Since the first description of mechanical ventilation, our understanding of the positive and negative effects of this form of life support has continued to evolve. To maintain "normal" aeration of the lungs and "normal" blood gas measurements, patients often require much higher airway pressures and tidal volumes than would be expected in a healthy, spontaneously breathing adult. In the early days of mechanical ventilation, the goal was to normalize the blood gas levels, but over the last several decades, we have developed a much better appreciation for the deleterious effects of mechanical ventilation. We have found that lower tidal volumes, which may actually worsen oxygenation and reduce clearance of CO2, can decrease the level of harm caused by mechanical ventilation. This scenario is best described and agreed upon in the setting of ARDS, but a growing body of evidence suggests that the use of higher tidal volumes is harmful in patients with normal lungs undergoing general anesthesia or in patients with lung diseases other than ARDS requiring mechanical ventilation. Finally, the concept of self-induced lung injury has emerged as a mechanism through which patients generating large negative intrathoracic pressures to achieve larger tidal volumes can contribute to worsened lung injury. Given a growing supportive evidence base, we suggest that efforts be made to achieve low tidal volume ventilation in all patients with lung injury or undergoing mechanical ventilation for any reason.

Chronic inflammatory diseases of the lung are often life-threatening and are a leading cause of morbidity in our communities. MicroRNAs (miRs) are now recognized to play critical roles in a wide range of cellular functions, including the regulation of immunologic processes, which are often dysregulated in chronic respiratory diseases. These small noncoding RNA molecules regulate networks of genes by inhibiting translation through the targeting of one or multiple messenger RNA transcripts. This review highlights discoveries that identify important roles for miRs in the regulation of specific pathogenic features of a range of diseases. Furthermore, experimental evidence suggests that pharmacologic inhibition of miR function or delivery of mimics may have therapeutic potential. The review also therefore discusses the potential utility and limitations of therapeutically targeting these molecules and their downstream pathways.

Point-of-care ultrasonography is a key skill for the critical care clinician and is gaining widespread acceptance by clinicians in all areas of medicine. In addition to mastery of image acquisition, image interpretation, and clinical application, intensivists need to be adept with billing for their scanning activity. This article summarizes the requirements for documentation and image storage that must be met to obtain reimbursement for point-of-care ultrasonography services.

The direct-acting oral anticoagulants (DOACs) have been increasingly used over vitamin K antagonists in recent years because they do not require monitoring and have an immediate anticoagulation effect. In general, DOACs have exhibited a better safety profile and noninferiority for prophylaxis and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation compared with vitamin K antagonists in the non-ICU population; whether this finding holds true in patients who are critically ill remains unknown. The current review addresses the role of DOACs in special ICU populations, use of these agents for VTE prophylaxis, perioperative management of DOACs, drug monitoring, and potential drug interactions of DOACs in critically ill patients. Adverse events and available reversal agents for DOACs are also discussed.

The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety.

The term "broncholithiasis" is defined as the presence of calcified or ossified materials within the tracheobronchial tree. The report of the condition dates back to 300 bc when Aristotle first described a symptom of "spitting of stones." The process of calcification usually starts within either the mediastinal, hilar, or peribronchial lymph nodes. The impetus is typically initiated by a granulomatous process such as TB or histoplasmosis; however, it can also been seen following exposure to other fungal or occupational elements. The exact mechanism of the calcified material (broncholith) entering the endobronchial tree remains unknown. It is hypothesized, however, that the calcified tissues gradually erodes and/or breaks loose in the airways as a result of repetitive movements of respiration or cardiac pulsations. The broncholiths are often found in the airways without any signs of erosion, however. The most common symptoms of broncholithiasis include cough, hemoptysis, and wheezing as a result of irritation of the airways and the surrounding tissues. The diagnosis is typically suspected on chest radiographs and confirmed by using bronchoscopy. Depending on the severity of the disease, management options range from simple observation to surgical resection. Despite the potential for major complications, the overall disease prognosis is good if timely and appropriate management is provided.

COPD, asthma, and cystic fibrosis (CF) are obstructive lung diseases with distinct pathophysiologies and clinical phenotypes. In this paper, we highlight recent advances in our understanding of relationships between clinical phenotypes, host inflammatory response, and lung microbiota in these diseases. Although COPD, asthma, and CF largely have distinct lung microbiota and inflammatory profiles, certain commonalities exist. In all three of these lung diseases, and in healthy persons, anaerobic taxa that are typically associated with oral microbiota (eg, Prevotella species, Veillonella species) are present in the airways and associated with increased host inflammatory response. Similarly, across all three diseases, members of the Proteobacteria phylum are associated with more advanced disease. Finally, we highlight challenges in translating these findings into advances in clinical care, including continued knowledge gaps regarding the causal relationships between host inflammatory response, lung microbiota, medication effects, and clinical phenotypes.

