Endogenously produced oxides of nitrogen appear to play important roles in tissue and organ homeostasis. Endogenous production of nitric oxide, which can be altered in response to various stimuli, can modulate vascular tone, oxyradical cascades, cell adhesion, and other aspects of inflammation. Because exogenously administered (inhaled) nitric oxide can mediate pulmonary vasodilatation and improve pulmonary function in some patients with lung injury, treatment of lung allograft recipients with inhaled nitric oxide may ameliorate ischemia-reperfusion injury, thereby improving perioperative pulmonary function and diminishing ventilatory support requirements. This review examines the biology of nitric oxide and present data that support its potential therapeutic effects for lung transplant recipients.

To review the clinical and laboratory findings in children with pneumococcal bacteremia during a 6-year period between 1989 and 1995.

One of the challenges in clinical cardiology is to determine the optimal time of valve replacement surgery in patients with aortic stenosis. To meet this challenge, one requires an accurate knowledge of the natural history and rate of progression of the disease. This review will summarize the natural history of aortic stenosis in terms of symptoms, mortality, and stenosis progression.

To review the pharmacology of the long-acting inhaled beta2-agonists, salmeterol and formoterol, summarize results of their clinical trials, evaluate their safety records, and discuss their roles in the treatment of asthma.

Tobacco smoking is the main cause of COPD, and encouragement and support in smoking cessation is the best way to help the patient with COPD. The three major goals of COPD management are to lessen airflow limitation, to prevent and treat secondary medical complications, and to decrease respiratory symptoms and improve quality of life. Outpatient pharmacotherapy should be organized in a stepwise manner according the severity of disease, the aims being to induce bronchodilation, reduce inflammation, and facilitate expectoration, although the role of anti-inflammatory and mucolytic treatment of COPD has not been clearly established. Patients whose conditions are not well controlled with optimal pharmacotherapy are candidates for enrollment in a pulmonary rehabilitation program. Correction or prevention of hypoxemia is a priority, and long-term oxygen therapy supplementation prolongs survival in hypoxemic patients. With only limited data on criteria for hospital admission and the objectives of hospitalization, the published standards on the management of COPD include an expert consensus statement on these aspects of hospital care. Surgery, special considerations such as sleep, nutrition, and air travel, and ethical issues are discussed.

Emphysema and other forms of COPD are not only common, but also have a poor prognosis. Mortality with severe COPD may be as high as 60% at 5 years and is associated with a significant degree of disability and cost to the health-care system. Building on Dr. Otto Brantigan's experience in the 1950s, when multiple-wedge resections of emphysematous lung were performed to decrease lung volume, thereby improving airflow and reducing hyperinflation, recent investigators, utilizing improved surgical and anesthetic technique, have redeveloped a surgical approach to the treatment of emphysema. The operations used to treat emphysema include excision of large bullae (bullectomy) and resection of diffusely emphysematous lung and are variously known as lung volume reduction surgery (LVRS), pneumectomy, and reduction pneumoplasty. These operations aim for a 20 to 30% reduction in lung volume and may be performed by stapler or laser resection, or both. The mechanisms of benefit have been attributed to enhanced elastic recoil, correction of ventilation perfusion mismatch, improved efficiency of respiratory musculature, and improved right ventricular filling. Questions that remain to be answered include duration of benefits, safety, and cost of LVRS. The National Heart, Lung, and Blood Institute and the Health Care Financing Administration have responded to the demand for more access to and information about LVRS by organizing both a national registry and controlled clinical trial of these procedures over a 7-year period. This multicenter trial intends to enroll patients with end-stage emphysema to compare methods of bilateral LVRS to maximal medical therapy.

In appropriately selected patients with COPD and alpha1-antitrypsin deficiency emphysema, lung transplantation prolongs life, improves functional capacity, and enhances quality of life. However, rejection remains an obstacle to better medium-term results, and lung transplantation is a treatment, not a cure and not a panacea.

There has been a resurgence of interest in pulmonary rehabilitation mainly because the prevalence of COPD has increased, scientific studies document consistent benefits (increased exercise endurance and reduced dyspnea), and thoracic surgeons recognize that preoperative and postoperative conditioning enhances the results of lung volume reduction surgery and lung transplantation. Although education and psychosocial/behavioral interventions are important components of a multidimensional program, exercise training of the upper and lower extremities is essential to achieve the described improvements. Current programs vary considerably in the frequency, intensity, and duration of exercise reconditioning. Two "key" questions relating to pulmonary rehabilitation are as follows. What is an appropriate training intensity? How should patients monitor the training intensity? Maintenance exercise programs and the development of home- or community-based programs will be important future developments.

Supportive therapy in COPD includes long-term oxygen therapy (LTOT) and patient support groups as two cornerstones in a comprehensive program of care known as pulmonary rehabilitation. The rich history of LTOT dating to the early 1960s and bolstered by excellent controlled clinical trials of the 1970s, along with additional advances, provided an effective therapy which improved both the quality and length of life in patients with COPD. Many patients with oxygen gain insight into coping with advanced COPD through patient support groups. The need for more cosmetically pleasing oxygen delivery systems to the nose, and future directions in providing oxygen in the home, remain challenges.

