included only female caregivers who worked with children or immunosuppressed patients. The study was based on a clinical examination, a medical and occupational questionnaire, the assessment of tasks performed; and CMV serologic testing. The overall seroprevalence was 44.25% in our population (n = 400) and was comparable regardless of the place of work. Prevalence differed significantly with age and parity, and we also found that it was higher among personnel who worked in closer contact with the patients (nurse's aides, pediatric nurse's aides) than among those whose tasks required more technical skills (nurses, pediatric nurses) (57.3% vs 34.5%, P < 0.01). The logistic regression analysis between prevalence of CMV antibodies, age, parity, and type of job showed that "contact job" was as significant a factor as parity to explain immunization in our population (odds ratio, 2.2). We also determined a correlation between the prevalence of CMV antibodies and tasks performed. In addition, we found a non-negligible group of non-immune personnel (55.75%) and young workers (mean age: 33.4) who were potentially exposed to infection. This points to the need to establish a prevention program.

Over the past few years, many studies, including one on our previous work, have examined the chronic effects of fumes from stainless steel (SS) welding on the health of welders. These chronic effects have been related to concentrations of chromium and nickel in SS welding fumes. The present study examined the acute respiratory effects of welding fumes in the workplace by measuring the across-shift changes in a population of 144 SS and mild steel (MS) welders and 223 controls. Manual Metal Arc, Metal Inert Gas, and Tungsten Inert Gas welding processes were studied. Pulmonary function tests were performed at the start (ante, or A) and at the end (post, or P) of the work shift. The study of sensitization to harmful respiratory effects of welding was based on the study of the (P-A)/A ratio (%) of the spirometric variations during the shift. The means of these ratios in the control subjects were used to account for the circadian effect. In SS welders we observed a significant decrease in forced vital capacity (FVC) during the shift. Significant across-shift decrements in forced expiratory volume in 1 second (FEV1) and FVC were related to the SS welding exposure compared with MS welding. Moreover, the across-shift decreases in FEV1, FVC, and peak expiratory flow (PEF) were significantly related to the Manual Metal Arc welding process, compared with Metal Inert Gas techniques (respectively, PEF = -2.7% of baseline values [SD, 11.9] vs 2.0% of baseline values [SD, 7.7] P = 0.04; FVC = -1.5% of baseline values [SD, 4.8] vs 0.2% of baseline values [SD, 4.5] P = 0.05). We also demonstrated the influence of duration of SS welding exposure on the course of lung function during the work shift. After 20 years of SS welding activity, SS welders had more significant across-shift decreases than MS welders with a similar MS exposure duration (respectively, FEV1 = -2.7% of baseline values [SD, 5.9] vs 0.7% of baseline values [SD, 4.2] P = 0.008; PEF = -3.8% of baseline values [SD, 9.6] vs 2.3% of baseline values [SD, 6.5] P = 0.04). We concluded that welding-related lung function responses are seen in SS compared with MS welders and in those with a longer lifetime welding history.

In the last few years, many studies have been carried out concerning the effects of fumes from stainless steel (SS) welding on the health of welders. The respiratory effects of exposure to SS welding fumes have already been studied, but the results of lung function investigations have not been consistent. However, the main factor of risk for the welders' health seems to be related to the great concentration of chromium and nickel contained in fumes coming from SS welding. The aim of this study was to detect the chronic effects of SS welding exposure on pulmonary symptoms and ventilatory function tests. Respiratory symptoms and lung function tests were studied in 134 SS welders and 252 controls (C). Welders and controls were of similar average age, height, and duration in employment. The smoking habits of the groups were also similar. The medical questionnaire on respiratory symptoms was a version of the Medical Research Council questionnaire, modified by the British Occupational Hygiene Society. The flow-volume curves were performed with a calibrated pneumotachograph spirometer before each subject started working. After adjustment for tobacco habits, the SS welders presented a higher prevalence of bronchial irritative symptoms such as cough (P = 0.01) or sputum production (P = 0.02) than the controls. On the other hand, chronic bronchitis appeared to be significantly linked to tobacco consumption. The pulmonary function analysis underscored no significant difference between stainless steel welders and controls (forced expiratory volume in one second, observed/predicted: SS = 0.99 vs C = 0.98; maximal midexpiratory flow, observed/predicted: SS = 0.90 vs C = 0.92; maximal expiratory flow at 50 % of the forced vital capacity, observed/predicted: SS = 0.95 vs C = 0.95). On the other hand, by the mean of the two-ways analysis, a significant tobacco effect was found, without exposure or interaction of tobacco-exposure effects. There was no influence of the specific welding processes on the spirographic parameters, but a decrease in spirographic values after 25 years of welding activity was evident. The results of multiple regression indicated that age was not a confounding factor.