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.

COPD has a substantial burden seen in both patient quality of life and health-care costs. One method of minimizing this burden is the implementation of clinical pathways (CPWs). CPWs bring the best available evidence to a range of health-care professionals by adapting guidelines to a local context and detailing essential steps in care.

Common variable immunodeficiency disorders refer to a relatively common primary immune deficiency group of diseases that present with infectious and inflammatory complications secondary to defects in antibody production and sometimes in cellular immunity. The disorder often presents in middle age or later with recurrent sinopulmonary infections, bronchiectasis, or a plethora of noninfectious complications such as autoimmune disorders, granulomatous interstitial lung disease, GI diseases, malignancies (including lymphoma), and multisystem granulomatous disease resembling sarcoidosis. Infusion of immunoglobulin by IV or subcutaneous is the mainstay of therapy. Management of complications is often difficult as immune suppression may be necessary in these conditions and entails the use of medications and biologicals which may further increase the risk for infections. Specifically, bronchiectasis, granulomatous lymphocytic interstitial lung disease, repeated sinopulmonary infections, and malignancies are sequelae of antibody deficiency that may present to the pulmonologist. This review will provide an updated understanding of the molecular aspects, differential diagnosis, presentations, and the management of common variable immunodeficiency disorders.

Evidence regarding the association between sarcopenia (skeletal muscle depletion) and outcomes in patients with lung cancer varies across studies. We aimed to systematically review the prognostic value of sarcopenia in lung cancer.

Abundant epidemiologic evidence supports an association between idiopathic pulmonary fibrosis (IPF) and lung cancer. Lung tumors in patients with IPF develop preferentially in the periphery immediately adjacent to fibrotic areas, with different histologic distribution and immunohistochemical features compared with non-IPF-associated lung tumors. In this context, evidence indicates that IPF and lung cancer share many pathogenic similarities including genetic and epigenetic markers. It has been suggested that specific germline mutations predispose toward both IPF and lung cancer, leading to imbalance between oncogenes and tumor suppressor genes and ultimately carcinogenesis within fibrotic lungs. Aberrant epigenetic regulation due to methylation, histone modifications, and mainly deregulation of common noncoding RNAs represents a possible pathogenic link between the two disease paradigms. Genetic and epigenetic alterations lead to abnormal activation of common transduction pathways, including Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B, mediating metaplasia and hyperproliferation in alveolar type II epithelial cells. Cellular transformations in the mesenchymal phenotype represent a common link between lung fibrosis and carcinogenesis. In this review we summarize current data on common cellular and molecular pathogenic mechanisms between IPF and lung cancer and highlight promising therapeutic targets for this disease combination.

Burnout syndrome is an increasingly common phenomenon that threatens our critical care workforce and the well-being of its members. Burnout syndrome can be conceived of as a workforce manifestation of chronic workload and workforce capacity imbalance. This study explores the role of workload management tools that can address workload as a complement to the resilience-based countermeasures that seek to increase worker capacity. We were able to use step-wise increments in the volume of documentation-related tasks that occurred at the time of electronic health record (EHR) implementation to investigate the relation of workload and burnout. Specialty-specific increases in the prevalence of self-reported burnout during the era of EHR adoption were compared with increases of the length of documentation created by the corresponding specialists observed prior to and following EHR implementation; a robust direct association was reported. To connect ICU workload to burnout, the number of tasks performed was extracted from the EHR, and we measured the average time that our ICU team members required to complete these tasks. Our ICU workforce efficiency was calculated as the ratio of mandatory task time to scheduled time. Comparing this ratio vs a well-established industrial standard for equipment efficiency made us realize that our average workload seemed excessive and placed our staff at risk of burnout syndrome. It is difficult to conceive that our resilience-based countermeasures to prevent and treat burnout would not be more effective when combined with measures that reduce the time our staff members spend on mandatory ICU tasks.

