Issue 3-The occupational burden of respiratory diseases, an update.

INTRODUCTION AND AIMS: Workplace exposures are widely known to cause specific occupational diseases such as silicosis and asbestosis, but they also can contribute substantially to causation of common respiratory diseases. In 2019, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) published a joint statement on the occupational burden of respiratory diseases. Our aim on this narrative review is to summarise the most recent evidence published after the ATS/ERS statement as well as to provide information on traditional occupational lung diseases that can be useful for clinicians and researchers. RESULTS: Newer publications confirm the findings of the ATS/ERS statement on the role of workplace exposure in contributing to the aetiology of the respiratory diseases considered in this review (asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, infectious pneumonia). Except for COPD, chronic bronchitis and infectious pneumonia, the number of publications in the last 5 years for the other diseases is limited. For traditional occupational lung diseases such as silicosis and asbestosis, there are old as well as novel sources of exposure and their burden continues to be relevant, especially in developing countries. CONCLUSIONS: Occupational exposure remains an important risk factor for airways and interstitial lung diseases, causing occupational lung diseases and contributing substantially in the aetiology of common respiratory diseases. This information is critical for public health professionals formulating effective preventive strategies but also for clinicians in patient care. Effective action requires shared knowledge among clinicians, researchers, public health professionals, and policy makers.

Switching from the transrectal to the transperineal route: A single center experience.

INTRODUCTION: This study aimed to evaluate the feasibility of switching from transrectal to transperineal prostate biopsy (TPPBx) by urologists with no previous experience with TPPBx. Material A monocentric clinical study with exhaustive and consecutive inclusions was conducted between January and November 2021, including 105 consecutive patients who underwent TPPBx performed by two senior urologists with no previous experience of TPPBx (GR, FB). Biopsies were performed under local anesthesia (LA) without antibioprophylaxis. The main objective was to assess the safety of this procedure. Adverse events were classified according to the Clavien-Dindo score. The secondary objectives were to assess the level of pain experienced during the different steps of the procedure using a numerating rating scale (NRS), the rate of clinically significant prostate cancer (csPCa) detected, and the level of anxiety using the Hospital Anxiety and Depression Scale (HAD). RESULTS: No major complications (Clavien-Dindo score≥3) were reported. One patient presented with acute urinary retention (1%) and a urinary tract infection (1%). Other adverse events were hematuria (43%), hemospermia (23%), rectal bleeding (1%), perineal hematoma (3%), persistent perineal pain (5%), and de novo erectile dysfunction (2%). The median level of pain on NRS for the procedure was 2.00 (IQ: 1.00-4.00); it was 3.00 (IQ: 2.00-5.00) during LA and 3.00 (IQ: 2.00-5.00) during punctions. In anxious patients (HAD score>10), the level of pain during the procedure was 2.5 (IQ: 2.00-3.00). Overall, csPCa was detected in 63%. CONCLUSION: TPPBx under LA without antibioprophylaxis provides few complications, an acceptable pain threshold, and a satisfactorily rate of csPCa detection, even if performed by urologists with no previous experience of TPPBx.

The position during urine sample collection from young precontinent children through a bag does not limit contamination rates: Results from a randomized controlled trial: Does infant position influence quality of urine collection?

AIM: Despite its limitation, bag collection is still widely used for a preliminary urine screening test in non-toilet-trained children suspected of febrile urinary tract infection. A previous study conducted by our group raised the hypothesis that the absence of direct contact between urine and the perinea during urine collection could limit urine contamination by perineal flora. The aim of this study was to evaluate the impact of the patient's position during urine collection (upright standing position versus free position) on the rate of contaminated urine samples in non-toilet-trained children with suspected febrile urinary tract infection. METHODS: This prospective, randomized, controlled study took place in seven pediatric emergency departments. Two groups were compared: the intervention group (infants held in an upright standing position during urination) and the control group (free position during urination). RESULTS: Among the 800 pediatric patients randomized to the study, 124 had a urine culture, 60 in the intervention group and 64 in the control group. Among the 124 urine cultures, 12 (9.7%) were contaminated: eight (13.3%) in the intervention group and four (6.3%) in the control group (p = 0.1824). CONCLUSION: The results show that the patient's position does not have a significant impact on the quality of urine samples collected by bag.

