Over the last decade, several studies have suggested that survival rates for patients with acute lung injury (ALI) or ARDS may have improved. We performed a systematic analysis of the ALI/ARDS literature to document possible trends in mortality between 1994 and 2006.

Patient-focused sedation and analgesia in the ICU encompasses a strategy of comprehensive structured management that matches initial evaluation, monitoring, medication selection, and the use of protocols with patient characteristics and needs. This is best accomplished through interdisciplinary management by physicians, nurses, and pharmacists. An early consideration is that of the potential predisposing and precipitating factors, as well as prior sedative or analgesic use, factors that may influence pharmacologic and supportive therapy. Frequent monitoring with validated tools improves communication among clinicians and plays an important role in detecting and treating pain and agitation while avoiding excessive or prolonged sedation. Patient-focused management encompasses selecting medications best suited to patient characteristics, including the presence of organ dysfunction that may influence drug metabolism or excessive risk for side effects. The use of protocols to optimize drug therapy has emerged as a key component of management, resulting in reductions in the duration of sedation, mechanical ventilation, and ICU length of stay demonstrated with strategies to titrate medications to specific targets, daily interruption of sedation, intermittent rather than continuous therapy, and analgesia-based therapy. While much attention is paid to the initiation and maintenance of therapy, greater emphasis must be placed on careful de-escalation of therapy in order to avoid analgesic or sedative withdrawal. Finally, more work is needed to explore the relationship of critical illness and sedation management with long-term psychological outcomes.

Antineoplastic agent-induced pulmonary toxicity is an important cause of respiratory failure. Although the incidence of antineoplastic agent-induced pulmonary toxicity seems to be low, more cases can be expected, with increasing numbers of patients receiving the new generations of antineoplastic agents. Antineoplastic agents have previously been associated with bronchospasm, hypersensitivity reactions, venous thromboembolism, and pulmonary hemorrhage. Physicians should be aware of the clinical and radiographic presentations of the pulmonary toxicities associated with the newer antineoplastic agents. The approach to diagnosis, risk factors, and possible mechanisms of antineoplastic agent-induced pulmonary toxicity are discussed in this article.

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that is associated with mutations in tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread, and remarkable female gender restriction. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections. Lung function declines at approximately twofold to threefold times the rate of healthy subjects, based on an annual drop in FEV1 of 75 to 120 mL in reported series. The diagnosis of pulmonary LAM can be made on high-resolution CT (HRCT) scan with reasonable certainty by expert radiologists, but generally requires a lung biopsy in cases in which tuberous sclerosis complex, angiomyolipomata, or chylous effusions are absent. The currently available treatment strategies are based on the antagonism of estrogen action, and are empiric and unproven. A trial of bronchodilators is warranted in patients with reversible airflow obstruction seen on pulmonary function testing. Pleurodesis should be performed with the initial pneumothorax, because the rate of recurrence is high. Angiomyolipomas that exceed 4 cm in size are more likely to bleed and should be evaluated for embolization. Air travel is well-tolerated by most patients with LAM. Lung transplantation is an important option for LAM patients, and can be safely performed by experienced surgeons despite prior unilateral or bilateral pleurodesis in most patients. Women with unexplained recurrent pneumothorax, tuberous sclerosis, or a diagnosis of primary spontaneous pneumothorax or emphysema in the setting of limited or absent tobacco use should undergo HRCT scan screening for LAM. Multicenter clinical trials based on several well-defined molecular targets are currently underway in the United States and Europe.

Type 2 diabetes is a major public health concern with high morbidity, mortality, and health-care costs. Recent reports have indicated that the majority of patients with type 2 diabetes also have obstructive sleep apnea (OSA). There is compelling evidence that OSA is a significant risk factor for cardiovascular disease and mortality. Rapidly accumulating data from both epidemiologic and clinical studies suggest that OSA is also independently associated with alterations in glucose metabolism and places patients at an increased risk of the development of type 2 diabetes. Experimental studies in humans and animals have demonstrated that intermittent hypoxia and reduced sleep duration due to sleep fragmentation, as occur in OSA, exert adverse effects on glucose metabolism. Based on the current evidence, clinicians need to address the risk of OSA in patients with type 2 diabetes and, conversely, evaluate the presence of type 2 diabetes in patients with OSA. Clearly, there is a need for further research, using well-designed studies and long-term follow-up, to fully demonstrate a causal role for OSA in the development and severity of type 2 diabetes. In particular, future studies must carefully consider the confounding effects of central obesity in examining the link between OSA and alterations in glucose metabolism. The interactions among the rising epidemics of obesity, OSA, and type 2 diabetes are likely to be complex and involve multiple pathways. A better understanding of the relationship between OSA and type 2 diabetes may have important public health implications.

