The mystery of diastolic heart failure (DHF), described by authorities as a "puzzle" and a "clinical paradox," stems from the following misperception: (1) that the normal ejection fraction implies normal cardiac output (CO), (2) that therefore low CO is not operative (it is rarely mentioned in relation to the pathophysiology of DHF), and (3) the congestive phenomena are due to the stiff left ventricle. In fact, a normal ejection fraction is not a reliable indicator of normal CO; low CO is the fundamental pathophysiologic abnormality of all heart failure (HF), whether systolic and/or diastolic (or, indeed, "high output"); and increased ventricular stiffness is not the principal cause of congestion in DHF. Pathophysiologic explorations supporting these understandings further reveal the following: (1) the premise that a clinical event as dramatic as acute pulmonary edema (systolic and/or diastolic) would be contingent on similarly dramatic acute hypertensive or ischemic ventricular dysfunction, while intuitive, is unsubstantiated, and there is an alternate explanation satisfying both theoretical and clinical observations; (2) contrary to general perception, DHF is no more vulnerable to diuretic-induced hypotension than systolic HF; (3) heart rate reduction should not yet be considered an established therapeutic goal in DHF; (4) since HF is HF whether systolic and/or diastolic, studies are likely to show that therapeutic similarities outweigh differences except as the various agents might modify the underlying structural and/or functional pathology; (5) although long evident that HF occurs by only two mechanisms (systolic dysfunction and/or diastolic dysfunction), it has only recently been acknowledged that the mere exclusion of one is diagnostic of the other; and (6) the definition of HF currently in widespread use is unnecessarily confounded by neglect of the fundamental distinction between ventricular dysfunction and failure.

The treatment of descending thoracic aortic aneurysms using endovascular stents is one of the more recent advances in treatment and is receiving increasing attention as it is a less invasive alternative to open surgical repair. Although the technology is still primitive, significant improvements have lately been made in the design and deployment of the endovascular stent-grafts. Aortic stent-grafts were used initially to exclude abdominal, and later thoracic, aortic true and false aneurysms. These prostheses have been increasingly used to treat aneurysms, dissections, and traumatic ruptures of the descending thoracic aorta with good early and mid-term outcomes. Although the long-term outcome of patients with aneurysms of the descending thoracic aorta after stent graft implantation has not been investigated, continued refinement of the endovascular approaches has decreased the need for conventional open thoracic aortic aneurysm repair, especially in patients who are at a high risk for standard surgery because of advanced age or the presence of comorbid diseases. The placement of endoluminal stent-grafts to exclude the dissected or ruptured site of thoracic aortic aneurysms is a technically feasible and relatively safe procedure. With the rapid development of endovascular approaches, the treatment of the descending thoracic aortic aneurysms might alter even more, but an extended follow-up is necessary to determine the longer term outcome. Historical perspectives, advantages, device considerations, complications, and current perspectives of the endovascular stent grafting of the descending thoracic aortic aneurysms are elaborated on.

Noninvasive positive-pressure ventilation (NPPV) has been used increasingly to treat acute respiratory failure (ARF). The best indications for its use are ARF in patients with COPD exacerbations, acute pulmonary edema, and immunocompromised states. For these indications, multiple controlled trials have demonstrated that therapy with NPPV avoids intubation and, in the case of COPD and immunocompromised patients, reduces mortality as well. NPPV is used to treat patients with numerous other forms of ARF, but the evidence is not as strong for its use in those cases, and patients must be selected carefully. The best candidates for NPPV are able to protect their airway, are cooperative, and are otherwise medically stable. Success is optimized when a skilled team applies a well-fitted, comfortable interface. Ventilator settings should be adjusted to reduce respiratory distress while avoiding excessive discomfort, patient-ventilator synchrony should be optimized, and adequate oxygenation should be assured. The appropriate application of NPPV in the acute care setting should lead to improved patient outcomes and more efficient resource utilization.

Fiberoptic bronchoscopy has become a commonplace procedure in ICUs. Despite the fact that one of the most common indications for bronchoscopy is the presence of retained secretions and atelectasis, there is little research dedicated to its safety and utility in this clinical situation. This article presents a case of an intubated trauma victim who had undergone numerous bronchoscopic procedures, with varying degrees of success, for retained secretions and atelectasis. This review then seeks to answer the following three main questions regarding bronchoscopy in critically ill patients: (1) Is bronchoscopy effective in resolving atelectasis? (2) Is bronchoscopy superior to other means of resolving atelectasis? (3) Is bronchoscopy safe in critically ill patients? The patient was a 28-year-old man with no significant medical history who presented to the emergency department after his car was hit by a dump truck. He was found to have multiple leg fractures and a splenic rupture, and he was taken to the operating room for an exploratory laparotomy, splenectomy, and reduction of his fractures. He was then brought to the surgical ICU intubated, sedated, and receiving mechanical ventilation. Over the next 6 h, he developed progressive hypoxemia and diffuse, bilateral alveolar infiltrates on a chest radiograph (CXR). Four days postoperatively, a routine CXR revealed total atelectasis of his right upper lobe (RUL). Emergent bronchoscopy was performed, and a large mucus plug obscuring the RUL bronchus was removed. Follow-up CXR demonstrated resolution of the atelectasis. The next day, RUL atelectasis was again seen on his CXR. A repeat bronchoscopic examination and BAL failed to reveal any plug. A follow-up CXR showed continued atelectasis. Over the next week, the patient underwent daily bronchoscopy for atelectasis with variable degrees of improvement. Over the next 3 weeks, his pulmonary status improved until he was eventually extubated, and 1 month after hospital admission he was discharged to rehabilitation.