The fingerprint of the 2018 drought in Europe on ground-based atmospheric CO2 measurements.

During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.

Proteome changes in muscles, ganglia, and gills in Corbicula fluminea clams exposed to crude oil: Relationship with behavioural disturbances.

The use of online remote control for 24/7 behavioural monitoring can play a key role in estimating the environmental status of aquatic ecosystems. Recording the valve activity of bivalve molluscs is a relevant approach in this context. However, a clear understanding of the underlying disturbances associated with behaviour is a key step. In this work, we studied freshwater Asian clams after exposure to crude oil (measured concentration, 167 ± 28 µg·L-1) for three days in a semi-natural environment using outdoor artificial streams. Three complementary approaches to assess and explore disturbances were used: behaviour by high frequency non-invasive (HFNI) valvometry, tissue contamination with polycyclic aromatic hydrocarbons (PAH), and proteomic analysis. Two tissues were targeted: the pool adductor muscles - retractor pedal muscle - cerebral and visceral ganglia, which is the effector of any valve movement and the gills, which are on the frontline during contamination. The behavioural response was marked by an increase in valve closure-duration, a decrease in valve opening-amplitude and an increase in valve agitation index during opening periods. There was no significant PAH accumulation in the muscle plus nervous ganglia pool, contrary to the situation in the gills, although the latter remained in the low range of data available in literature. Major proteomic changes included (i) a slowdown in metabolic and/or cellular processes in muscles plus ganglia pool associated with minor toxicological effect and (ii) an increase of metabolic and/or cellular processes in gills associated with a greater toxicological effect. The nature of the proteomic changes is discussed in terms of unequal PAH distribution and allows to propose a set of explanatory mechanisms to associate behaviour to underlying physiological changes following oil exposure. First, the first tissues facing contaminated water are the inhalant siphon, the mantle edge and the gills. The routine nervous activity in the visceral ganglia should be modified by nervous information originating from these tissues. Second, the nervous activity in the visceral ganglia could be modified by its own specific contamination. Third, a decrease in nervous activity of the cerebral ganglia close to the mouth, including some kind of narcosis, could contribute to a decrease in visceral ganglia activity via a decrease or blockage of the downward neuromodulation by the cerebro-visceral connective. This whole set of events can explain the decrease of metabolic activity in the adductor muscles, contribute to initiate the catch mechanism and then deeply modify the valve behaviour.

Asiatic clam Corbicula fluminea exhibits distinguishable behavioural responses to crude oil under semi-natural multiple stress conditions.

Aquatic ecosystems are subject to many anthropogenic disturbances, and understanding their possible impacts is a real challenge. Developing approaches based on the behaviour of bivalve mollusks, an integrating marker of the state of the organisms, and therefore of their environment, is relevant, whether within a natural ecosystem or an ecosystem subject to industrial activities. The main objective of this study was to identify by HFNI Valvometry a reliable and reproducible clam behavioural response in the presence of crude oil in a multistress context. To closely replicate actual field conditions, Corbicula fluminea was exposed in outdoor artificial streams that were subject to natural variations and were continuously fed by fresh water from the Gave de Pau (S.W. France). After a period of 26 days in these artificial streams, the clams (n = 14-16 per condition) were separately exposed for 10 days to crude oil alone, crude oil and barium, crude oil and noise pollution, crude oil and turbidity pulses, barium alone, noise pollution alone, turbidity pulses alone or natural changes alone. The secondary objective was to characterize the accumulation of polycyclic aromatic hydrocarbons (PAH) in 3 tissues (gills, adductor muscles and foot) in clams exposed for 10 days to crude oil alone or under multistress conditions (n = 5 clams per condition) and then to compare the accumulation and behaviour of clams under these conditions. The response of clams to crude oil alone or under multistress conditions was visually and statistically significant and not confounded by the other disturbances tested, despite large variations in water temperature. In the presence of crude oil, the behaviour of clams was characterized by an increase in valve-closure duration, a decrease in valve-opening amplitude and an increase in valve agitation index. In the presence of crude oil, the clam behaviour showed no direct relationship with PAH accumulation in the gills, adductor muscles or foot, although hypothetical mechanisms are discussed. This work supports the growing interest in studying the behaviour of bivalve mollusks in the context of biomonitoring of the aquatic environment surrounding oil facilities.

