Chest
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The number of pharmacological medications available to treat patients with COPD has increased over the past few decades. Most of the improvement has come from the modification of older compounds that are now more potent, of longer duration, and delivered in improved devices. They are now available as single, double, and even triple combinations that, although attempting to simplify administration, have also resulted in a large number of preparations. ⋯ The preferred route remains the inhaled direct delivery to the airways, but the favorable results obtained with systemic agents such as macrolides and roflumilast and the preliminary results of some biologicals are opening the door for the development of new drugs or reformulation of medications that have been used for other indications. Perhaps the most pressing need is to study the effect of these agents at early points in the course of the disease, because until now most, if not all, studies have been conducted in patients usually older than age 60 years, when most of the natural course of the disease has already been run. This monograph reviews the available pharmacological therapy based on current evidence and provides practical recommendations to health providers caring for patients with COPD.
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Review
Immune checkpoint immunotherapy for non-small cell lung cancer: benefits and pulmonary toxicities.
Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response. However, this unique mechanism of action has also led to the recognition of class-specific side effects. ⋯ In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.
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The diaphragm is the primary muscle of inspiration. Its capacity to respond to the load imposed by pulmonary disease is a major determining factor both in the onset of ventilatory failure and in the ability to successfully separate patients from ventilator support. It has recently been established that a very large proportion of critically ill patients exhibit major weakness of the diaphragm, which is associated with poor clinical outcomes. ⋯ Loss of force production by the diaphragm under these conditions is caused by a combination of defective contractility and reduced diaphragm muscle mass. Importantly, many of the same molecular mechanisms are implicated in the diaphragm dysfunction associated with both mechanical ventilation and sepsis. This review outlines the primary cellular mechanisms identified thus far at the nexus of diaphragm dysfunction associated with mechanical ventilation and/or sepsis, and explores the potential for treatment or prevention of diaphragm weakness in critically ill patients through therapeutic manipulation of these final common pathway targets.
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Over the past 30 years, hypoglossal nerve stimulation has moved through a development pathway to become a viable treatment modality for patients with OSA. Initial pilot studies in animals and humans laid the conceptual foundation for this approach, leading to the development of fully implantable stimulating systems for therapeutic purposes. These devices were then shown to be both safe and efficacious in feasibility studies. ⋯ Collectively, clinical trials of hypoglossal nerve stimulating systems have yielded important insights that can help optimize therapeutic responses to hypoglossal nerve stimulation. These insights include specific patient selection criteria and methods for delivering stimulation to specific portions of the hypoglossal nerve and/or genioglossus muscle. New approaches for activating efferent and afferent motor pathways are currently in early-stage laboratory development and hold some long-term promise as a novel therapy.
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Atrial fibrillation (AF) is the most common arrhythmia encountered in the ICU. Preexisting AF is highly prevalent among older patients with chronic conditions who are at risk for critical illness, whereas new-onset AF can be triggered by accelerated atrial remodeling and arrhythmogenic triggers encountered during critical illness. The acute loss of atrial systole and onset of rapid ventricular rates that characterize new-onset AF often lead to decreased cardiac output and hemodynamic compromise. ⋯ In addition to acute hemodynamic effects, new-onset AF during critical illness is associated with both short- and long-term increases in the risk of stroke, heart failure, and death, with AF recurrence rates of approximately 50% within 1 year following hospital discharge. In the absence of a strong evidence base, there is substantial practice variation in the choice of strategies for management of new-onset AF during critical illness. We describe acute and long-term evaluation and management strategies based on current evidence and propose future avenues of investigation to fill large knowledge gaps in the management of patients with AF during critical illness.