Extracorporeal membrane oxygenation (ECMO) is a technique for providing life support for patients experiencing both pulmonary and cardiac failure by maintaining oxygenation and perfusion until native organ function is restored. ECMO is used routinely at many specialized hospitals for infants and less commonly for children with respiratory or cardiac failure from a variety of causes. Its usage is more controversial in adults, but select medical centers have reported favorable findings in patients with ARDS and other causes of severe pulmonary failure. ECMO is also rarely used as a rescue therapy in a small subset of adult patients with cardiac failure. This article will review the current uses and techniques of ECMO in the critical care setting as well as the evidence supporting its usage. In addition, current practice management related to coding and reimbursement for this intensive therapy will be discussed.

Central venous pressure (CVP) is used almost universally to guide fluid therapy in hospitalized patients. Both historical and recent data suggest that this approach may be flawed.

Many acute infectious pulmonary diseases have incubation periods that are long enough for travelers to have symptoms after returning home to a health-care system that is not familiar with "foreign" infections. Respiratory infections have a relatively limited repertoire of clinical manifestations, so that there is often nothing characteristic enough about a specific infection to make the diagnosis obvious. Thus, the pathway to the diagnosis of infections that are not endemic in a region relies heavily on taking a thorough history of both itinerary and of specific exposures. One important caveat is that on occasion, the history of a recent trip creates an element of "tunnel vision" in the evaluating health-care provider. It is tempting to relate a person's problem to that recent trip; however, when evaluating recent returnees, it is always important to remember that the travel may have nothing to do with the patient's presentation. Recent travel may add diagnostic considerations to the list of possibilities, but an astute clinician must not disregard the possibility that the patient's illness has nothing to do with the recent trip.

Congestive heart failure (HF), an exceedingly common and costly disease, is frequently seen in association with central sleep apnea (CSA), which often manifests as a periodic breathing rhythm referred to as Cheyne-Stokes respiration. CSA has historically been considered to be a marker of heart disease, since improvement in cardiac status is often associated with the attenuation of CSA. However, this mirroring of HF and CSA may suggest bidirectional importance to their relationship. In fact, observational data suggest that CSA, associated with repetitive oxyhemoglobin desaturations and surges in sympathetic neural activity, may be of pathophysiologic significance in HF outcomes. In light of the disappointing results from the first large trial assessing therapy with continuous positive airway pressure in patients with CSA and HF, further large-scale interventional trials will be needed to assess the role, if any, of CSA treatment on the outcomes of patients with HF. This review will discuss epidemiologic, pathophysiologic, diagnostic, and therapeutic considerations of CSA in the setting of HF.

COPD is highly prevalent and will continue to be an increasing cause of morbidity and mortality worldwide. COPD is now viewed under a new paradigm as preventable and treatable. In addition, it has become accepted that COPD is not solely a pulmonary disease but also one with important measurable systemic consequences. Patients with COPD have to be comprehensively evaluated to determine the extent of disease so that therapy can be adequately individualized. We now know that smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have an impact on mortality. The completion of well-planned pharmacologic trials have shown the importance of decreasing resting and dynamic hyperinflation on patient-centered outcomes and the possible impact on mortality and rate of decline of lung function. In addition, therapy with pulmonary rehabilitation and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, and exercise capacity. Rational use of single or multiple therapeutic modalities in combination have an impact on exacerbations and hospitalizations. This monograph presents an integrated approach to patients with COPD and updates their management incorporating the recent advances in the field. The future for patients with COPD is bright as primary and secondary prevention of smoking becomes more effective and air quality improves. In addition, current research will unravel the pathogenesis, clinical, and phenotypic manifestations of COPD, thus providing exciting therapeutic targets. Ultimately, the advent of newer and more effective therapies will lead to a decline in the contribution of this disease to poor world health.