Pulmonary toxicity associated with pomalidomide.

Pomalidomide, previously used to treat multiple myeloma, has been reported to cause acute pulmonary toxicity that improves with drug discontinuation. We present a case of delayed pneumonitis with persistent fibrosis associated with pomalidomide. A 61-year-old male treated with pomalidomide and corticosteroids presented with acute on chronic dyspnea, profound hypoxemia, and ground glass opacities on computerized tomographic imaging. Corticosteroid taper and discontinuation of pomalidomide resulted in clinical improvement, but with substantial residual pulmonary fibrosis. Given the temporal improvement, but not resolution, following discontinuation of an agent with an established propensity for lung injury, we attribute this presentation to pomalidomide toxicity.

Exposure to second-hand tobacco smoke and respiratory symptoms in non-smoking adults: cross-sectional data from the general population of Telemark, Norway.

BACKGROUND: In Norway, data on the association between second-hand tobacco smoke (SHS) exposure at home and respiratory symptoms in adults are limited. METHODS: We assessed the association between self-reported exposure to SHS and the prevalence of respiratory symptoms among never-smokers aged 16 to 50 years from the general population who were included in a cross-sectional population-based study in Telemark County, Norway. Logistic regression analysis was used to estimate the odds ratios of symptoms among 8850 never-smokers who provided an affirmative response to questions regarding SHS; 504 (5.7%) of these reported that they lived in a home with daily or occasional indoor smoking. RESULTS: Productive cough and nocturnal dyspnoea were statistically associated with daily SHS exposure (ORs 1.5 [95% CI 1.04-2.0] and 1.8 [1.2-2.7], respectively). In analyses stratified by gender, nocturnal dyspnoea was associated with SHS among women (OR 1.8 [1.1-3.1]), but not among men (OR 0.93 [0.49-1.8]). Symptoms were not associated with occasional SHS exposure in the entire group, but infrequent exposure among men only was associated with increased prevalence of chronic cough; (OR 1.6; [1.04-2.6]) and was negatively associated with wheeze; (OR 0.44 [0.21-0.92)]. CONCLUSIONS: Daily SHS exposure in private homes was associated with productive cough and nocturnal dyspnoea. Our results suggest that preventive measures may be needed to reduce the respiratory effects of SHS at home. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073708 Registered February 27. 2014.

Methylmercury complexes: Selection of thermodynamic properties and application to the modelling of a column experiment.

Complexation with methyl groups produces the most toxic form of mercury, especially because of its capacity to bioconcentrate in living tissues. Understanding and integrating methylation and demethylation processes is of the utmost interest in providing geochemical models relevant for environmental assessment. In a first step, we investigated methylation at equilibrium, by selecting the thermodynamic properties of different complexes that form in the chemical system Hg-SO3-S-Cl-C-H2O. The selection included temperature dependencies of the equilibrium constants when available. We also considered adsorption and desorption reactions of both methylated and non-methylated mercury onto mineral surfaces. Then we assessed the kinetics of methylation by comparing a dedicated column experiment with the results of a geochemical model, including testing different methylation and demethylation kinetic rate laws. The column system was a simple medium: silicic sand and iron hydroxides spiked with a mercury nitrate solution. The modelling of methylmercury production with two different rate laws from the literature is bracketing the experimental results. Dissolved mercury, iron and sulfate concentrations were also correctly reproduced. The internal evolution of the column was also correctly modeled, including the precipitation of mackinawite (FeS) and the evolution of dissolved iron. The results validate the conceptual model and underline the capacity of geochemical models to reproduce some processes driven by bacterial activity.

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study.

Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study from 2010 to 2016, we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-min walk test exercise capacity as predictors of HRQL change. Among 211 initial participants (92% of those eligible), LT improved HRQL by all 5 measures (p < 0.05) and all but SF12-Mental Health improved by threefold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p < 0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net benefits of LT.

