Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the ICU. Patients who acquire VAP have higher mortality rates and longer ICU and hospital stays. Because there are other potential causes of fever, leukocytosis, and pulmonary infiltrates, clinical diagnostic criteria are overly sensitive in the diagnosis of VAP. Employing quantitative cultures of bronchopulmonary secretions in the diagnostic algorithm leads to less antibiotic use and probably to lower mortality. With respect to microbiologic diagnosis, it is not clear that the use of a particular sampling method (bronchoscopic or nonbronchoscopic), when quantitatively cultured, is associated with better outcomes. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Hence, the focus of initial antibiotic therapy should be to rapidly provide antibiotic coverage for all likely pathogens and to then narrow or focus the antibiotic spectrum based on the results of quantitative cultures. Eight days of antibiotic therapy appears equivalent to 15 days of therapy except when treating nonlactose-fermenting Gram-negative organisms. In this latter situation, longer treatment durations appear to reduce the risk of recrudescence after discontinuation of antibiotic therapy. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for multidrug-resistant organisms.

Perioperative myocardial infarction (PMI) is a major cause of morbidity and mortality in patients undergoing noncardiac surgery. The incidence of PMI varies depending on the method used for diagnosis and is likely to increase as the population ages. Studies have examined different methods for prevention of myocardial infarction (MI), including the use of perioperative beta-blockers, alpha(2)-agonists, and statin therapy. However, few studies have focused on the treatment of PMI. Current therapy for acute MI generally involves anticoagulation and antiplatelet therapy, raising the potential for surgical site hemorrhage in this population. This article reviews the possible mechanisms, diagnosis, and treatment options for MI in the surgical setting. We also suggest algorithms for treatment.

Proteomics is the study of the entire protein complement of the genome (the proteome) in a biological system. Proteomic studies require a multidisciplinary approach and have only been practical with the convergence of technical and methodologic improvements including the following: advances in mass spectrometry and genomic sequencing that now permit the identification and relative quantization of small amounts (femtomole) of nearly any single protein; new methods in gel electrophoresis that allow the detection of subtle changes in protein expression, including posttranslational modifications; automation and miniaturization that permit high-throughput analysis of clinical samples; and new bioinformatics and computational methods that facilitate analysis and interpretation of the abundant data that are generated by proteomics experiments. This convergence makes proteomics studies practical for pulmonary researchers using BAL fluid, lung tissue, blood, and exhaled breath condensates, and will facilitate the research of complex, multifactorial lung diseases such as acute lung injury and COPD. This review describes how proteomics experiments are conducted and interpreted, their limitations, and how proteomics has been used in clinical pulmonary medicine.

The role of thrombotic arteriopathy in the pathophysiology of idiopathic pulmonary arterial hypertension (IPAH) and the use of anticoagulants in the treatment of IPAH are currently controversial issues. This article reviews the evidence for a role of vascular thrombosis in the pathophysiology of IPAH. There is sufficient biological rationale to support the notion that thrombotic arteriopathy is an important pathophysiologic feature of pulmonary arterial hypertension (PAH) and that its progression materially contributes to disease progression. To date, the data from observational studies suggest that anticoagulation with warfarin is an effective intervention in patients with IPAH. Its efficacy in other causes of PAH remains speculative.

Despite numerous published reports, there is no consensus in the literature as to whether the surgical repair of the pectus excavatum improves cardiovascular function. As a result, it has been suggested that correction should be considered a cosmetic procedure, and therefore, many health insurance companies have questioned whether the repair of the pectus excavatum improves cardiovascular function and thus are reluctant to authorize the procedure. The purpose of this study was to apply metaanalysis methodology to generate a quantitative synthesis of the effects of surgical repair on cardiovascular function and to test the hypothesis that surgical repair of the pectus excavatum results in significant improvements in cardiovascular function.