Patients with cystic fibrosis (CF) experience declining pulmonary function related to chronic airway inflammation, which results from epithelial and immune cell secretion of proinflammatory mediators that promote neutrophil influx into the airways. This inflammatory response may be disproportionate to the inciting infectious stimulus, resulting in an overly exuberant influx of neutrophils. The neutrophils release proteases, including neutrophil elastase, that eventually overwhelm the antiprotease capacity of the lung and cleave structural proteins, leading to bronchiectasis. This deleterious inflammatory process in patients with CF has become a potential therapeutic target, though the development of effective antiinflammatory therapies has been limited by the lack of sensitive outcome measures. Historically, indirect measures of lung disease, such as spirometry, have been used to assess the effect of antiinflammatory drugs. BAL remains the primary method of interrogating the inflammatory status of the airway, but the procedure is invasive and may eventually be supplanted by induced sputum. Anatomic imaging with high-resolution CT scanning is used clinically, but has unknown utility, and functional imaging, using positron emission tomography, appears promising but is still investigational. Despite the paucity of outcome measures, clinical trials of antiinflammatory agents, including corticosteroids and ibuprofen, have demonstrated benefits, though their use has been limited by adverse effects. Azithromycin is increasingly used as an immunomodulatory agent, although its mechanism of action remains unclear. Strategies for modulating the airway inflammation in patients with CF are currently under development and may offer new therapeutic options for these patients.

Systemic lupus erythematosus (SLE) is considered the archetypal systemic autoimmune disease. Clinically characterized by multisystem involvement and varied serologic abnormalities, no two patients present or have disease that evolves in exactly the same way. Viewed histologically, SLE is characterized by some combination of inflammation and fibrosis, and the clinical phenotype is dictated by the relative contributions of each and the organs affected. Tissue injury appears to be mediated by characteristic autoantibody production, immune complex formation, and their organ-specific deposition. As expected in a multisystem disease, the entire pulmonary system is vulnerable to injury. Any of its compartments-airways, lung parenchyma, vasculature, pleura, or the respiratory musculature-may be independently or simultaneously affected. This article offers the reader a comprehensive review of the numerous pulmonary and thrombotic manifestations of SLE and suggests approaches to their management.

During flexible fiberoptic bronchoscopy (FB), a solitary pulmonary nodule (SPN) is sampled by means of transbronchial needle aspiration (TBNA), brush, or transbronchial lung biopsy under fluoroscopy; and mediastinal lymph nodes are sampled using "blind" TBNA. Endobronchial ultrasound (EBUS) was developed to help visualize the lesion at the time of biopsy in order to improve the diagnostic yield.

Fluid infusion may be lifesaving in patients with severe sepsis, especially in the earliest phases of treatment. Following initial resuscitation, however, fluid boluses often fail to augment perfusion and may be harmful. In this review, we seek to compare and contrast the impact of fluids in early and later sepsis; show that much fluid therapy is clinically ineffective in patients with severe sepsis; explore the detrimental aspects of excessive volume infusion; examine how clinicians assess the intravascular volume state; appraise the potential for dynamic indexes to predict fluid responsiveness; and recommend a clinical approach.

Nontuberculous mycobacteria (NTM) are increasingly associated with pulmonary disease. This is a worldwide phenomenon and one that is not related just to better diagnostic techniques or HIV infection. The mode of transmission of NTM is not well defined, but environmental exposure may be the major factor. While most exposed and infected individuals never acquire NTM disease, some ostensibly immunocompetent persons will. Although our understanding of the pathogenesis of NTM disease is incomplete, we believe that both host and mycobacterial factors are involved. Among the former, interferon-gamma"trafficking" may well play a central role. When disease occurs, it is likely to present in one of three prototypical forms: a tuberculosis-like pattern often affecting older male smokers with COPD; nodular bronchiectasis classically occurring in middle-aged or older women who never smoked and present with cough; and hypersensitivity pneumonitis following environmental exposure. While Mycobacterium avium complex has been described with all three forms, many other NTM can produce one or another of them; variants of these prototypes also exist. Diagnosis of NTM disease relies on microbiology and chest CT scanning, and criteria to aid diagnosis are available. Treatment of disease depends on the species involved, extent and form of disease, and overall condition of the patient. Surgery for localized disease may be useful for those species expected to be refractory to medical therapy. Observation without treatment may be appropriate for some patients with slowly progressive disease that is expected to be particularly difficult to treat.

Airway smooth muscle (ASM) plays a central role in regulating bronchomotor tone in patients with asthma. New evidence, however, suggests that ASM may also orchestrate and perpetuate airway inflammation by promoting the recruitment, activation, and trafficking of inflammatory cells in the airways. This review addresses the immunomodulatory function of ASM and highlights how such function may have therapeutic implications in the management of asthma.

