Throughout the industrialized world, nearly one in five employees works some form of nontraditional shift. Such shift work is associated with numerous negative health consequences, ranging from cognitive complaints to cancer, as well as diminished quality of life. Furthermore, a substantial percentage of shift workers develop shift work disorder, a circadian rhythm sleep disorder characterized by excessive sleepiness, insomnia, or both as a result of shift work. In addition to adverse health consequences and diminished quality of life at the individual level, shift work disorder incurs significant costs to employers through diminished workplace performance and increased accidents and errors. Nonetheless, shift work will remain a vital component of the modern economy. This article reviews seminal and recent literature regarding shift work, with an eye toward real-world application in clinical and organizational settings.

Control of ventilation occurs at different levels of the respiratory system through a negative feedback system that allows precise regulation of levels of arterial carbon dioxide and oxygen. Mechanisms for ventilatory instability leading to sleep-disordered breathing include changes in the genesis of respiratory rhythm and chemoresponsiveness to hypoxia and hypercapnia, cerebrovascular reactivity, abnormal chest wall and airway reflexes, and sleep state oscillations. One can potentially stabilize breathing during sleep and treat sleep-disordered breathing by identifying one or more of these pathophysiological mechanisms. This review describes the current concepts in ventilatory control that pertain to breathing instability during wakefulness and sleep, delineates potential avenues for alternative therapies to stabilize breathing during sleep, and proposes recommendations for future research.

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.

Despite recent clinical guideline development, the best pathway of care for children with symptoms of obstructive sleep-disordered breathing (oSDB) is still debated. This systematic review aims to map the research in childhood oSDB that has been conducted so far to support further guideline development, identify evidence gaps, and guide future research.

CPAP is the first-line treatment for moderate to severe OSA syndrome. Up to 25% of patients with OSA syndrome discontinue CPAP treatment due to side effects. Unintentional leakage and its associated annoying consequences are the most frequently reported adverse effects of CPAP. Successive technological improvements have not succeeded in addressing this issue. A systematic review was conducted (1) to assess the impact of different technological advances on unintentional leaks and (2) to determine if any patient characteristics have already been identified as determinants of unintentional leakage. No CPAP modality was superior to another in reducing unintentional leaks and, surprisingly, oronasal masks were associated with higher unintentional leaks. Nasal obstruction, older age, higher BMI, central fat distribution, and male sex might be associated with an increased risk of unintentional leakage. Such leaks remain an important problem. Further studies are needed to improve the understanding of underlying clinical factors so that patients at risk of unintentional leaks may be identified and individualized solutions applied.

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed.

Cough is a common symptom experienced by athletes, particularly after exercise. We performed a systematic review to assess the following in this population: (1) the main causes of acute and recurrent cough, either exercise-induced or not, (2) how cough is assessed, and (3) how cough is treated in this population. From the systematic review, suggestions for management were developed.

The indwelling pleural catheter (IPC), which was initially introduced for the management of recurrent malignant effusions, could be a valuable management option for recurrent benign pleural effusion (BPE), replacing chemical pleurodesis. The purpose of this study is to analyze the efficacy and safety of IPC use in the management of refractory nonmalignant effusions.

Neuromuscular blockings agents (NMBAs) have a controversial role in the ventilatory and medical management of critical illness. The clinical concern surrounding NMBA-induced complications stems from evidence presented in the 2002 clinical practice guidelines, but new evidence from subsequent randomized trials and studies provides a more optimistic outlook about the application of NMBAs in the ICU. Furthermore, changes in the delivery of critical care, such as protocolized care pathways, minimizing or interrupting sedation, increased monitoring techniques, and overall improvements in reducing immobility, have created a modern, 21st century ICU environment whereby NMBAs may be administered safely. In this article we start with a review of the mechanism of action, side effects, and pharmacology of commonly used NMBAs. We then address the rationale for NMBA use for an expanding number of indications (endotracheal intubation, acute respiratory distress syndrome, status asthmaticus, increased intracranial and intra-abdominal pressure, and therapeutic hypothermia after cardiac arrest), with an emphasis on NMBA use in facilitating lung-protective ventilation for respiratory failure. We end with an appraisal over the importance of monitoring depth of paralysis and the concerns of complications, such as prolonged skeletal muscle weakness. In the context of adequate sedation and analgesia, monitored NMBA use (continuous or bolus administration) can be considered for the small number of clinical indications in critically ill patients for which evidence currently exists.