Sleep/wake complaints, and specifically insomnia, are some of the more common problems encountered in the outpatient setting. Despite its prevalence, few clinicians are experts at diagnosing and treating this entity. Additionally, diagnosis and treatment of insomnia is a time-intensive process (often the initial interview takes at least 1 h, depending on the complexity of the insomnia). With a conservative estimate of the annual cost of insomnia between dollar 92.5 and dollar 107.5 billion dollars, it is becoming clear that insomnia has significant medical and public health implications. A problem that has hampered insomnia research is the lack of a standard definition of insomnia for use in research, as well as guidelines for assessment. In recent years, there have been important advances in the classification, evaluation, and treatment of insomnia with efforts to establish greater consensus in how to define and measure insomnia. Cognitive behavioral and pharmacologic therapies have been shown to be effective treatment approaches. Insomnia is a complex entity, often multifactorial in its etiology; and as research and clinical guidelines are established and validated (leading to better data interpretation), continued enhancement of our understanding of this disorder is expected.

Multidrug-resistant tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis that is resistant to both isoniazid and rifampicin with or without resistance to other drugs, is a phenomenon that is threatening to destabilize global tuberculosis (TB) control. MDR-TB is a worldwide problem, being present virtually in all countries that were surveyed. According to current World Health Organization and the International Union Against Tuberculosis and Lung Disease estimates, the median prevalence of MDR-TB has been 1.1% in newly diagnosed patients. The proportion, however, is considerably higher (median prevalence, 7%) in patients who have previously received anti-TB treatment. While host genetic factors may contribute to the development of MDR-TB, incomplete and inadequate treatment is the most important factor leading to its development, suggesting that it is often a man made tragedy. Efficiently run TB control programs based on a policy of directly observed treatment, short course (DOTS), are essential for preventing the emergence of MDR-TB. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services for mycobacterial cultures and in vitro sensitivity testing as it the requires prolonged use of costly second-line drugs with a significant potential for toxicity. The judicious use of drugs; supervised standardized treatment; focused clinical, radiologic, and bacteriologic follow-up; and surgery at the appropriate juncture are key factors in the successful management of these patients. With newer effective anti-TB drugs still a distant dream, innovative approaches such as DOTS-Plus are showing promise for the management of patients with MDR-TB under program conditions and appear to be a hope for future.

Ventilator-associated pneumonia (VAP), a major cause of ICU infection, results in high morbidity, mortality, and health-care costs. Multiple risk factors for VAP involve complex host factors and ubiquitous pathogens that require several different types of prevention strategies. Prevention efforts should focus on reducing bacterial colonization, and limiting aspiration, antibiotic exposure, and use of invasive devices. Although evidence-based prevention guidelines are available, they are lengthy, often ignored, and not implemented. New insights into the barriers to implementation of effective prevention programs are emerging. This article provides highlights from recent guidelines and publications discussing VAP prevention strategies and examines barriers to their implementation. Prevention and implementation of cost-effective strategies to reduce risk and improve patient outcomes should be prioritized. Clearly, prevention programs should be population specific and may vary among hospitals, but a multidisciplinary prevention team led by a "champion" is recommended to help set priorities, benchmarking goals, analyze data, and sow the seeds of change for risk reduction.

T helper (Th) type 2 cytokines, particularly interleukin (IL)-4, IL-5, and IL-13, may be important in the development of allergic asthma. Humanized monoclonal antibodies (MoAbs) against IL-5 and a recombinant human soluble IL-4 receptor (sIL-4R) have been developed as possible treatments. These approaches have not yet proven to be successful in patients with persistent asthma. This may suggest that neither IL-4 nor IL-5 is important in asthma pathogenesis. There is, however, insufficient information about the efficacy of sIL-4R and the anti-IL-5 MoAbs in asthma to draw any firm conclusions about the importance of these Th2 cytokines. Also, the administration of the potentially antiinflammatory cytokines IL-12 and interferon-gamma has not shown benefit in asthmatic patients. By contrast, the treatment of severe oral steroid-dependent asthma with soluble tumor necrosis factor-alpha receptor has demonstrated very promising results, suggesting that this cytokine plays an important role in the persistence of severe asthma.