The potential benefits of noninvasive positive pressure ventilation (NIPPV) for patients with COPD remains inconclusive, as most studies have included only a small number of patients. We therefore undertook a meta-analysis of randomized controlled trials (RCTs) that compared nocturnal NIPPV with conventional management in patients with COPD and stable respiratory failure.

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in the elderly, and the leading cause of death among residents of nursing homes. Oropharyngeal aspiration is an important etiologic factor leading to pneumonia in the elderly. The incidence of cerebrovascular and degenerative neurologic diseases increase with aging, and these disorders are associated with dysphagia and an impaired cough reflex with the increased likelihood of oropharyngeal aspiration. Elderly patients with clinical signs suggestive of dysphagia and/or who have CAP should be referred for a swallow evaluation. Patients with dysphagia require a multidisciplinary approach to swallowing management. This may include swallow therapy, dietary modification, aggressive oral care, and consideration for treatment with an angiotensin-converting enzyme inhibitor.

Cystic fibrosis (CF) is associated with mutation and abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) that affects cellular chloride transport. Clinically, CF of the lung is associated with excessive accumulation of secretions, including the sulfated glycosaminoglycans, chondroitin sulfate and dermatan sulfate (DS), both of which contain sulfated N-acetylgalactosamine residues. The sulfatase enzymes, which are a highly conserved group of enzymes with high specificity for designated sulfate groups, include arylsulfatase B, a lysosomal enzyme. Arylsulfatase B, also known as N-acetyl galactosamine 4-sulfatase, can degrade DS and chondroitin-4 sulfate. Previously reported data demonstrated diminished activity of arylsulfatase B in lymphoid cell lines of patients with CF compared to normal control subjects. Frequent infections with Pseudomonas, a sulfatase-producing organism, occur in patients with CF, whereas infections with Mycobacterium tuberculosis, which lacks sulfatase activity, are infrequent. Additional investigation to determine if diminished function of arylsulfatase B is a consistent finding in cells of patients with CF may be informative, and may help to correlate the molecular, biochemical, and clinical characteristics of CF.

This review discusses the scientific and clinical evidence for cardiac rehabilitation in patients who have undergone percutaneous revascularization, heart transplant, and heart valve surgery, and in patients with chronic heart failure. Across these diagnoses, regardless of age, there is considerable benefit of cardiac rehabilitation and supervised exercise training for increasing functional capacity, favorably modifying disease-related risk factors, decreasing symptoms, detecting signs and symptoms of disease before they become serious complications, and improving quality of life. The available evidence for this component of cardiovascular disease management, albeit not perfect, still warrants its more widespread application.

Lung cancer continues to be the leading case of cancer deaths in the United States. In patients with resectable non-small cell lung cancer, surgical resection is the treatment of choice. An accurate preoperative general and pulmonary-specific evaluation is essential as postoperative complications and morbidity of lung resection surgery are significant. After confirming anatomic resectability, patients must undergo a thorough evaluation to determine their ability to withstand the surgery and the loss of the resected lung. The measurement of spirometric indexes (ie, FEV(1)) and diffusing capacity of the lung for carbon monoxide (DLCO) should be performed first. If FEV(1) and DLCO are > 60% of predicted, patients are at low risk for complications and can undergo pulmonary resection, including pneumonectomy, without further testing. However, if FEV(1) and DLCO are < 60% of predicted, further evaluation by means of a quantitative lung scan is required. If lung scan reveals a predicted postoperative (ppo) values for FEV(1) and DLCO of > 40%, the patient can undergo lung resection. If the ppo FEV(1) and ppo DLCO are < 40%, exercise testing is necessary. If this reveals a maximal oxygen uptake (O(2)max) of > 15 mL/kg, surgery can be undertaken. If the O(2)max is < 15 mL/kg, surgery is not an option. This review discusses the existing modalities for preoperative evaluation prior to lung resection surgery.

