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Journal: American journal of respiratory and critical care medicine


Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.


Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.


Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.


Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. The long-term consequences of cleaning agents on respiratory health are, however, not well described.

Concepts: Pulmonology, Respiratory system, Mucus


Population studies suggest improved sepsis outcomes with statins but randomized controlled trials in patients with sepsis and organ dysfunction in critical care settings have broadly been negative. In vitro data suggest statins modulate age-related neutrophil functions improving neutrophil responses to infection, but only in older patients and at high dose.


Rationale: Critically ill patients frequently develop neuropsychological disturbances including acute delirium or memory impairment. The need for mechanical ventilation is as a risk factor for these adverse events, but a mechanism that links lung stretch and brain injury has not been identified. Objetives: To identify the mechanisms that lead to brain dysfunction during mechanical ventilation. Methods: Brains from mechanically ventilated mice were harvested, and signals of apoptosis and alterations in the Akt survival pathway studied. These measurements were repeated in vagotomized or haloperidol-treated mice, and in animals intracerebroventricullarly injected with selective dopamine-receptor blockers. Hippocampal slices were cultured and treated with micromolar concentrations of dopamine, with or without dopamine-receptor blockers. Finally, levels of dysbindin, a regulator of the membrane availability of dopamine receptors, were assessed in the experimental model and in brain samples from ventilated patients. Measurements and Main Results: Mechanical ventilation triggers hippocampal apoptosis as a result of type-2 dopamine receptor activation in response to vagal signaling. Activation of these receptors blocks the Akt/GSK3β prosurvival pathway and activates the apoptotic cascade, as demonstrated in vivo and in vitro. Vagotomy, systemic haloperidol or intracerebroventricular raclopride (a type-2 dopamine receptor blocker) ameliorated this effect. Moreover, ventilation induced a concomitant change in the expression of dysbindin-1C. These results were confirmed in brain samples from ventilated patients. Conclusions: These results prove the existence of a pathogenetic mechanism of lung stretch-induced hippocampal apoptosis that could explain the neurological changes in ventilated patients and may help to identify novel therapeutic approaches.

Concepts: Brain, Signal transduction, Traumatic brain injury, Second messenger system, Dopamine receptor, Antipsychotic, Dopamine, Haloperidol


Over 25 million American children breathe polluted air on diesel school buses. Emission reduction policies exist but the health impacts to individual children have not been evaluated.

Concepts: Petroleum, Pollution, Biofuel, School bus, Air pollution, Chicago, Bus, Diesel engine


Rationale: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource utilisation, allow risk-adjusted comparison of center-specific outcomes and help clinicians to target patients most likely to benefit from ECMO. Objectives: To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. Methods: Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction score (RESP-score) using bootstrapping methodology with internal and external validation. Main results: Of the 2355 patients included in the study, 1338 patients (57%) were discharged alive from hospital. The RESP-score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression which included: age, immunocompromised status, duration of mechanical ventilation prior to ECMO, diagnosis, central nervous system dysfunction, acute associated non-pulmonary infection, neuro-muscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2 and peak inspiratory pressure. The ROC curve analysis of the RESP score was c=0.74, 95% Confidence Interval (0.72 - 0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c=0.92 [95%CI 0.89 - 0.97]). Conclusions: The RESP-score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Concepts: Central nervous system, Nervous system, Regression analysis, Intensive care medicine, Prediction, Prediction interval, Extracorporeal, Extracorporeal membrane oxygenation


RATIONALE: Automated weaning has not been compared to a paper-based weaning protocol in North America. OBJECTIVE: We conducted a pilot randomized trial comparing Automated Weaning and Protocolized Weaning in critically ill adults to evaluate clinician compliance and acceptance of the study protocols, recruitment, and impact on outcomes. METHODS: From August 2007 to October 2009, we enrolled critically ill adults requiring > 24 hours of mechanical ventilation and at least partial reversal of the condition precipitating respiratory failure at 9 Canadian intensive care units. We randomized patients who tolerated at least 30 minutes of pressure support and either failed or were not yet ready to undergo a spontaneous breathing trial to Automated or Protocolized Weaning. Both groups utilized pressure support, included spontaneous breathing trials, used a common PEEP/FiO2 chart, sedation protocol and criteria for extubation, reintubation and noninvasive ventilation. RESULTS: We recruited 92 patients (49 Automated, 43 Protocolized) over 26 months. Adherence to assigned weaning protocols and extreme sedation scale scores fell within prespecified thresholds. Combined physician/RT and RN acceptance scores of the study weaning and sedation protocols, respectively, were not significantly different. Automated Weaning patients had significantly shorter median times to first successful breathing trial (1.0 vs. 4.0 d, p<0.0001), extubation (3.0 vs. 4.0 d, p=0.02), successful extubation (4.0 vs. 5.0 d, p=0.01) and underwent fewer tracheostomies and episodes of protracted ventilation. CONCLUSIONS: Compared to a standardized protocol, Automated Weaning was associated with promising outcomes that warrant further investigation. Minor protocol modifications may increase compliance, facilitate recruitment, and enhance feasibility.

Concepts: Epidemiology, Medical terms, Randomized controlled trial, Intensive care medicine, Mechanical ventilation, Failure, Sedation, Spontaneous breathing trial


RATIONALE: Occupational co-exposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma. OBJECTIVES: To estimate associations between pleural mesothelioma and occupational mineral wool and silica exposure and to study the impact of occupational co-exposure on the risk of pleural mesothelioma. METHODS: 1,199 male cases and 2,379 controls were included in a French pooled case-control study. Complete job histories were collected and occupational exposure to asbestos, mineral wool (MW), and silica were assessed by three French job exposure matrices. Unconditional logistic regression models adjusted for age, birth date, and occupational asbestos exposure were used to estimate odds ratios (OR) and 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: A significant association between mesothelioma and MW exposure was observed after adjustment for occupational asbestos exposure. OR for subjects exposed to less than 0.01 f/ml-y was 1.6 (95% CI: 1.2-2.1) and increased to 2.5 (95% CI: 1.8-3.4) for subjects exposed to more than 0.32 f/ml-y. All ORs for silica exposure were around the null. Co-exposure to either asbestos and MW or asbestos and silica seemed to increase the risk of pleural mesothelioma. ORs were 17.6 (95% CI: 11.8-26.2) and 9.8 (95% CI: 4.2-23.2) for subjects exposed to both asbestos and MW and for subjects exposed to both asbestos and silica, respectively, compared to 4.3 (95% CI: 1.9-9.8) for occupational asbestos exposure alone. CONCLUSION: Our results are in favour of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and MW or asbestos and silica.

Concepts: Regression analysis, Logit, Logistic regression, Epidemiology, Cancer, Mesothelioma, Asbestos, Mineral wool