Patient-focused or patient-centered care is not a new concept, but its value has been overlooked in preference to the technology-based, disease-centered model that has prevailed in medicine for the last 50 years. Patient-focused care includes four broad areas of intervention: communication with patients, partnerships, health promotion, and physical care (medications and treatments). We can conceptualize patient-focused care as being the care we would like our loved ones to receive. There is considerable evidence that patients prefer a patient-focused approach. Unfortunately, there are also many studies detailing physicians' disconnection with patients' needs, particularly the need for information, and misunderstandings and assumptions based on poor communication. However, it is possible to develop physicians' skills in patient-focused care and provide physicians with the tools to overcome the barriers to this approach. The patient-focused approach has been shown to improve physicians' performance, patient satisfaction, and health outcomes without requiring additional investment in time or resources. Patient-focused care has also been shown to improve adherence to medication/advice, a well-known problem in asthma. There are also benefits to the physician in terms of improved outcomes for their patients, higher patient retention, and potentially a reduced risk of litigation. Patient-focused care may be a particularly valuable approach for the management of "difficult-to-treat" patients. In summary, the "three Cs" of patient-focused care-communication, continuity of care, and concordance (finding common ground)-are highly relevant to the effective treatment of pulmonary disease and should be a key component of asthma management.

Good-quality outcomes in asthma hinge not just on the availability of medications but also on their appropriate use by patients: optimal "self-management." In asthma, low rates of adherence to prophylactic (preventer) medication are associated with higher rates of hospitalization and death. Many patients choose not to take their medication because they perceive it to be unnecessary or because they are concerned about potential adverse effects. Approximately one third of asthma patients have strong concerns about adverse effects from inhaled corticosteroids (ICS). These concerns are not just related to the experience of local symptoms attributed to ICS side effects, but also include more abstract concerns about the future, arising from the belief that regular use of ICS will result in adverse long-term effects or dependence. We need more effective ways of eliciting and addressing patients' concerns about ICS. The development of ICS options with an improved safety profile remains a key objective. However, the ideal solution is not just pharmacologic. We also need more effective ways of communicating the relative benefits and risks to patients in order to facilitate informed adherence. Clinicians must be prepared to work in an ongoing partnership with patients to ensure that they are offered a clear rationale as to why ICS are necessary and to address their concerns about potential adverse effects. This approach, based on a detailed examination of patients' perspectives on asthma and its treatment, and an open, nonjudgmental manner on the part of the clinician, is consistent with the idea of concordance.

Inhaled corticosteroids (ICS) are considered the most effective asthma therapy, but concerns remain about side effects. The ideal ICS would have a larger therapeutic ratio than currently available agents, allowing doses to be increased but without greatly increasing the frequency or severity of adverse events. The ideal ICS would possess the following pharmacokinetic properties to maximize efficacy and minimize side effects: high pulmonary deposition, conversion to an active metabolite, high receptor potency, high pulmonary retention, low oral bioavailability, extensive metabolism, and rapid elimination. The new ICS ciclesonide has been shown to possess many of these characteristics. Ciclesonide has also been shown to improve lung function, to treat the underlying inflammation, to be effective as monotherapy in patients with persistent asthma, to have reduced side effects compared with other ICS, and to be easy to use with once-daily dosing. However, as with all new products, the advantages witnessed in clinical trials still have to be demonstrated to be beneficial long-term in general clinical use. ICS with an improved therapeutic index may have the potential to increase patient adherence, enhance the use of ICS monotherapy in the primary care setting, and increase the range of patients for whom ICS monotherapy would be appropriate.