Distribution of Water in Synthetic Calcium Silicate Hydrates.

Understanding calcium silicate hydrates (CSHs) is of paramount importance for understanding the behavior of cement materials because they control most of the properties of these man-made materials. The atomic scale water content and structure have a major influence on their properties, as is analogous with clay minerals, and we should assess these. Here, we used a multiple analytical approach to quantify water distribution in CSH samples and to determine the relative proportions of water sorbed on external and internal (interlayer) surfaces. Water vapor isotherms were used to explain the water distribution in the CSH microstructure. As with many layered compounds, CSHs have external and internal (interlayer) surfaces displaying multilayer adsorption of water molecules on external surfaces owing to the hydrophilic surfaces. Interlayer water was also quantified from water vapor isotherm, X-ray diffraction (XRD), and thermal gravimetric analyses (TGA) data, displaying nonreversible swelling/shrinkage behavior in response to drying/rewetting cycles. From this quantification and balance of water distribution, we were able to explain most of the widely dispersed data already published according to the various relative humidity (RH) conditions and measurement techniques. Stoichiometric formulas were proposed for the different CSH samples analyzed (0.6 < Ca/Si < 1.6), considering the interlayer water contribution.

[Impact of headache among studied military population in Afghanistan deployed in the Kabul military field hospital]. / Impact des céphalées parmi le personnel militaire déployé au sein de l'hôpital médico-chirurgical de Kaboul.

INTRODUCTION: Headaches are a common reason for consultation with a prevalence of 30%. Few data exist for military personnel, including in situations of war operations. The main objective of this work was to measure the evolution of the impact of headache in such a context. MATERIALS AND METHODS: Two hundred and one personnel deployed in the Kaïa military field hospital in Afghanistan were recruited. A questionnaire designed to recognize headaches, supported by two quality of life scales (MIDAS and HIT-6) and a stress questionnaire were filled out before departure and upon return from missions. DISCUSSION: Sixty-three patients with headache were initially identified, of whom 52 remained symptomatic during the mission. The average total score of MIDAS before departure was 4 days and fell to 1.4 days upon return, with a mean measured change of 3.3 days. For HIT-6, the mean total score was 51.2 points initially and 51.9 points at the end of the mission with a mean change of-0.3 points. Nine patients without headache initially became symptomatic: MIDAS and HIT-6 were not affected. CONCLUSION: Thus, the impact of headache in the particular context of presence in a theater of operations was low: improved MIDAS score and the lack of influence on the HIT-6 score are underlined.

Outbreak of autoimmune disease in silicosis linked to artificial stone.

BACKGROUND: There is a well-established association between inhalational exposure to silica and autoimmune disease. We recently observed an outbreak of silica-related autoimmune disease among synthetic stone construction workers with silicosis referred for lung transplantation assessment. AIMS: To characterize the rheumatologic complications in silicosis within these highly exposed, clinically well-characterized patients. METHODS: We systematically reviewed data from all cases of silicosis due to synthetic stone dust referred to our pulmonary institute for lung transplant assessment, which represents the national centre for all such referrals. In addition to silicosis-specific data, we extracted data relevant to the clinical and serological manifestations of autoimmune diseases present in these patients. RESULTS: Of 40 patients in our advanced silicosis national data, we identified nine (23%) with findings consistent with various autoimmune diseases. Among these nine, three also had findings consistent with pulmonary alveolar proteinosis. Based on an expected autoimmune disease prevalence of 3% (based on the upper-end estimate for this group of diseases in European international data), the proportion of disease in our group represents a >7-fold excess (prevalence ratio 7.5; 99% confidence interval 2.6-16.7). CONCLUSIONS: These cases underscore the strong link between silicosis and multiple distinct syndromes of autoimmune diseases. Vigilance is warranted for the recognition of autoimmune complications in persons with known silicosis; so too is consideration of the occupational exposure history in persons presenting with manifestations of autoimmune disease.

All-trans-retinoic acid regulates aquaporin-3 expression and related cellular membrane permeability in the human amniotic environment.

