In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD.

The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small cell lung cancer (NSCLC) has not been well-established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection.

Serum ionized calcium (iCa) is often measured in patients admitted to ICUs, and at least half of these patients will have values outside the reference range during their ICU stay. The vast majority of these patients do not have an underlying disease of calcium homeostasis. This Contemporary Review discusses the rationale for measurement of iCa and whether available data support its measurement and correction. It is determined that while measurement of serum iCa is commonplace and attempted correction is popular, available evidence and logical analysis do not wholly support these practices. Abnormal values of iCa are likely a marker of disease severity in critical illness and most often normalize spontaneously with resolution of the primary disease process. Alternatively, low iCa levels in critical illness may be protective and attempted correction of low levels may be harmful. Dramatic curtailment of iCa measurement and calcium administration in several studies was not associated with worsening outcomes. The absence of high-quality data to guide practice allows for a spectrum of approaches to the measurement and treatment of iCa, but these approaches should be guided by basic principles of rational clinical decision-making. Widespread, protocolized measurement and administration with the simple goal of normalizing values in the name of "euboxia" should be discouraged.

Blood supply of the tracheobronchial tree is derived from a dual system involving pulmonary and bronchial circulation. Various primary and secondary abnormalities of central airway vasculature can present with patterns that are distinct during bronchoscopy. These patterns maybe visualized during bronchoscopic evaluation of a patient with hemoptysis or as an incidental finding during an airway examination for other indications. Thorough knowledge of airway vasculature abnormalities and recognition of possible underlying pathophysiology is vital for the bronchoscopist. This review is a comprehensive description of vascular anatomy of the airway and the different vascular abnormalities that can be encountered during bronchoscopy.

Asthma is characterized by chronic airway inflammation. Fractional exhaled nitric oxide (Feno) has emerged as a marker of T-helper cell type 2-mediated allergic airway inflammation. Recent studies suggest a role for Feno testing as a point-of-care tool in the management of patients with asthma. This Topics in Practice Management article reviews current coverage and reimbursement issues related to Feno testing and provides an overview of pertinent recent studies.

COPD is a significant public health challenge, notably set to become the third leading cause of death and fifth leading cause of chronic disability worldwide by the next decade. Skeletal muscle impairment is now recognized as a disabling, extrapulmonary consequence of COPD that is associated with reduced quality of life and premature mortality. Because COPD typically manifests in older individuals, these clinical features may overlie normal age-associated declines in muscle function and performance. Although physical inactivity, oxidative stress, inflammation, hypoxia, malnutrition, and medications all likely contribute to this comorbidity, a better understanding of the underlying mechanism is needed to develop effective therapies. Mitochondrial alterations have been described; these alterations include reductions in density and oxidative enzyme activity, increased mitochondrial reactive oxygen species production, and induction of muscle proteolysis including autophagy. This review focuses on the perspective that mitochondrial alterations contribute to impaired locomotor muscle performance in patients with COPD by reducing oxidative capacity and thus endurance, as well as by triggering proteolysis and thus contributing to atrophy and weakness. We discuss how the potential underlying mechanisms converge on mitochondria by targeting the peroxisome proliferator-activated receptor γ-coactivator-1α signaling pathway (thereby reducing mitochondrial biogenesis and muscle oxidative capacity and potentially increasing fiber atrophy) and how taking advantage of normal muscle plasticity and mitochondrial biogenesis may reverse this pathophysiology. We propose recent therapeutic strategies aimed at increasing peroxisome proliferator-activated receptor γ-coactivator-1α levels, such as endurance training and exercise mimetic drugs, with the strong rationale for increasing mitochondrial biogenesis and function and thus improving the muscle phenotype in COPD.

Systematic reviews were conducted to examine two related key questions (KQs) in children with chronic (> 4 weeks' duration) wet or productive cough not related to bronchiectasis: KQ1-How effective are antibiotics in improving the resolution of cough? If so, what antibiotic should be used and for how long? KQ2-When should they be referred for further investigations?

In-laboratory, attended polysomnography has long been the gold standard for the diagnosis of sleep-disordered breathing (SDB). In recent years, economic pressures and long wait times have driven interest in home sleep testing, which has, in turn, led to the development of algorithms that bypass the sleep laboratory in favor of portable monitoring studies and in-home initiation of positive airway pressure therapy. For appropriately selected outpatients, evidence is accumulating that portable monitors are a reasonable substitute for in-laboratory polysomnography. In the inpatient setting, in which SDB is both highly prevalent and associated with adverse outcomes in certain populations, the literature is evolving on the use of portable monitors to expedite diagnosis and treatment of SDB. This review discusses society guidelines and recent research in the growing field of portable monitoring.

