Lung transplantation is now an established treatment for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients.

Recent literature has implicated severe neurologic injuries, such as aneurysmal subarachnoid hemorrhage, as a cause of cardiac dysfunction, impaired hemodynamic function, and poor outcomes. Mechanistic links between the brain and the heart have been explored in detail over the past several decades, and catecholamine excess, neuroendocrine dysfunction, and unchecked inflammation all likely contribute to the pathophysiologic process. Although cardiac dysfunction has also been described in other disease paradigms, including septic shock and thermal injury, there is likely a common underlying pathophysiology. In this review, we will examine the pathophysiology of cardiac dysfunction after neurologic injury, discuss the evidence surrounding cardiac dysfunction after different neurologic injuries, and suggest future research goals to gain knowledge and improve outcomes in this patient population.

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.

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.

In healthy individuals, human rhinovirus (HRV) infections are the major cause of the common cold. These are generally uncomplicated infections except for occasional cases of otitis media or sinusitis. In individuals with asthma, however, HRV infections can have a major impact on disease development and progression. HRV-induced wheezing illnesses in early life are a significant risk factor for subsequent development of asthma, and growing evidence supports a role of recurrent HRV infections in the development and progression of several aspects of airway remodeling in asthma. In addition, HRV infections are one of the most common triggers for acute exacerbations of asthma, which represent a major burden to health-care systems around the world. None of the currently prescribed medications for asthma are effective in preventing or reversing asthma development and airway remodeling or are ideal for treating HRV-induced exacerbations of asthma. Thus, a better understanding of the role of HRV in asthma is important if we are to develop more effective therapies. In the past decade, we have gained new insights into the role of HRV infections in the development and progression of airway remodeling as well as a new appreciation for the proinflammatory and host defense responses to HRV infections that may help to regulate susceptibility to asthma exacerbations. This article reviews the current understanding of the role HRV infections play in the pathogenesis of asthma and identifies possible avenues to new therapeutic strategies for limiting the effects of HRV infections in asthma.

Pediatric OSA can result in significant neurocognitive, behavioral, cardiovascular, and metabolic morbidities. Prompt diagnosis and treatment are, therefore, of paramount importance. The current gold standard for diagnosis of OSA in children is in-laboratory polysomnography (PSG). Home sleep apnea testing has been considered as an alternative as it is potentially more cost effective, convenient, and accessible. This review concentrates mainly on the use of type 2 and 3 portable monitoring devices. The current evidence on the feasibility and diagnostic accuracy of home testing in the diagnosis of pediatric OSA was examined. Overall, the evidence in children is limited. Feasibility studies that have been performed have on the whole shown good results, with several reporting > 90% of their home recordings as meeting predetermined quality criteria regarding signal artifact and minimum recording time. The limited data comparing type 2 studies with in-laboratory PSG have shown no significant differences in respiratory parameters. The results pertaining to diagnostic accuracy of type 3 home sleep apnea testing devices are conflicting. Although more research is needed, home testing with at least a type 3 portable monitor offers a viable alternative in the diagnosis of otherwise healthy children with moderate to severe OSA, particularly in settings where access to polysomnography is scarce or unavailable. Of note, since most studies have been performed in habitually snoring healthy children, home sleep apnea testing may not be applicable to children with other comorbid conditions. In particular, CO2 monitoring is important in children in whom there is concern regarding nocturnal hypoventilation, such as children with neuromuscular disease, underlying lung disease, or obesity hypoventilation, and most home testing devices do not include a transcutaneous or end-tidal CO2 channel.

Since pulmonary nontuberculous mycobacteria (PNTM) lung disease was last reviewed in CHEST in 2008, new information has emerged spanning multiple domains, including epidemiology, transmission and pathogenesis, clinical presentation, diagnosis, and treatment. The overall prevalence of PNTM is increasing, and in the United States, areas of highest prevalence are clustered in distinct geographic locations with common environmental and socioeconomic factors. Although the accepted paradigm for transmission continues to be inhalation from the environment, provocative reports suggest that person-to-person transmission may occur. A panoply of host factors have been investigated in an effort to elucidate why infection from this bacteria develops in ostensibly immunocompetent patients, and there has been clarification that immunocompetent patients exhibit different histopathology from immunocompromised patients with nontuberculous mycobacteria infection. It is now evident that Mycobacterium abscessus, an increasingly prevalent cause of PNTM lung disease, can be classified into three separate subspecies with differing genetic susceptibility or resistance to macrolides. Recent publications also raise the possibility of improved control of PNTM through enhanced adherence to current treatment guidelines as well as new approaches to treatment and even prevention. These and other recent developments and insights that may inform our approach to PNTM lung disease are reviewed and discussed.

