Respiratory health effects of fifteen years of improved collective protection in a wheat-processing worker population.

INTRODUCTION: Occupational exposure to grain dust causes respiratory symptoms and pathologies. To decrease these effects, major changes have occurred in the grain processing industry in the last twenty years. However, there are no data on the effects of these changes on workers' respiratory health. OBJECTIVES: The aim of this study was to evaluate the respiratory health of grain workers and farmers involved in different steps of the processing industry of wheat, the most frequently used cereal in Europe, fifteen years after major improvements in collective protective equipment due to mechanisation. MATERIALS AND METHOD: Information on estimated personal exposure to wheat dust was collected from 87 workers exposed to wheat dust and from 62 controls. Lung function (FEV1, FVC, and PEF), exhaled nitrogen monoxide (FENO) and respiratory symptoms were assessed after the period of highest exposure to wheat during the year. Linear regression models were used to explore the associations between exposure indices and respiratory effects. RESULTS: Acute symptoms - cough, sneezing, runny nose, scratchy throat - were significantly more frequent in exposed workers than in controls. Increased mean exposure level, increased cumulative exposure and chronic exposure to more than 6 mg.m (-3) of inhaled wheat dust were significantly associated with decreased spirometric parameters, including FEV1 and PEF (40 ml and 123 ml.s (-1) ), FEV1 and FVC (0.4 ml and 0.5 ml per 100 h.mg.m (-3) ), FEV1 and FVC (20 ml and 20 ml per 100 h at >6 mg.m (-3) ). However, no increase in FENO was associated with increased exposure indices. CONCLUSIONS: The lung functions of wheat-related workers are still affected by their cumulative exposure to wheat dust, despite improvements in the use of collective protective equipment.

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation.

Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community-acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.

Auto Poisoning of the Respiratory Chain by a Quorum-Sensing-Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance.

Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum-sensing-regulated low-molecular-weight excreted molecule, triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data identify both a new programmed cell death system and a novel role for HQNO as a critical inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis.

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.

Apnea-like suppression of respiratory motion: First evaluation in radiotherapy.

BACKGROUND AND PURPOSE: Compensation for respiratory motion is needed while administering radiotherapy (RT) to tumors that are moving with respiration to reduce the amount of irradiated normal tissues and potentially decrease radiation-induced collateral damages. The purpose of this study was to test a new ventilation system designed to induce apnea-like suppression of respiratory motion and allow long enough breath hold durations to deliver complex RT. MATERIAL AND METHODS: The High Frequency Percussive Ventilation system was initially tested in a series of 10 volunteers and found to be well tolerated, allowing a median breath hold duration of 11.6min (range 3.9-16.5min). An evaluation of this system was subsequently performed in 4 patients eligible for adjuvant breast 3D conformal RT, for lung stereotactic body RT (SBRT), lung volumetric modulated arc therapy (VMAT), and VMAT for palliative pleural metastases. RESULTS: When compared to free breathing (FB) and maximal inspiration (MI) gating, this Percussion Assisted RT (PART) offered favorable dose distribution profiles in 3 out of the 4 patients tested. PART was applied in these 3 patients with good tolerance, without breaks during the "beam on time period" throughout the overall courses of RT. The mean duration of the apnea-like breath hold that was necessary for delivering all the RT fractions was 7.61min (SD=2.3). CONCLUSIONS: This first clinical implementation of PART was found to be feasible, tolerable and offers new opportunities in the field of RT for suppressing respiratory motion.

Extrafascial injection for interscalene brachial plexus block reduces respiratory complications compared with a conventional intrafascial injection: a randomized, controlled, double-blind trial?.

BACKGROUND: Hemidiaphragmatic paresis after ultrasound-guided interscalene brachial plexus block is reported to occur in up to 100% of patients. We tested the hypothesis that an injection lateral to the brachial plexus sheath reduces the incidence of hemidiaphragmatic paresis compared with a conventional intrafascial injection, while providing similar analgesia. METHODS: Forty ASA I-III patients undergoing elective shoulder and clavicle surgery under general anaesthesia were randomized to receive an ultrasound-guided interscalene brachial plexus block for analgesia, using 20 ml bupivacaine 0.5% with epinephrine 1:200 000 injected either between C5 and C6 within the interscalene groove (conventional intrafascial injection), or 4 mm lateral to the brachial plexus sheath (extrafascial injection). The primary outcome was incidence of hemidiaphragmatic paresis (diaphragmatic excursion reduction >75%), measured by M-mode ultrasonography, before and 30 min after the procedure. Secondary outcomes were forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow. Additional outcomes included time to first opioid request and pain scores at 24 h postoperatively (numeric rating scale, 0-10). RESULTS: The incidences of hemidiaphragmatic paresis were 90% (95% CI: 68-99%) and 21% (95% CI: 6-46%) in the conventional and extrafascial injection groups, respectively (P<0.0001). Other respiratory outcomes were significantly better preserved in the extrafascial injection group. The mean time to first opioid request was similar between groups (conventional: 802 min [95% CI: 620-984 min]; extrafascial: 973 min [95% CI: 791-1155 min]; P=0.19) as were pain scores at 24 h postoperatively (conventional: 1.6 [95% CI: 0.9-2.2]; extrafascial: 1.6 [95% CI: 0.8-2.4]; P=0.97). CONCLUSIONS: Ultrasound-guided interscalene brachial plexus block with an extrafascial injection reduces the incidence of hemidiaphragmatic paresis and impact on respiratory function while providing similar analgesia, when compared with a conventional injection. CLINICAL TRIAL REGISTRATION: NCT02074397.