Dependence on tobacco, like many other drug dependencies, is a complex behavior with both genetic and environmental factors contributing to the variance. The heritability estimates for smoking in twin studies have ranged from 46 to 84%, indicating a substantial genetic component to smoking. Candidate gene studies have detected functional polymorphisms in genes coding for the cytochrome P450 enzymes, and variations in these genes that lead to more rapid nicotine metabolism have been implicated in smoking. Similarly, smoking has been associated with polymorphisms in dopaminergic genes that may influence the dopamine receptor number and/or function. Animal experiments have localized specific subunits of the nicotinic receptors that may mediate the reinforcing properties of nicotine and have investigated their role in nicotine dependence. However, environmental factors have also been found to contribute to the risk of initiation and persistence of smoking. We review the scientific evidence that supports a role for genetic influences on smoking, discuss the specific genetic and neurobiological mechanisms that may mediate susceptibility to nicotine dependence, identify possible gene/environmental interactions that may be important in understanding smoking behavior, and suggest directions for future research. Insights into the genetic contributions to smoking can potentially lead to more effective strategies to reduce smoking.

Non-small cell lung cancer (NSCLC) in the United States will continue to be a major public health issue, particularly as our elderly population grows. As surgery offers the best hope of cure for NSCLC, staging of NSCLC is critical because it directly impacts on the management of lung cancer. Cost, quality of life, safety, and accuracy of various staging methods all influence the clinical outcome. Staging of NSCLC is evolving due to the emergence of new and improved technologies. The objective of this article is to review the current methods used in staging of NSCLC. Currently, positron emission tomography and endoscopic ultrasound (EUS) show promise in identifying patients that may benefit from surgery. Histologic confirmation via EUS-guided fine-needle aspiration, however, may still be necessary to accurately stage the mediastinum.

To summarize the available data on COPD prevalence and assess reasons for conflicting prevalence estimates in the published literature.

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon disorder of adult smokers associated with a significant morbidity. Arising from the aberrant accumulation of Langerhans and other immune cells, PLCH tends to cause a relatively isolated pulmonary involvement as compared to other forms of Langerhans cell (LC) and histiocytic disorders. Increased knowledge of cytokine triggers, dendritic cell trafficking, and clonality of LC populations in PLCH have resulted in an improved understanding of the pathobiology of PLCH. High-resolution CT (HRCT) of the chest has led to better appreciation of nodular and cystic radiographic abnormalities characteristic of the disease. Correlation of HRCT abnormalities with lung pathologic changes has led to an improved comprehension of clinical evolution of PLCH. Current clinical predictors for PLCH outcomes remain poor, although long-term follow-up and radiologic monitoring may help to define disease progression. This review discusses advances in PLCH emphasizing the etiopathologic bases of the disease and currently available radiologic modalities for monitoring disease progression.

Acute upper viral respiratory infection (VRI) is the number one cause of illness for which patients seek medical care in the United States. Rhinoviruses, members of the family Picornaviridae, are the causative pathogens in more than half of VRIs, and they are associated with acute exacerbations of respiratory disease, including asthma, sinusitis, otitis media, and COPD. Owing to the lack of commercial availability of rapid and cost-effective laboratory tests to confirm the presence of VRI, the diagnosis is most commonly made empirically, based on patient history and physical examination. Currently, no antiviral agents that are active against picornaviruses are available for clinical use. Antimicrobial agents, frequently prescribed for VRIs, are not active against viruses, and their inappropriate and widespread use has contributed to an increase in antimicrobial resistance among bacteria commonly involved in respiratory tract infections. Several newer antiviral agents are being evaluated for treatment of VRIs. Although a variety of mechanisms and agents have been tested, few have shown significant clinical benefit in human trials. The most advanced antiviral agent in clinical trials is pleconaril, a novel viral capsid-binding inhibitor with potent and highly specific in vitro activity against the majority of serotypes of rhinoviruses and enteroviruses. Clinical trials of pleconaril for the treatment of VRIs have been conducted, and the role of pleconaril in patients with chronic lung disease is being evaluated.

Nosocomial acquisition of microorganisms resistant to multiple antibiotics represents a threat to patient safety. Here we review the mechanisms that have allowed highly resistant strains belonging to the Enterococcus genus to proliferate within our health-care institutions. These mechanisms indicate that decreasing the prevalence of resistant organisms requires active surveillance, adherence to vigorous isolation, hand hygiene and environmental decontamination measures, and effective antibiotic stewardship. We suggest how to tailor such a complex, multidisciplinary program to the needs of a particular health-care setting so as to maximize cost-effectiveness.

The use of corticosteroids as adjunctive therapy for severe sepsis and septic shock has been a source of controversy for the past 35 years. Despite a wealth of preclinical data supporting both survival and physiologic benefit for early steroid use, the data in human sepsis have been much less convincing. There have even been reports suggesting the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Recent trials have reported hemodynamic and survival benefits associated with the use of more physiologic steroid replacement therapy in patients with vasopressor-dependent septic shock. These results coupled with the observation of "relative adrenal insufficiency" in some patients with severe sepsis and septic shock may once again establish a defined role for corticosteroid therapy in the management of severe sepsis and septic shock.