The purpose of this study was to assess the accuracy of transverse CT scans as well as multiplanar (MPR) and three-dimensional (3D) reconstructions in the evaluation of obstructive lesions of the central airways. A total of 64 patients were evaluated for the presence of obstructive lesions of the central tracheobronchial tree with transverse spiral CT scans, multiplanar reformations (MPRs), 3D shaded surface displays (3D SSDs) and minimum intensity projections (MIPs). The findings of these modalities were then compared with those obtained at bronchoscopy. The severity, length, and shape of airway narrowing were analyzed comparatively on the four sets of images. Transverse CT scans and MPRs had a similar accuracy (99%) in detecting obstructive airway lesions. The accuracy of both was significantly higher than that of 3DSSDs (90%, p < 0.05) and MIPs (81%; p < 0.01). There was no statistically significant difference between the four imaging modalities in the analysis of the morphology of airway stenoses. Symmetric stenoses were similarly analyzed on the four sets of images, whereas MPRs and MIPs failed to depict accurately simple and complex asymmetric stenoses. Transverse CT scans are accurate in the depiction of obstructive lesions of the central airways and may be complemented by MPRs and/or 3DSSDs in their morphologic evaluation.

To determine the histopathologic basis for computed tomographic (CT) interpretation of smokers' lung and the accuracy of CT in the detection of alterations related to cigarette smoking, parenchymal lung lesions were studied from 41 heavy smokers who underwent thoracotomy for removal of a solitary pulmonary nodule. CT scanning of the resected lungs, corresponding exactly to the sections seen on preoperative CT scans, resulted in the following pathologic-CT correlations. Areas of ground-glass attenuation seen on preoperative CT scans (n = 11 [27%]) were related to three main histologic features: (a) accumulation of pigmented macrophages and mucus in the alveolar spaces, associated with mild interstitial inflammation and/or fibrosis (n = 7); (b) thickening of the alveolar walls with inflammatory cells with normal alveolar spaces (n = 3); and (c) presence of organizing alveolitis (n = 1). Parenchymal micronodules depicted presurgically (n = 4 [10%]) corresponded to bronchiolectases with peribronchiolar fibrosis (n = 4) associated with obliterative bronchiolitis in one patient. When emphysema was detected presurgically (n = 21 [51%]), it was always present at pathologic study to a higher extent than initially suspected.

A prospective computed tomographic (CT) study was performed to determine the prevalence of lung changes in smokers. The study group comprised 175 healthy adult volunteers (current smokers, n = 98; ex-smokers, n = 26; nonsmokers, n = 51). The subjects underwent clinical examination, pulmonary function tests, chest radiography, and conventional and high-resolution CT (HRCT). Significant differences between current smokers, ex-smokers, and nonsmokers were observed with HRCT in the identification of subpleural (P = .11) and parenchymal (P < .001) micronodules, emphysema (P < .001), and areas of ground-glass attenuation (P = .0001). All subjects had normal pulmonary function. Parenchymal micronodules, areas of ground-glass attenuation, and emphysema were observed with a significant predominance in the upper lung zones (P < .01). Presence of emphysema and abnormal bronchial wall thickening were the only HRCT signs associated with significantly lower values of functional parameters. These data support the concept that parenchymal abnormalities can be detected in healthy smokers with normal findings at chest radiography and pulmonary function tests.