Group 2 innate lymphoid cells (ILC2s) are increasingly recognized as a key controller of type 2 inflammation, and are well known to be highly elevated in human airway type 2 inflammatory diseases including allergic rhinitis, chronic rhinosinusitis with nasal polyps, and asthma. ILC2-mediated production of type 2 cytokines initiates and amplifies airway inflammation via activation of eosinophils, B cells, mast cells, macrophages, fibroblasts, and epithelial cells in these diseases. ILC2s require at least three major signals to fully activate and robustly produce type 2 cytokines. IL-1 family cytokines (IL-1β, IL-18, IL-33), IL-25, and TNF superfamilies (TNF, TL1A, GITR-L, RANK-L) activate the NF-κB and AP-1 pathways that initiate production of IL-5 and IL-13. Lipid mediators (LTC4, LTD4, PGD2) and neuropeptide NMU promote production of IL-4 through the NFAT pathway. IL-2 and IL-7 family cytokines (IL-2, IL-7, IL-9, TSLP) activate the STAT5 pathway that induces survival of ILC2s and enhances cytokine production. The activation of STAT5 is necessary to potently induce cytokine- and lipid mediator-mediated production of type 2 cytokines. Inhibitory pathways for ILC2s have also become clearer. Type I and II interferons and IL-27 inhibit ILC2 functions through the activation of STAT1. Suppression mediated via β2-adrenergic receptor agonists, PGE2, and PGI2 occurs through cAMP and PKA. Glucocorticoid, testosterone, IL-10, and TGF-β are also able to inhibit ILC2-mediated production of type 2 cytokines. Blockage of ILC2 activators, activation of inhibitory pathways of ILC2s, and suppression of ILC2-mediated pathways including type 2 cytokines (IL-5, IL-13, IL-4Ra) may become therapeutic strategies for airway type 2 inflammatory diseases.

A 76-year-old nonsmoking woman visiting from Honduras for the last 6 months with no known medical history originally presented to the ED complaining of abdominal pain. While in the ED, an incidental right middle lobe collapse was found on CT abdomen scan. Review of systems was positive for a chronic productive cough with white sputum for 3 years. She denied association with fevers, chills, night sweats, hemoptysis, appetite changes, or weight loss.

A 39-year-old female avid marathon runner presented with an abnormal chest radiograph obtained during preoperative evaluation prior to bilateral knee replacement because of osteoarthritis. As shown in Figure 1, chest radiograph revealed a focal nodular opacity in the middle lobe. She did not have any prior imaging for comparison.

Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this high prevalence in asymptomatic as well as symptomatic patients with reduced left ventricular ejection fraction (HFrEF), as well as in those with HF with preserved ejection fraction. The acute pathobiologic consequences of OSA, including exaggerated sympathetic activity, oxidative stress, and inflammation, eventually could lead to progressive left ventricular dysfunction, repeated hospitalization, and excessive mortality. Large numbers of observational studies and a few small randomized controlled trials have shown improvement in various cardiovascular consequences of SDB with treatment. There are no long-term randomized controlled trials to show improved survival of patients with HF and treatment of OSA. One trial of positive airway pressure treatment of OSA included patients with HF and showed no improvement in clinical outcomes. However, any conclusions derived from this trial must take into account several important pitfalls that have been extensively discussed in the literature. With the role of positive airway pressure as the sole therapy for SDB in HF increasingly questioned, a critical examination of long-accepted concepts in this field is needed. The objective of this review was to incorporate recent advances in the field into a phenotype-based approach to the management of OSA in HF.

Pulmonary rehabilitation (PR) improves exercise capacity and quality of life in people with COPD; however, its effect on anxiety and depression symptoms is less clear. Existing data are difficult to apply to clinical PR because of diverse interventions and comparators. This review evaluated the effectiveness of PR on anxiety and depression symptoms in people with COPD.

Correction of intravascular hypovolemia is a key component of the prevention and management of acute kidney injury (AKI), but excessive fluid administration is associated with poor outcomes, including the development and progression of AKI. There is growing evidence that fluid administration should be individualized and take into account patient characteristics, nature of the acute illness and trajectories, and risks and benefits of fluids. Existing data support the preferential use of buffered solutions for fluid resuscitation of patients at risk of AKI who do not have hypochloremia. There is a limited role for albumin, and starches should be avoided. Fluids should only be administered until intravascular hypovolemia has been corrected and euvolemia has been achieved using the minimum amount of fluid required to achieve and maintain euvolemia. Oliguria alone should not be viewed as a trigger for fluid administration. If fluid overload occurs, fluid therapy needs to be discontinued, and fluid removal using diuretic agents or extracorporeal therapies should be considered.