INTRODUCTION: The aquaporins (AQP1, 3, 8, 9 and 11) are known to be expressed, and involved in the transport of water and small molecules through fetal membranes. To exert these crucial functions, these AQPs have to be finely regulated. All-trans-retinoic acid (atRA) was previously found to regulate some genes in this environment, raising the question of whether these AQPs were regulated by atRA. METHODS: Explants, and primary and established amniotic cells were cultured to determine which AQP were transcriptionally modified by atRA, using the qRT-PCR strategy. Immunohistochemistry and glycerol uptake tests were used to determine the impact of atRA on AQP protein expression and function. Specific agonists of retinoic acid receptors were used to identify the molecular mechanisms of AQP promoter activation. A classical gene AQP promoter study was also used to identify DR5 retinoic acid receptor elements (RAREs). RESULTS: Beyond these AQPs, only one specific atRA-dependent increase in AQP3 transcripts and proteins level was established in amnion (not in chorion) and in related primary and established cells. We found three DR5-RAREs essential for inducing this transcriptional AQP3 through RARα. This transactivation of the AQP3 coding gene was functionally related to an increase of AQP3 permeability tests by a glycerol uptake assay. DISCUSSION: Our data support an atRA regulatory model of AQP3 expression leading to an increased cellular permeability in the epithelial amniotic environment. We cast new light on AF regulation in healthy pregnancy, and advance new hypotheses for obstetrical complications linked to impairment of the retinoic signaling pathway.

A midstream urine collector is not a good alternative to a sterile collection method during the diagnosis of urinary tract infection.

AIM: Guidelines recommend collecting urine with suprapubic aspiration or urethral catheterisation in infants with a suspected urinary tract infection (UTI), but the invasiveness of these methods continues to drive research on new urine collection devices. We studied children with a suspected UTI, who had not been toilet trained, to compare a new midstream urine collector and catheterisation. METHOD: During this prospective controlled diagnosis study of 94 children, urine collection was performed using the midstream collector and then controlled via catheterisation when the urine dipstick was positive. RESULTS: When end stream samples collected by the midstream collector were compared to catheter samples, the results were inconsistent in 23.4% of cases, similar to the inconsistent results between first stream samples discarded by the device and the catheter samples (21.3%). Interestingly, the overall rate of sample contamination in the bag of the midstream collector was lower than that reported in previously published studies and there were no false positive bag results. CONCLUSION: The midstream collector did not appear to provide additional benefits to classic collection bags. A sterile collection method, such as suprapubic aspiration, catheterisation or clean catch, is still mandatory for diagnosing urinary tract infections in children who are not toilet trained.

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

BACKGROUND: The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). AIMS: To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. METHODS: We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. RESULTS: Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). CONCLUSION: Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use.

Totally extraperitoneal (TEP) endoscopic inguinal hernia repair with TAP (transversus abdominis plane) block as a day-case: a prospective cohort study.

BACKGROUND: Totally extraperitoneal (TEP) endoscopic inguinal hernia repair is indicated for recurrent and bilateral inguinal hernias and traditionally is performed under general anesthesia. However, interventions that minimize pain and reduce opioid consumption have certain advantages for patients by avoiding side effects such as nausea and vomiting. The transversus abdominis plane (TAP) block has been used to minimize pain in a diverse range of surgical procedures but its safety on patients undergoing TEP repair has yet to be investigated. AIM: To assess the results of outpatient TEP repair with TAP block without curare. METHODS: Consecutive patients undergoing elective TEP procedure were prospectively enrolled. Patients in two institutes received a similar anesthetic, surgical, and analgesic treatment protocol. RESULTS: Fifty consecutive day-case patients were included in this series. The TEP repair was successful in 49 patients and there was one conversion to transabdominal pre-peritoneal (TAPP) endoscopic inguinal hernia repair. The mean duration of surgery was 20min for unilateral hernia and 40min for bilateral hernia. CONCLUSION: These preliminary results suggest that day-case endoscopic hernia repair (TEP) with TAP block without curare is effective, safe, reproducible and can be proposed in all patients.