The prescribing of antibiotics in the ICU is usually empiric, given the critical nature of the conditions of patients hospitalized there. Appropriate antibiotic utilization in this setting is crucial not only in ensuring an optimal outcome, but in curtailing the emergence of resistance and containing costs. We propose that research in the ICUs is vitally important in guiding antibiotic prescription practices and, therefore, the achievement of above-stated goals. There is wide institutional diversity in the relative prevalence of predominant pathogens and their antimicrobial susceptibilities, and within individual ICUs there exist unique patient populations with varying risks for and susceptibilities to infections and specific pathogens. Appropriate antibiotic prescription practices should be formulated based on surveillance studies and research at individual ICUs; these goals can be accomplished utilizing existing resources.

Nuclear factor-kappa B (NF-kappaB) is a family of DNA-binding protein factors that are required for transcription of most proinflammatory molecules, including adhesion molecules, enzymes, cytokines, and chemokines. NF-kappaB activation seems to be a key early event in a variety of cell and animal model systems developed to elucidate the pathobiology of lung diseases. The purpose of this short review is to describe what is known about the molecular biology of NF-kappaB and to review information that implicates NF-kappaB in the pathogenesis of lung disease, including ARDS, systemic inflammatory response syndrome, asthma, respiratory viral infections, occupational and environmental lung disease, and cystic fibrosis.

Tuberculosis (TB) has been and continues to be one of the most significant pathogens in terms of human morbidity and mortality. Although the resurgence of TB has been held in check in most developed countries, the epidemic rages on in most developing countries of the world. The specter of drug resistance is becoming a more credible challenge in many parts of the world, dimming the prospects of eventual elimination. However, great opportunities are arising as well, with an unprecedented focus on the global aspects of TB control. This article will review the status of TB today and put into perspective the prospects for its elimination in the coming century.

Chemical pleurodesis is an effective treatment for malignant pleural effusion and pneumothorax. This mode of therapy is, however, less widely accepted in the treatment of patients with refractory benign or undiagnosed pleural effusion.

Research on smoking has increased in the past several years, and many new therapeutic modalities have been developed. Primary intervention for smoking cessation begins with systematic identification of smokers and a formal diagnosis of nicotine dependence. Providing self-help brochures without clinical advice has marginal efficacy, but these can be useful as an adjunct to clinician intervention. Several large studies have shown that physician advice alone can lead to quit rates of up to 10%, and follow-up for patients trying to quit can double cessation rates. Behavioral therapy alone has demonstrated cessation rates of approximately 20% for those willing to participate. Drug therapy remains the most attractive method of smoking cessation for many patients. The standard approach has been nicotine substitution using one of the four forms of nicotine replacement (gum, patches, nasal spray, inhaler) currently available. The efficacy of nicotine replacement products is similar, with each agent providing a doubling of the cessation rate. Thus, the choice of agent depends on patient factors and preference. Bupropion is the first nonnicotine-containing agent approved for smoking cessation, with cessation rates ranging from 10.5 to 24.4%, depending on dose. One-year follow-up suggests a continued benefit with this agent. The combination of bupropion and transdermal nicotine has also been shown to be effective for smoking cessation in clinical trials. Effective approaches to smoking cessation should combine identification of smokers, provision of advice at each visit, and widespread availability of treatment.

The current understanding of the biology and molecular biology of lung cancer pathogenesis and progression is reviewed. Awareness of the influence of growth factors, oncogenes, and tumor suppressor genes as well as signal transduction and angiogenesis pathways on the natural history of cancer cells has led to attempts to develop new therapeutic strategies directed at interrupting tumor cell growth. Treatments utilizing monoclonal antibodies, matrix metalloproteinase inhibitors, and gene transfer and alteration are currently being investigated. The rationale and effectiveness of these treatments in early trials are explored, and recommendations for future directions in cell biology research are presented. Interest in the biology and molecular biology of tumor cells has led to some important findings that may provide opportunities for new treatments. Several of these new directions for anticancer therapy are already being examined in phase I clinical trials.