The National Asthma Education and Prevention Program 1997 guidelines and 2002 update provide an overview of potential local and systemic side effects associated with inhaled corticosteroids (ICS) and suggest ways of minimizing the risk of these side effects occurring. Despite the guidelines and extensive clinical experience of the safe use of ICS, a significant number of physicians retain concerns regarding side effects. Local side effects may lead to patients discontinuing therapy, with or without the knowledge of their physicians. In particular, concerns regarding systemic side effects, such as growth retardation in children and osteoporosis, remain relatively widespread. Pharmacokinetic studies reveal that different ICS compounds and formulations result in different degrees of systemic bioavailability, indicating possible differences in their potential to cause systemic side effects. However, clinical studies that can be used to differentiate between ICS formulations are generally lacking. Consequently, there is a need to continue to further our understanding of side effects with ICS, with the aim of identifying formulations, devices, and doses with an optimal risk/benefit ratio. The introduction of new agents with potentially improved safety profiles may reassure physicians and patients as to the relative benefits of ICS therapy in asthma.

Asthma is underdiagnosed and undertreated or inappropriately treated, even though approximately 300 million people worldwide currently have the disease. While asthma in most patients can be controlled using currently available medications, in practice this rarely happens. Despite the wide availability of treatment guidelines, there are clear discrepancies between recommendations and the reality of treatment. There is excessive use of relief medications, particularly among patients with moderate-to-severe persistent asthma, coupled with a marked underuse of inhaled corticosteroids (ICS). This underuse by patients is likely to be related to anxiety about side effects and a misunderstanding about asthma. Many patients overestimate their degree of control and have a perceived lack of need for medication. Early therapeutic intervention, with optimal antiinflammatory therapy and a stepwise approach, has a positive impact on long-term outcomes, achieving suppression of airway inflammation, prompt symptom control, and restoration of pulmonary function. Even at low doses, ICS rapidly improve clinical symptoms and measures of lung function, while their long-term use markedly reduces the frequency and severity of exacerbations and asthma mortality. Although ICS monotherapy achieves successful control of persistent asthma in a significant proportion of patients, add-on therapy with a long-acting beta2-agonist provides control for most patients with moderate-to-severe persistent asthma. Fixed combination inhalers (ICS plus a long-acting beta2-agonist) have become popular, but these have drawbacks and there is the potential for overuse. In conclusion, ICS are the cornerstone of therapy for persistent asthma of all degrees of severity in adults and children, and early therapeutic intervention is recommended for optimal long-term outcome.

Asthma is a chronic inflammatory disease involving many different cell types and cellular elements. Evidence suggests that, in the long term, this inflammation leads to remodeling of the airways, airflow obstruction, and the bronchial hyperreactivity symptoms of asthma, and is present even in patients with intermittent disease. Patients with allergic asthma and those with seasonal allergic rhinitis are believed to have minimal persistent inflammation, and the two diseases often occur together. Early intervention with inhaled corticosteroids (ICS) is believed to modify the disease process and may limit long-term remodeling. ICS remain the cornerstone and "gold standard" of treatment for asthma.

The most widely known method of asthma classification is the severity classification recommended in the National Asthma Education and Prevention Program 1997 guidelines, which also formed the basis of the Global Initiative for Asthma guidelines. This method was developed to direct a hierarchy of asthma therapy based on the patient's severity of disease. However, this severity classification has not been validated and has a number of limitations; in particular, it is challenging for physicians to apply reliably. Moreover, it does not allow asthma control to be assessed after the initiation of treatment, even though symptom control is a key objective of the treatment guidelines. A number of tools have been evaluated to provide longitudinal information on asthma control, and some of these have been validated. Clinically relevant measures of inflammation, such as eosinophilic airway inflammation, may also be helpful in classifying asthma and in guiding the use of antiinflammatory therapy. This may be a particularly useful approach in patients who are asymptomatic but have poor lung function, by permitting physicians to determine whether inflammatory processes are active, thus requiring ICS therapy. In the clinical setting, easy-to-use tools are needed to enable longitudinal assessments of symptom control and (ideally) disease progression.