Recognition of a pivotal role for eicosanoids in both normal and pathologic fibroproliferation is long overdue. These lipid mediators have the ability to regulate all cell types and nearly all pathways relevant to fibrotic lung disorders. Abnormal fibroproliferation is characterized by an excess of profibrotic leukotrienes and a deficiency of antifibrotic prostaglandins. The relevance of an eicosanoid imbalance is pertinent to diseases involving the parenchymal, airway, and vascular compartments of the lung, and is supported by studies conducted both in humans and animal models. Given the lack of effective alternatives, and the existing and emerging options for therapeutic targeting of eicosanoids, such treatments are ready for prime time.

Nocturnal noninvasive ventilation (NNV), the provision of ventilatory assistance via a noninvasive interface mainly during sleep, has assumed an important role in the management of chronic hypoventilatory syndromes. This review focuses on recent developments related to the use of NNV to treat various forms of chronic respiratory failure or insufficiency. In the past, NNV has been used mainly to treat respiratory insufficiency in patients with neuromuscular disease (NMD) or chest wall deformity; it should be instituted when these patients have orthopnea or daytime symptoms associated with nocturnal hypoventilation. An emerging application is to treat obesity-hypoventilation syndrome, particularly in continuous positive airway pressure (CPAP) failures. Additionally, it has a role in managing some patients with obstructive sleep apnea who are hypoventilating or find the lower expiratory pressure with bilevel positive pressure ventilators more tolerable than with CPAP alone. NNV to treat severe, stable COPD remains controversial, although a subgroup of patients with hypercapnea and sleep-disordered breathing (SDB) seems most likely to respond favorably. NNV to treat central SDB in patients with congestive heart failure continues to be investigated. Recent findings from a Canadian CPAP trial were disappointing, but preliminary results on a novel adaptive NNV mode are promising.

The measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a convenient, noninvasive, point-of-service office test for airway inflammation. The first half of this practice management review presents the methodological, interpretative, and clinical applications of FeNO. The second half discusses practical management issues, including current and future technology, equipment specifications, US Food and Drug Administration regulations, cost, current procedural terminology coding, and reimbursement. The measurement of FeNO is helpful in the diagnosis of asthma. It is predictive of a response to inhaled corticosteroids (ICSs). Monitoring FeNO is useful in maintaining asthma control by allowing the assessment of adherence to medication and dose titration of ICSs. An elevated level of FeNO is predictive of asthma relapse following corticosteroid withdrawal especially in children. The advances in technology, ease of use, and clinical utility will lead to greater availability, acceptance, and routine application in the care of asthma.

Acute febrile respiratory illness (FRI) leading to respiratory failure is a common reason for admission to the ICU. Viral pneumonia constitutes a portion of these cases, and often the viral etiology goes undiagnosed. Emerging viral infectious diseases such as severe acute respiratory syndrome and avian influenza present with acute FRIs progressing to respiratory failure and ARDS. Therefore, early recognition of a viral cause of acute FRI leading to ARDS becomes important for protection of health-care workers (HCWs), lessening spread to other patients, and notification of public health officials. These patients often have longer courses of viral shedding and undergo higher-risk procedures that may potentially generate aerosols, such as intubation, bronchoscopy, bag-valve mask ventilation, noninvasive positive pressure ventilation, and medication nebulization, further illustrating the importance of early detection and isolation. A small number of viral agents lead to acute FRI, respiratory failure, and ARDS: seasonal influenza, avian influenza, coronavirus associated with severe ARDS, respiratory syncytial virus, adenovirus, varicella, human metapneumovirus, and hantavirus. A systematic approach to early isolation, testing for these agents, and public health involvement becomes important in dealing with acute FRI. Ultimately, this approach will lead to improved HCW protection, reduction of transmission to other patients, and prevention of transmission in the community.