The COPD Assessment Test (CAT) was developed as a simple instrument to assess health status in patients with COPD. This study aimed to systematically review the determinants of the CAT score, its ability to predict clinical outcomes, and the agreement between CAT (≥ 10) and the modified Medical Research Council scale (mMRC ≥ 2) to categorize patients into the new Global Initiative for Chronic Obstructive Lung Disease classification system.

There is little guidance on what clinicians should do when advance directives (or living wills, specifically) are challenged, particularly when surrogate decision-makers' interpretations of patients' wishes conflict with the living will. In our commentary, we make a controversial argument suggesting that overriding living wills can be ethically preferable to the alternative of strictly adhering to them. We propose four ethical considerations for determining whether it is ethically supportable to override living wills.

Diffuse lung diseases in children, also called children's interstitial lung disease, are a diverse group of rare disorders that cause disturbances of gas exchange in the lungs. Although individually rare, there are many different forms of diffuse lung disease in children, and collectively these disorders are associated with significant morbidity and mortality, as well as health-care resource utilization. Over the past several years, there have been many significant advances in the field, including genetic discoveries and the development of clinical practice guidelines. This review summarizes recent advances in the understanding, diagnosis, and treatment of diffuse lung diseases in children.

Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood. The following review examines recent discoveries in the fields of lung development and tobacco and nicotine exposure, emphasizing studies published within the last 5 years. In utero tobacco and nicotine exposure remains common, occurring in approximately 10% of pregnancies within the United States. Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood. Recently, genomic and epigenetic risk factors, such as alterations in DNA methylation, have been identified that may influence the risk for long-term disease. This review examines the impact of prenatal tobacco and nicotine exposure on lung development with a particular focus on nicotinic acetylcholine receptors. In addition, this review examines the role of prenatal and postnatal tobacco smoke and nicotine exposure and its association with augmenting infection risk, skewing the immune response toward a T-helper type 2 bias and increasing risk for developing an allergic phenotype and asthmalike symptoms during childhood. Finally, this review outlines the respiratory morbidities associated with childhood secondhand smoke and nicotine exposure and examines genetic and epigenetic modifiers that may influence respiratory health in infants and children exposed to in utero or postnatal tobacco smoke.

Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

Several recent cough guidelines have advised consideration of occupational or environmental causes for chronic cough, but it is unclear how frequently this recommendation has been routinely applied. Therefore, we undertook a systematic review to address this aspect.

Corticosteroids are an option in the treatment of community-acquired pneumonia (CAP). However, the benefits and adverse effects of corticosteroids, especially in severe CAP, have not been well assessed.

OSA is a commonly encountered comorbid condition in surgical patients. The risk of cardiopulmonary complications is increased by two to threefold with OSA. Among the different treatment options for OSA, CPAP is an efficacious modality. This review examines the evidence regarding the use of CPAP in the preoperative and postoperative periods in surgical patients with diagnosed and undiagnosed OSA.

Capnography has made steady inroads in the ICU and is increasingly used for all patients who are mechanically ventilated. There is growing recognition that capnography is rich in information about lung and circulatory physiology and provides insight into many diseases and treatments. These include conditions of impaired matching of ventilation and perfusion, such as pulmonary embolism and obstructive lung diseases; circulatory questions, such as the adequacy of chest compressions during cardiac arrest or fluid responsiveness in patients in shock; and the safety of procedural sedation. In this review, we emphasize analysis of the entire capnographic waveform as a way to glean additional useful information. We also discuss important limitations of capnography, especially when it is considered to be a surrogate for Paco2.

Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC.

Balancing population-based efforts to modify the social and environmental factors that promote tobacco dependence with efforts to improve the delivery of case-based treatments is necessary for realizing maximum reductions in the cost and consequences of the disease. Public health antismoking campaigns following the 1964 Surgeon General's report on the health risks of smoking have changed social norms, prevented initiation among youth, and promoted abstinence among the addicted. However, the rate of progress enjoyed to date is unlikely to continue into the coming decades, given that current annual unassisted cessation rates among prevalent smokers remains fairly low. With more than 1 billion patient interactions annually, there is an enormous unrealized capacity for health-care systems to have an effect on this problem. Clinicians report a perceived lack of reimbursement as a significant barrier to full integration of tobacco dependence into health care. A more complete understanding of the coding and documentation requirements for successful practice in this critically important area is a prerequisite to increasing engagement. This paper presents several case-based scenarios illustrating important practice management issues related to the treatment of tobacco dependence in health care.

Potential benefits and possible risks associated with ultrasound guidance compared with traditional palpation for radial artery catheterization are not fully understood.