There has been a sharp increase in the global prevalence, morbidity, mortality, and economic burden associated with asthma over the last 40 years, particularly in children. Approximately 300 million people worldwide currently have asthma, and its prevalence increases by 50% every decade. In North America, 10% of the population have asthma. Asthma is underdiagnosed and undertreated, although the use of inhaled corticosteroids has made a positive impact on outcomes. The increasing number of hospital admissions for asthma, which are most pronounced in young children, reflect an increase in severe asthma, poor disease management, and poverty. Worldwide, approximately 180,000 deaths annually are attributable to asthma, although overall mortality rates have fallen since the 1980s. Most asthma deaths occur in those > or = 45 years old and are largely preventable, frequently being related to inadequate long-term medical care or delays in obtaining medical help during the last attack. The financial burden on patients with asthma in different Western countries ranges from $300 to $1,300 per patient per year, disproportionately affecting those with the most severe disease. There are a number of significant barriers to reducing the burden of asthma, particularly in developing countries, where many patients have limited access to care and essential medications. The Global Initiative for Asthma has outlined a six-point patient management plan to address the effective handling of the increased number of patients in primary care. The plan focuses on patient education, written treatment plans, and ongoing communication and review with patients and their providers.

Pleural effusions are an extremely common problem affecting approximately 1.5 million people in the United States each year. Over the last several years, the use of portable ultrasound machines has greatly enhanced the evaluation and management of patients with pleural disease. This article will review the relevant literature supporting the use of ultrasound for the evaluation of patients with pleural disease and address some practical practice management issues regarding ultrasonography.

COPD is projected to be the third-leading cause of death by the year 2020. Pharmacotherapy for COPD is palliative at best, having no impact on slowing the progression of the disease. The introduction of newer therapies such as long-acting forms of bronchodilator and anticholinergic agents, together with the inclusion of inhaled corticosteroids (ICSs) in the recent Global Initiative for COPD therapeutic algorithm, have expanded the pharmacotherapy options for the treatment of COPD. This article provides a methodologic critique of the available pharmacoeconomic evidence on drug therapy for stable COPD in an effort to complement treatment guidelines and to identify any need for future pharmacoeconomic research. Relevant search strategies revealed a total of 28 economic evaluations of which 7 satisfied the study inclusion criteria. The Drummond 10-point checklist was used for the methodological critique of the economic evaluations. Five of seven pharmacoeconomic studies were conducted alongside a randomized controlled trial, and six of seven were cost-effectiveness analyses. Of the bronchodilators, the long-acting anticholinergic agent tiotropium is considered to be cost-effective relative to ipratropium. No conclusive information could be reached for the cost-effectiveness of long-acting beta-agonists. A Markov analysis showed ICSs to be cost-effective for patients with moderate-to-severe COPD relative to standard care. However, assumptions of the model may bias this conclusion, and additional studies are warranted, especially compared to other treatments. The authors suggest that additional pharmacoeconomic studies be conducted to assess the cost-effectiveness of long-acting beta-agonists and ICSs, between classes of bronchodilators, and between various combination therapies.

Apoptosis and the removal of apoptotic cells (termed efferocytosis) are tightly coupled with the regulation of normal lung structure, both in the developing and adult organism. Processes that disrupt or uncouple this balance have the potential to alter normal cell turnover, ultimately resulting in the induction of lung pathology and disease. Apoptotic cells are increased in several chronic inflammatory lung diseases, including cystic fibrosis (CF), non-CF bronchiectasis, COPD, and asthma. While this may well be due to the enhanced induction of apoptosis, increasing data suggest that the clearance of dying cells is also impaired. Because efferocytosis appears to be a key regulatory checkpoint for the innate immune system, the adaptive immune system, and cell proliferation, the failure of this highly conserved process may contribute to disease pathogenesis by impeding both the resolution of inflammation and the maintenance of alveolar integrity. The recognition of impaired efferocytosis as a contributor to chronic inflammation may ultimately direct us toward the identification of new disease biomarkers, as well as novel therapeutic approaches.