COPD is the fifth leading cause of death in the United States, and acute respiratory infections account for a significant proportion of all primary care visits. Approximately one half of all exacerbations of COPD can be attributed to bacterial infection, and antibiotic therapy has been demonstrated to improve clinical outcomes and hasten clinical and physiologic recovery. The major pathogen continues to be Haemophilus influenzae, and resistance to beta-lactam antibiotics such as ampicillin can be expected in 20 to 40% of isolated strains. Certain high-risk patients, in whom the cost of clinical treatment failure is high, can be identified by simple clinical criteria. Patients with significant cardiopulmonary comorbidity, frequent purulent exacerbations of COPD, advanced age, generalized debility, malnutrition, chronic corticosteroid administration, long duration of COPD, and severe underlying lung function tend to fail therapy with older drugs, such as ampicillin, and early relapse can be expected. Treatment directed toward resistant pathogens with potent bactericidal drugs may be expected to lead to improved clinical outcomes and overall lower costs, particularly if hospital admissions and respiratory failure can be prevented. Future studies examining the role of antibiotics should enroll these high-risk patients to determine if new therapies have significant clinical, quality-of-life, and economic advantages over older agents.

Clinical studies of acute exacerbations of COPD are difficult because of the heterogeneous nature of COPD, diffuse symptoms that can vary spontaneously, and difficulties in defining clinical response both in the short and long term. The role of bacterial infection, and thus use of antibiotics, in COPD is controversial. The available evidence shows that bacterial infection has a significant role in acute exacerbations, but its role in disease progression is less certain. Upper respiratory tract commensals, such as nontypable Haemophilus influenzae, cause most bronchial infections by exploiting deficiencies in the host defenses. Some COPD patients are chronically colonized by bacteria between exacerbations, which represents an equilibrium in which the numbers of bacteria are contained by the host defenses but not eliminated. When an exacerbation occurs, this equilibrium is upset and bacterial numbers increase, which incites an inflammatory response. Neutrophil products can further impair the mucosal defenses, favoring the bacteria, but if the infection is overcome, symptoms resolve. However, if the infection persists, chronic inflammation may cause lung damage. About half of exacerbations involve bacterial infection, but these patients are not easy to differentiate from those who are uninfected, which means that antibiotics have to be given more often than is strictly necessary. Further research is needed to characterize those patients in whom bacterial infection has a more important role.

COPD is a heterogeneous collection of conditions that can affect various structures within the lung in a number of different ways. These various processes can all result in limitation of expiratory airflow. If severe enough, this physiologic abnormality defines COPD. The various conditions that can lead to this syndrome are prevalent and often relentlessly progressive. In aggregate, they represent an important public health problem. This supplement outlines diagnostic and therapeutic strategies by which the practitioner can assist patients suffering from this condition.

To review the various methods used to diagnose lower respiratory tract infections.

During the 18th week of a first pregnancy, a 20-year-old woman visits her physician complaining of cough, sore throat, and hemoptysis of 4 days in duration. A chest radiograph, laboratory study findings including a cytoplasmic antineutrophil cytoplasmic autoantibody titer, and lung biopsy results were consistent with a limited form of Wegener's granulomatosis. She was treated successfully with prednisone and cyclophosphamide. The remainder of her pregnancy was otherwise uneventful and resulted in a normal labor and delivery of a healthy male infant.

The objective of this focused review is to describe the rationale, methods, and potential clinical applications of dobutamine stress echocardiography (DSE) in heart transplant recipients. More than 500 studies in 150 heart transplant patients who underwent this procedure (1991-96) are reviewed. Relevant studies from the medical literature that have assessed the utility of DSE in the diagnosis of transplant coronary artery disease (TCAD) are discussed, the predictive ability of DSE for development of TCAD is determined, and the prognostic value of this test in the heart transplant population is evaluated. The protocol of DSE used in the laboratory for this study is presented and discussed with reference to other major studies that have determined the sensitivity, specificity, and positive and negative predictive accuracies. Since many noninvasive cardiac tests have not been consistently optimal to detect TCAD, a substantial number of patients undergo routine surveillance with coronary angiography to define the presence and magnitude of TCAD. Recent studies with DSE have shown it to be valuable in the noninvasive diagnosis of TCAD and to have an accuracy unmatched by other widely used imaging modalities. Other important evolving indications for DSE in heart transplant patients, such as prediction of prognosis and occurrence of cardiac events, are briefly discussed. Based on this study and the currently available literature, DSE appears to be a highly reproducible noninvasive test which can be serially employed in the routine surveillance of coronary artery disease in heart transplant patients.

The history of the use of beta-blockers for congestive heart failure, beginning with the innovative seminal study by the Swedish group in 1975 to studies in 1995, is reviewed and shows that almost all trials favored the use of beta-blockers. They tended to demonstrate an increase in ejection fraction, a decrease in left ventricular mass, and in some studies, even a decrease in mortality. Even after the introduction of angiotensin-converting enzyme inhibitors, additional improvement in function and mortality was observed. Patients with nonischemic dilated cardiomyopathy derived more benefit from beta-blockers than did patients with ischemic cardiomyopathy. Least likely to benefit were patients treated for <2 months, patients with alcoholic cardiomyopathy, and those with marked intercellular fibrosis. Although the starting dose of metoprolol, the most common beta-blocker used, may have to be as low as 2.5 mg/d, mortality analysis failed to show a decrease in sudden death unless the dose was raised to about 300 mg/d, a dose at which beta-selectivity is generally not expected to be present. The non-beta-specific bucindolol or carvedilol may ultimately be preferred to metoprolol because they are better tolerated initially due to a slight vasodilatation effect. Initial studies with carvedilol showed remarkable promise in reducing mortality. However, these agents cannot yet be said to have been studied adequately.

A 69-year-old man with advanced prostate cancer was receiving antiandrogen therapy (bicalutamide [Casodex]). He developed dyspnea, peripheral eosinophilia and bilateral pulmonary interstitial infiltrates. Transbronchial biopsy confirmed pulmonary eosinophilia. Withdrawal of bicalutamide and initiation of steroid therapy resulted in clinical improvement.