Childhood sleep-disordered breathing (SDB) has been known to be associated with health and cognitive impacts for more than a century, and yet our understanding of this disorder is in its infancy. Neuropsychological consequences in children with snoring or subtle breathing disturbances not meeting the traditional definition of sleep apnea suggest that "benign, or primary snoring" may be clinically significant, and that the true prevalence of SDB might be underestimated. There is no standard definition of SDB in children. The polysomnographic technology used in many sleep laboratories may be inadequate to diagnose serious but subtle forms of clinically important airflow limitation. In the last several years, advances in digital technology as well as new observational studies of respiratory and arousal patterns in large populations of healthy children have led to alternative views of what constitutes sleep-related breathing and arousal abnormalities that may refine our diagnostic criteria. This article reviews our knowledge of childhood SDB, highlights recent advances in technology, and discusses diagnostic and treatment strategies that will advance the management of children with pediatric SDB.

Hemodynamic monitoring, a cornerstone in the management of the critically ill patient, is used to identify cardiovascular insufficiency, its probable cause, and response to therapy. Still it is difficult to document the efficacy of monitoring because no device improves outcome unless coupled to a treatment that improves outcome. Several clinical trials have consistently documented that preoptimization for high-risk surgery patients treated in the operating room and early (< 12 h) goal-directed resuscitation in septic patients treated in the emergency department reduce morbidity, mortality, and resource use (costs) when the end points of resuscitation were focused on surrogate measures of adequacy of global oxygen delivery (Do2). The closer the resuscitation is to the insult, the greater the benefit. When resuscitation was started after ICU admission in high-risk surgical patients, reduced length of stay was also seen. The focus of these monitoring protocols is to establish a mean arterial pressure > 65 mm Hg and then to increase Do2 to 600 mL/min/m2 within the first few minutes to hours of presentation. To accomplish these goals, hemodynamic monitoring focuses more on measures of cardiac output and mixed venous oxygen saturation to access adequacy of resuscitation efforts than on filling pressures. Although these protocols reduce mortality and morbidity is selected high-risk patient groups, the widespread use of monitoring-driven treatment protocols has not yet happened, presumably because all studies have been single-center trials using a single, proprietary blood flow-monitoring device. Multicenter trials are needed of early goal-directed therapies for all patients presenting in shock of various etiologies and when the protocol and not the monitoring device is the primary variable.

The debate about how to resolve cases in which patients and families demand interventions that clinicians regard as futile has been in evolution over the past 20 years. This debate can be divided into three generations. The first generation was characterized by attempts to define futility in terms of certain clinical criteria. These attempts failed because they proposed limitations to care based on value judgments for which there is no consensus among a significant segment of society. The second generation was a procedural approach that empowered hospitals, through their ethics committees, to decide whether interventions demanded by families were futile. Many hospitals adopted such policies, and some states incorporated this approach into legislation. This approach has also failed because it gives hospitals authority to decide whether or not to accede to demands that the clinicians regard as unreasonable, when any national consensus on what is a "beneficial treatment" remains under intense debate. Absent such a consensus, procedural mechanisms to resolve futility disputes inevitably confront the same insurmountable barriers as attempts to define futility. We therefore predict emergence of a third generation, focused on communication and negotiation at the bedside. We present a paradigm that has proven successful in business and law. In the small number of cases in which even the best efforts at communication and negotiation fail, we suggest that clinicians should find ways to better support each other in providing this care, rather than seeking to override the requests of these patients and families.

This statement on the management of patients with Duchenne muscular dystrophy (DMD) undergoing procedural sedation or general anesthesia represents the consensus opinion of a multidisciplinary panel convened under the auspices of the American College of Chest Physicians. Expert recommendations on this subject are needed for several reasons. First, patients with DMD have an increased risk of complications when they undergo sedation or general anesthesia. In addition, due to improved cardiopulmonary therapies, patients with DMD are experiencing an unprecedented duration of survival. As a result, it is more common for them to require procedures involving sedation or general anesthesia. The risks related to anesthesia and sedation for DMD patients include potentially fatal reactions to inhaled anesthetics and certain muscle relaxants, upper airway obstruction, hypoventilation, atelectasis, congestive heart failure, cardiac dysrhythmias, respiratory failure, and difficulty weaning from mechanical ventilation. This statement includes advice regarding the highly interrelated areas of respiratory, cardiac, GI, and anesthetic management of patients with DMD undergoing general anesthesia or procedural sedation. The statement is intended to aid clinicians involved in the care of patients with DMD and to be a resource for other stakeholders in this field, including patients and their families. It is an up-to-date summary of medical literature regarding this topic and identifies areas in need of future research.