Some studies suggest that lung ultrasonography could be useful for diagnosing pneumonia; moreover, it has a more favorable safety profile and lower cost than chest radiography and CT. The aim of this study was to assess the accuracy of bedside lung ultrasonography for diagnosing pneumonia in adults through a systematic review and meta-analysis.

An update of evidence-based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator.

Aspiration of a foreign body into the lower airways is a common occurrence and can cause significant morbidity and mortality in humans. Most foreign bodies of the tracheobronchial tree are inanimate. However, the medical literature includes reports of live foreign bodies in the airways. Fish, leeches, and roundworms are the most common live foreign bodies of the lower airways. Fishermen are more prone to experience a live fish aspiration, whereas substandard conditions may expose individuals to leech and roundworm infestations. The dangers of and the approaches to the management of these foreign bodies differ from those associated with aspirated inanimate objects. The focus of this review of the medical literature was on live foreign body aspiration and its management.

This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST).

Inflammation is a hallmark of many airway diseases. Improved understanding of the cellular and molecular mechanisms of airway disease will facilitate the transition in our understanding from phenotypes to endotypes, thereby improving our ability to target treatments based on pathophysiologic characteristics. For example, allergic asthma has long been considered to be driven by an allergen-specific T helper 2 response. However, clinical and mechanistic studies have begun to shed light on the role of other cell subsets in the pathogenesis and regulation of lung inflammation. In this review, we discuss the importance of different lymphocyte subsets to asthma and other airway diseases, while highlighting the growing evidence that asthma is a syndrome that incorporates many immune phenotypes.

The interaction between the airway epithelium and the inhaled environment is crucial to understanding the pathobiology of asthma. Several studies have identified an important role of airway epithelial-derived cytokines, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) in asthma pathogenesis. These cytokines have been described as epithelial-derived alarmins that activate and potentiate the innate and humoral arms of the immune system in the presence of actual or perceived damage. Each of the three epithelial-derived alarmins has been implicated in the pathobiology of inhaled allergen-induced airway responses. The best evidence to date exists for TSLP, in that a human monoclonal antibody, which binds TSLP and prevents its engagement with its receptor, resolves airway inflammation in patients with allergic asthma and attenuates allergen-induced airway responses. Better understanding the roles that the epithelial-derived alarmins play and how they influence airway immune response may allow the development of novel therapeutics for asthma treatment.

COPD is a highly debilitating disease that represents a substantial and growing health burden in women. There is increasing evidence for sex-related differences in COPD risk, progression, and outcomes. However, the disease receives scant attention as a women's health issue. Thus, a multifaceted approach is required to address COPD in women, including greater awareness, minimization of risk, and further elucidation of the sex-specific factors (biological and cultural) that affect risk, disease progression, and treatment success. This article reviews the current literature on the topic and provides suggestions for achieving better outcomes for the millions of women with COPD worldwide.

Right atrial pressure (Pra) is determined by the interaction of the function of the heart as a pump, which is called cardiac function, and the factors that determine the return of blood to the heart, which is called return function. Thus, monitoring Pra or its surrogate, central venous pressure (CVP), can give important insights into mechanisms behind changes in hemodynamic status, responses to interventions, and the likelihood of diagnoses. Examination of the components of the Pra tracing, especially during the ventilator cycle, can also give information about right-sided cardiac diastolic function, the status of the tricuspid valve, volume responsiveness, and the cardiac rhythm. Importantly, the pressure difference from the large venous reservoir to the heart is small, and thus great care must be taken with technical factors that affect the measurement.

Stage classification provides a nomenclature about the anatomic extent of a cancer; a consistent language provides the ability to communicate about a specific patient and about cohorts of patients in clinical studies. This paper summarizes the eighth edition of lung cancer stage classification, which is the worldwide standard as of January 1, 2017. This revision is based on a large global database, a sophisticated analysis, extensive internal validation as well as multiple assessments confirming generalizability. Practicing clinicians must be familiar with the stage classification system when managing contemporary patients with lung cancer.

Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age. In particular, acetate, adenosine, alanine, hippurate, succinate, threonine, and trans-aconitate, and pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were all identified as significant in at least two studies. There were also a number of nonreplicated results; however, the literature is not yet sufficiently developed to determine whether these represent spurious findings or reflect the substantial heterogeneity and limited statistical power in the studies and their methods to date. This review highlights the need for additional asthma metabolomic studies to explore these issues, and, further, the need for standardized methods in the way these studies are conducted. We conclude by discussing the potential of translation of these metabolomic findings into clinically useful biomarkers and the crucial role that integrated omics is likely to play in this endeavor.