Lung cancer causes more deaths than any other malignancy in the developed world. Advances in surgical techniques and chemotherapy/radiotherapy regimes have produced only minimal improvements in long-term survival. New therapeutic interventions are urgently required. Research has indicated that growth factor signaling may be an important novel target in lung cancer therapy. Preclinical studies have demonstrated the role of extracellular growth factors in lung cancer cell proliferation, metastasis, and resistance to cytotoxic therapy, and have elucidated the key molecular components of growth factor-signaling cascades. This has enabled the development of selective growth factor inhibitors, which have been evaluated in clinical trials and are now an accepted component of advanced lung cancer treatment. Further research is underway to improve the efficacy of this growth factor-targeted therapy. This article will outline the important aspects of this translational research indicating the growth factor-signaling pathways identified in lung cancer, clinical trials of anti-growth factor therapy, and potential future research directions.

Some studies have suggested that use of long-acting beta(2)-agonists (LABAs) leads to an increased risk for adverse events in patients with stable COPD. The purpose of this review was to assess the safety, and secondarily the efficacy of LABAs.

Toxicologic conditions are encountered in critically ill patients due to intentional or unintentional misuse of or exposure to therapeutic or illicit drugs. Additionally, toxicities related to medical interventions may develop in hospitalized patients. This review focuses on recent developments in the field of critical care toxicology. Early interventions to decrease absorption or enhance elimination of toxins have limited value. Specific interventions to manage toxicities due to analgesics, sedative-hypnotics, antidepressants, antipsychotics, cardiovascular agents, alcohols, carbon monoxide, and cholinergic agents are reviewed. Hospital-acquired toxicities due to methemoglobinemia, propylene glycol, and propofol should be recognized and treated. The clinician is continually required to incorporate clinical judgment along with available scientific data and clinical evidence to determine the best therapy for toxicologic conditions.

A large number of patients with underlying pulmonary disease travel by air each year and are therefore at risk for significant cardiopulmonary effects of induced hypoxia at higher altitudes. The hypoxia altitude simulation test provides a simple way to identify those patients at risk by simulating conditions encountered at high altitude. By asking the patient to breathe a mixture of gases with an oxygen saturation of 15.1%, the test simulates a cabin pressure of 8,000 feet and allows the physician to screen for hypoxia, significant symptoms, and arrhythmias. Repeating the test with supplemental oxygen ensure adequate treatment of those patients who have a decrease in the alveolar pressure of oxygen, significant symptoms, and/or arrhythmias.

Asthma is a chronic inflammatory disease of the airway that requires long-term antiinflammatory therapy. Inhaled corticosteroids (ICSs) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, including a long-acting beta(2)-agonist or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to increase, and additional antiinflammatory options become available, it may be possible to target antiinflammatory therapy to various aspects of the disease and consequently to improve the treatment of patients with inadequate responses to standard ICS-based therapy. Several novel antiinflammatory therapies are in different stages of clinical development. The most clinically advanced of these is omalizumab, a recombinant humanized monoclonal antibody that specifically targets IgE and is indicated for patients with moderate-to-severe asthma caused by allergies. Omalizumab has demonstrated efficacy in patients with moderate-to-severe asthma and documented evidence of allergen sensitivity. Other key therapy options in clinical development either target proinflammatory cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) or inflammatory cells (eg, T-helper type 2 cells and eosinophils). This review provides an overview of the current and future approaches targeting airway inflammation in patients with asthma.

alpha(1)-Antitrypsin deficiency (AATD) is an autosomal-codominant genetic disorder that predisposes individuals to the development of liver and lung disease. AATD is greatly underrecognized and underdiagnosed. Early identification allows preventive measures to be taken, the most important of which is the avoidance of smoking (including the inhalation of second-hand smoke) and exposure to environmental pollutants. Early detection also allows careful lung function monitoring and augmentation therapy while the patient still has preserved lung function. Cost factors and controversies have discouraged the initiation of large-scale screening programs of the newborn and adult populations in the United States and Europe (except for Sweden). There are sound medical reasons for targeted screening. Evidence-based recommendations for testing have been published by the American Thoracic Society/European Respiratory Society task force, which take potential social, psychological, and ethical adverse factors into consideration. This review discusses rationales for testing and screening for AATD in asymptomatic individuals, family members, and the general population, weighing benefits against potential psychological, social, and ethical implications of testing. For most, negative issues are outweighed by the benefits of testing. AATD testing should be routine in the management of adults with emphysema, COPD, and asthma with incompletely reversible airflow obstruction.