Pathophysiologic gaps in the actions of currently available treatments for asthma and COPD include neutrophilic inflammation, airway remodeling, and alveolar destruction. All of these processes can be modulated by cyclic adenosine monophosphate-elevating prostaglandins E2 and I2 (also known as prostacyclin). These prostanoids have long been known to elicit bronchodilation and to protect against bronchoconstriction provoked by a variety of stimuli. Much less well known is their capacity to inhibit inflammatory responses involving activation of lymphocytes, eosinophils, and neutrophils, as well as to attenuate epithelial injury and mesenchymal cell activation. This profile of actions identifies prostanoids as attractive candidates for exogenous administration in asthma. By contrast, excessive prostanoid production and signaling might contribute to both the increased susceptibility to infections that drive COPD exacerbations and the inadequate alveolar repair that characterizes emphysema. Inhibition of endogenous prostanoid synthesis or signaling, thus, has therapeutic potential for these types of patients. By virtue of their pleiotropic capacity to modulate numerous pathophysiologic processes relevant to the expression and natural history of airway diseases, prostanoids emerge as attractive targets for therapeutic manipulation.

Critical care transesophageal echocardiography (TEE) is useful in characterizing shock states encountered by intensivists when transthoracic echocardiography (TTE) gives insufficient information or when more detailed analysis of cardiac structures is needed. It is safe, feasible, and easy to learn and is a recommended component of advanced critical care echocardiography. This article reviews critical care TEE regarding training, equipment, comparison with TTE, indications, safety, and standard views of critical care TEE. It should be considered a companion article to a recent two-part series in CHEST that focused on advanced critical care TTE. Included with this article is an online supplement that has a representative series of critical care TEE images with clinical commentary.

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

The Chiari 1 malformation is characterized by > 5-mm herniation of the cerebellar tonsils through the foramen magnum. Consequent compression of the brain stem and nearby neuronal structures involved in respiratory control and maintenance of pharyngeal wall muscle tone may result in respiratory changes during sleep. These changes include respiratory failure and arrest, as well as sleep-related breathing disorders (ie, OSA and central sleep apnea). Although data have accrued on the significance of sleep-related breathing disorders in patients with the Chiari 1 malformation, many management questions remain unanswered. This article reviews the available literature on prevalence and management of sleep-related breathing disorders in patients with the Chiari 1 malformation.

The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassification distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1. Sleepiness can be treated with modafinil/armodafinil or sympathomimetic CNS stimulants, which have been shown to be beneficial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is effective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are needed. Emerging treatments for sleepiness include histamine H3 antagonists (eg, pitolisant) and possibly negative allosteric modulators of the gamma-aminobutyric acid-A receptor (eg, clarithromycin and flumazenil).

Idiopathic pulmonary fibrosis (IPF) is strongly associated with advanced age. Making an accurate diagnosis of IPF is critical, as it remains only one of many potential diagnoses for an elderly patient with newly recognized interstitial lung disease. Optimal management of IPF, especially in older-aged patients, hinges on such factors as balancing the application of standard-of-care measures with the patient's overall health status (robustness vs frailty) and considering the patient's wishes, desires, and expectations. IPF is known to be associated with certain comorbidities that tend to be more prevalent in the elderly population. Until recently, options for the pharmacologic management of IPF were limited and included therapies such as immunosuppressive agents, which may pose substantial risk to the elderly patient. However, the antifibrotic agents pirfenidone and nintedanib have now become commercially available in the United States for the treatment of IPF. The monitoring and treatment of patients with IPF, especially elderly patients with comorbid medical conditions, require consideration of adverse side effects, the avoidance of potential drug-drug interactions, treatment of comorbidities, and the timely implementation of supportive and palliative measures. Individualized counseling to guide decision-making and enhance quality of life is also integral to optimal management of the elderly patient with IPF.

Smoking-induced lung diseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs-depending on the signaling pathway (nuclear factor-κB, adenosine monophosphate-activated protein kinase, c-Jun N-terminal kinase, p38, and signal transducer and activator of transcription 3) activated. Multiple proteins are upregulated and secreted in response to CS exposure, and many of these have immunomodulatory activities that contribute to disease pathogenesis. In particular, metalloproteases 9 and 12, surfactant protein D, antimicrobial peptides (LL-37 and human β defensin 2), and IL-1, IL-6, IL-8, and IL-17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking-induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases.

After a patient encounter, the physician uses two coding systems to bill for the service rendered to the patient. The Current Procedural Terminology (CPT) code is used to describe the encounter or procedure. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code is used to describe the diagnosis(es) of the patient. On October 1, 2015, ICD-9-CM coding will end, and all physicians will be required to use a new diagnostic coding system, the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). This article describes the new diagnostic coding system and how it differs from the old system. There are resources and costs involved for physicians and physician practices to prepare properly for ICD-10-CM. Similar to other important events, the more thorough the preparation, the more likely a positive outcome will occur. Resource use is very important in preparation for the transition from ICD-9-CM to ICD-10-CM. Greater familiarity with ICD-10-CM plus a thorough, effective preparation will lead to reduced costs and a smooth transition. Coding descriptor changes and additional codes occur in ICD-10-CM for chronic bronchitis and emphysema, asthma, and respiratory failure. These changes will affect the coding of these diseases and disorders by physicians. Because the number of codes will increase more than fivefold, the complexity of documentation to support ICD-10-CM will increase substantially. The documentation in the patient's chart to support the ICD-10-CM codes used will need to be enhanced. The requirement for accurate and comprehensive documentation cannot be emphasized enough. All of the coding and documentation changes will be a challenge to pulmonary, critical care, and sleep physicians. They must be prepared fully when ICD-10-CM coding begins and ICD-9-CM coding stops abruptly on October 1, 2015.