The last 5 years have brought dramatic changes to the care of patients with severe sepsis. While early diagnosis remains a challenge and, regrettably, a rapid, sensitive, and specific diagnostic test is still lacking, the methods to identify those critically ill patients who are likely to die have become clearer. The presence of multiple organ failure, vasopressor-dependent shock, and high values in formalized scoring methods such as the APACHE (acute physiology and chronic health evaluation) and sequential organ failure assessment systems all have some utility for outcome prediction for groups of patients. Refinements in long-used supportive practices such as lower tidal volume ventilation and enhanced glucose control have improved outcomes. A growing appreciation of the importance of timely provision of antimicrobial therapy, circulatory resuscitation, and activated protein C administration have also improved survival. Optimal treatment candidates for, and the timing and dose of some treatments (eg, corticosteroids) remain controversial and are undergoing additional study. Perhaps the most important change in the care of patients with severe sepsis is awareness that the syndrome is more common, lethal, and expensive, than previously appreciated, and as such it warrants an organized approach to care provided by experts. Although there is still much to learn, numerous studies now indicate that improvements in outcomes are possible when treatment protocols that incorporate all known beneficial therapies are applied in a timely fashion.

A growing body of basic and clinical science implicates the atypical bacterial pathogens Mycoplasma pneumoniae and Chlamydophila (formerly Chlamydia) pneumoniae as potentially important factors in asthma, although their exact contribution to asthma development and/or persistence remains to be determined. Evidence from human studies links both M pneumoniae and C pneumoniae to new-onset wheezing, exacerbations of prevalent asthma, and long-term decrements in lung function, suggesting that these organisms can play an important role in the natural history of asthma. Furthermore, animal models of acute and chronic infection with these organisms indicate that they have the ability to modulate allergic sensitization and pulmonary physiologic and immune response to allergen challenge. These findings raise the possibility that, in at least some individuals with asthma, antibiotic therapy might have a role in long-term treatment. While antibiotics do not currently have a defined role in the treatment of stable patients with chronic asthma, there is emerging evidence that asthma symptoms and biomarkers of airway inflammation can improve when patients who have atypical bacterial infection as a cofactor in their asthma are treated with macrolide antibiotics. Ongoing research into the importance of atypical pathogens in asthma will further elucidate whether these infections are important in disease development or whether their prevalence is increased in asthmatic subjects due to chronic airway inflammation or other, yet unidentified, predisposing factors. Current studies will further define the role of macrolide antibiotics in the treatment of stable patients with asthma, ultimately determining whether these therapeutic agents have a place in asthma management.

Our understanding of asthma epidemiology is growing increasingly complex. Asthma outcomes are clearly socially patterned, with asthma ranking as a leading cause of health disparities among minority and low socioeconomic groups. Yet, the increasing prevalence and marked disparities in asthma remain largely unexplained by known risk factors. In the United States, asthma disproportionately affects nonwhite children living in urban areas and children living in poverty. Low socioeconomic status (SES), ethnic minority group status, and residence in an inner-city environment are closely intertwined in the United States, making it a challenge to fully disentangle the independent effects of each of these characteristics on asthma morbidity. In addition, studies show geographic variation in asthma outcomes across large cities and neighborhoods within cities that cannot be explained by economic factors alone. Although more limited data are available, studies in rural areas also suggest the stratification of risk based on SES and the proportion of minorities. Among low-SES areas, those with predominantly minority, segregated populations seem especially burdened. Marginalized populations of lower socioeconomic position are disproportionately exposed to irritants (eg, tobacco smoke), pollutants (eg, diesel-related particles), and indoor allergens (eg, cockroach and mouse allergen). Moreover, these marginalized individuals may also live in communities that are increasingly socially toxic, which, in turn, may be related to the increased experience of psychosocial stress that may influence asthma morbidity. Epidemiologic trends suggest that asthma may provide an excellent paradigm for understanding the role of community-level contextual factors in disease. Specifically, a multilevel approach that includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that, to date, remain largely unexplained. Traditionally, asthma epidemiology has focused on individual-level risk factors and family factors. Far less attention has been given to the broader social context in which individuals live. A multilevel approach that explicitly recognizes the embedding of asthma within its biological, psycho-socioeconomic, environmental, and community contexts, is likely to provide a better understanding of asthma disparities at different stages in the life course. Is it simply asthma disparities or is it social disparities in asthma?

Although policies promoting asthma-friendly communities should reduce asthma disparities, not much is known about the status of policy implementation or effectiveness. We review the efforts of state and local agencies to identify and target asthma disparities for reduction, as evidenced by written laws and policy documents and use of funding. Policies targeting health care, homes, schools, and workplaces hold promise for creating asthma-friendly communities; however, the scope and reach of these activities must be increased to have statewide or national impact. In addition, there is a general lack of systematic review of evidence about the institutionalization of successful demonstration programs into policy.