Beta(2)-adrenergic agonists cause a release of pulmonary surfactant into lung airways. The surfactant phospholipids maintain the patency of the conducting airways, but this function is inhibited by plasma proteins entering an inflamed airway. The physical behavior of the surfactant can be studied with a pulsating bubble surfactometer and a capillary surfactometer. Calf lung surfactant extract was found to be inhibited by plasma proteins and by a lowering of temperature. Severe breathing difficulties and malfunctioning surfactant developed in BALB/c mice inhaling ozone or infected with respiratory syncytial virus, mainly as a result of proteins invading the airways. Patients with asthma were challenged with allergens in an area of one lung. BAL fluid (BALF) from such an area contained a surfactant that functioned poorly (ie, an inability to maintain airway openness) compared with BALF from the other lung or from the lungs of healthy volunteers. When proteins in the BALF were removed, surfactant performance clearly improved. Eosinophils, so prominent in asthmatic patients, synthesize the enzyme lysophospholipase, which, together with the enzyme phospholipase A(2), catalyzes the hydrolysis of the main component of the surfactant, phosphatidylcholine. Such hydrolysis incapacitates the ability of the surfactant to maintain airway patency. The treatment of asthma with beta(2)-adrenergic agonists and steroids will have a valuable effect on the surfactant system. It will cause a release of fresh surfactant into terminal airways. Surfactant can also be nebulized and inhaled, which has been shown to be an effective treatment.

Despite many clinical examples of exemplary end-of-life care, a number of studies highlight significant shortcomings in the quality of end-of-life care that the majority of patients receive. In part, this stems from inconsistencies in training and supporting clinicians in delivering end-of-life care. This review describes the responsibilities of pulmonary and critical care physicians in providing end-of-life care to patients and their families. While many responsibilities are common to all physicians who care for patients with life-limiting illness, some issues are particularly relevant to pulmonary and critical care physicians. These issues include prognostication and decision making about goals of care, challenges and approaches to communicating with patients and their family, the role of interdisciplinary collaboration, principles and practice of withholding and withdrawing life-sustaining measures, and cultural competency in end-of-life care.

Systemic corticosteroids, antibiotics, and noninvasive positive pressure ventilation (NPPV) are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. We undertook a systematic review and metaanalysis to systematically evaluate the effectiveness of these therapies.

With increasing numbers of people traveling to high altitude for work or pleasure, there is a reasonable chance that many of these travelers have preexisting medical conditions or are receiving various medications at the time of their sojourn. As with all travelers to high altitude, they are at risk for altitude illnesses such as acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. While there are clear recommendations for pharmacologic measures to prevent or treat these illnesses, these recommendations are oriented toward healthy individuals and do not take into account the presence of preexisting medical conditions. In this review, we consider how the choice and dose of the medications used in the management of altitude illness-acetazolamide, dexamethasone, nifedipine, tadalafil, sildenafil, and salmeterol-are affected by a patient's underlying medical conditions. We discuss the indications and current dosing recommendations for individuals without underlying disease, and then consider how drug selection or dosing regimens will be affected by the presence of renal insufficiency, hepatic insufficiency, other important medical conditions, and the potential for serious drug interactions. We include comments about interactions with antimalarial medications and antibiotics used in the treatment of traveler's diarrhea, as well as the safety of use during pregnancy. By giving these issues adequate consideration, clinicians can increase the chances that properly evaluated patients with underlying medical conditions will enjoy a safe trip to high altitude.