Approximately 45,000 new cases of small cell lung cancer (SCLC) will be diagnosed in the United States this year. Combination chemotherapy is the cornerstone of treatment for all stages of this disease and results in high response rates (65 to 85%), leading to a meaningful survival advantage for these patients. Patients with limited-stage disease enjoy a median survival of 10 to 15 months with chemotherapy, as compared to 3 months without drug therapy. With addition of chest radiotherapy, survival is further prolonged to 12 to 20 months. Patients with extensive-stage disease experience an average survival of 1.5 months without chemotherapy and 7 to 11 months with chemotherapy. However, no further improvement in survival has been demonstrated since combination chemotherapy regimens were introduced in the late 1970s and early 1980s, despite evaluating numerous strategies; the 5-year survival for all patients remains dismal at 5%. Clearly, new chemotherapy agents with novel mechanisms of action are needed.

Paclitaxel, the first of the taxanes, has exhibited unique and encouraging single-agent activity in the treatment of non-small cell lung cancer (NSCLC). Yet, with single-agent response rates approaching 25%, it was logical to examine the impact of paclitaxel in combination chemotherapy regimens. In trials evaluating the activity of paclitaxel in combination with one of the platinum compounds, cisplatin or carboplatin, response rates have ranged from 35 to > 50% and were significantly better than response rates observed with etoposide/cisplatin, the previous standard regimen for treatment of NSCLC. Docetaxel is a newer taxane that also has exhibited notable single-agent activity and response rates ranging from 20 to 50% when combined with cisplatin. Future research will look to refine the use of taxane combinations in NSCLC and to examine the potential of these unique and promising drugs when combined with newer agents that are active against this disease.

Strides have been made in the treatment of lung cancer in the last decade that warrant a more optimistic outlook toward the disease. The recent development of several new agents with single-agent activity, including paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan, is important, and those agents offer even greater potential when they are used in combination chemotherapy regimens or in combined-modality programs. The experience to date with therapy results with these agents in the treatment of lung cancer is reviewed and is compared to results documented with the current standard treatments for lung cancer, namely, cisplatin and cisplatin-based combination regimens. Published and ongoing trials are outlined, and directions for future research and the future goals of lung cancer therapy are outlined. The availability of newer chemotherapeutic agents that are active in lung cancer has led to response rates as high as 40% in the treatment of non-small cell lung cancer. These drugs have been shown to be active in combination drug regimens as well as when combined with radiotherapy. Future research will focus on using these agents in two- and three-drug regimens as radiation sensitizers and in combination programs with new drugs and biological agents with apparent activity against this disease.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in most industrialized nations, including the United States. Frequently, patients with unresectable disease are treated with symptomatic care alone or, in the case of locally advanced, unresectable lesions, with radiotherapy alone. In general, chemotherapy is viewed as ineffective, and therefore rarely recommended except by medical oncologists. Over the past 2 decades, however, it has become clear that chemotherapy, and in particular cisplatin-based chemotherapy, provides a modest survival advantage. In addition, recent studies indicate that chemotherapy can improve tumor-related symptoms and quality of life. With modern chemotherapy, median survival averages around 9 to 10 months in advanced NSCLC, a figure comparable to that achieved with treatment of extensive-stage small cell lung cancer, a malignancy generally viewed as chemotherapy sensitive. Importantly, existing data indicate that chemotherapy is also cost-effective. Given these observations, it is appropriate today for patients with advanced NSCLC to receive chemotherapy.

Over the last decade, we have witnessed improved outcome among patients with non-small cell lung cancer (NSCLC), principally through the use of new and novel treatment programs. A meta-analysis of randomized clinical trials comparing combined chemotherapy and radiation to radiation therapy alone clearly has shown a survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with thoracic radiation therapy over radiation therapy alone. In addition, combining thoracic radiation therapy with novel drugs or new drug combinations has yielded improvements in median survival duration and long-term survival rates in locally advanced unresectable NSCLC. Paclitaxel and carboplatin are two novel agents that have undergone extensive clinical evaluation at various doses and schedules in combination with thoracic radiation therapy in patients with locally advanced disease. There remains a need, however, for further improvement in metastatic control and prevention of locoregional recurrences. This will likely be achieved through the optimization of chemotherapy regimens to be used in combined modality therapy with thoracic radiation therapy.