Assessment of a bronchoscopy simulator.

The study objective was to validate a flexible bronchoscopy simulator by determining if it could differentiate between expert and novice bronchoscopists. A subsequent evaluation phase was then done to determine whether use of the simulator would improve the rate of bronchoscopy skill acquisition for new pulmonary fellows. A multicenter prospective cohort study was performed using a bronchoscopy simulator. Three cohorts were evaluated based on the number of bronchoscopies previously performed: "experts" (> 500, n = 9), "intermediates" (25 to 500, n = 8), and "novices" (none, n = 11). Each participant performed two simulated cases with performance measures being recorded by the simulator. Performance measures that distinguished between groups were then used to evaluate the learning curve for new fellows training on the simulator. A randomized-controlled trial was then conducted comparing the quality of bronchoscopy performance for new pulmonary fellows who were trained either with conventional methods or with the simulator. Expert bronchoscopists performed better on the simulator than intermediates who performed better than novices in terms of procedure time, percentage of segments visualized, time in red-out, and wall collisions. Training of new fellows demonstrated that after performing 20 bronchoscopic simulations, the skill level acquired with the simulator significantly improved in terms of speed, percentage of segments visualized, time in red-out, and collisions. Fellows trained on the simulator performed better than fellows trained using conventional methods during their first actual bronchoscopies as assessed by procedure time (815 versus 1,168 s, p = 0.001), a bronchoscopy nurse's subjective quality assessment score (7.7 +/- 0.3 versus 3.7 +/- 2.5, p = 0.05), and by a quantitative bronchoscopy quality score (percentage of segments correctly identified/procedure time, 0.119 +/- 0.015 versus 0.046 +/- 034, p = 0.03). In conclusion, the bronchoscopy simulator was able to accurately assess bronchoscopy experience level. Training new fellows on the bronchoscopy simulator leads to more rapid acquisition of bronchoscopy expertise compared with conventional training methods. This technology has the potential to facilitate bronchoscopy training and to improve objective evaluations of bronchoscopy skills.

Outpatient pleurodesis of malignant pleural effusions using a small-bore pigtail catheter.

STUDY OBJECTIVE: Patients with symptomatic malignant pleural effusion are usually treated with large-bore chest tube placement and pleurodesis requiring > or = 3 days of hospitalization. We sought to demonstrate the feasibility of ambulatory drainage and sclerosis using a small-bore pigtail catheter in patients with malignant pleural effusions. We reasoned that this approach would improve symptoms and quality of life at a reduced cost. METHODS: A 14F pigtail catheter was percutaneously inserted into the pleural space and connected to a closed gravity-drainage bag system. The patients were instructed in the use of the drainage system and discharged to return for sclerosis with 4 g of talc after the drainage was < 100 mL/24 h. Patients were graded for dyspnea and performances status using the Eastern Cooperative Oncology Group score (ECOG) and baseline and transitional dyspnea index score (BDI-TDI) before tube placement and again at 30 days. Radiographic response was graded as total response, partial response, or failure. Telephone follow-up was initiated when the patient could not return for evaluation. RESULTS: Ten ambulatory women, ages 41 to 79 years, were enrolled. The chest tube was left in place from 1 to 10 days, draining a mean of 2,956 mL (1,685 to 6,050 mL). Only two patients were unable to undergo sclerosis owing to catheter dislodgment and minimal drainage. Six reported symptomatic improvement at 30 days confirmed by TDI and ECOG scores in four of six. One with a prior history of a lobectomy was found to have a chylous pleural effusion and experienced a hydropneumothorax, for which sclerosis was unsuccessful. One died in hospital on day 26 after sclerosis despite radiographic resolution. Of the four patients who had improved dyspnea and functional status by TDI and EGOG scores, radiographic response was complete in three and partial in one. Two of the six were not able to return for follow-up because of weakness but reported improvement by telephone inquiry. CONCLUSION: Ambulatory sclerosis of malignant effusion using a small-bore catheter is a feasible alternative to inpatient sclerosis with a large-bore chest tube, especially in patients with strong preferences for outpatient care.

Differential patterns of apoptosis in resolving and nonresolving bacterial pneumonia.

Infection with either Streptococcus sanguis or Streptococcus pneumoniae type 25 causes acute pneumonitis in rats. Pneumonia caused by S. sanguis resolves over the course of 8 d, whereas pneumonia caused by S. pneumoniae type 25 progresses to fibrosis. To examine the role of apoptosis in these models, we performed assays with the terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections from rat lungs at various times, and quantified the results with image analysis. Apoptosis was a feature of both the acute and resolving stages of pneumonia. The pattern and extent of apoptosis were similar in both models during the acute stage, and the number of apoptotic nuclei increased in both models through 4 d after infection. Although there were differences in the cellular pattern of apoptosis after 2 d and 4 d of infection, the extent of apoptosis was the same in both models. After 8 d, major differences were observed. In the resolving model, apoptosis was limited primarily to an abscess in the base of the lung. In the nonresolving model, apoptosis was persistent. We also found that cyclin-dependent kinase-5 expression is upregulated during apoptosis induced by bacterial infection. These data indicate that the location and timing of apoptosis may determine whether pneumonia resolves or progresses to fibrosis.

Acute lung injury and acute respiratory distress syndrome in sepsis and septic shock.

Sepsis remains the leading cause of ARDS, and ARDS is still an often fatal condition. With our expanding knowledge of the pathobiologic mechanisms and the relationship between these two entities, early recognition, treatment, and prevention of sepsis may prevent or hasten recovery from ARDS. Understanding the biologic markers involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations to target treatment based on these mediators.

Management of acute exacerbations in chronic obstructive pulmonary disease.

An acute exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by an acute worsening of symptoms accompanied by lung infection. In severe cases, an acute exacerbation may cause respiratory failure and death. Successful management of acute exacerbation of COPD in either the inpatient or outpatient setting requires attention to a number of key issues. In this review, issues regarding the management of acute exacerbations of COPD are discussed. An inhaled beta-2 agonist along with the inhaled anticholinergic bronchodilator are recommended. Antibiotic therapy has been demonstrated to improve clinical recovery and physical outcomes. It should be directed against the most commonly occurring pathogens and, in more severe cases, coverage against Gram-negative bacteria is considered. Short course of systemic steroids does provide benefit in hospitalized patients. Supplemental oxygen is appropriate for all patients with hypoxemia. Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode. In a high number of cases, endotracheal intubation may be avoided. Promoting smoking cessation and the use of influenzae and pneumococcal vaccination may help decrease frequency of episodes of these exacerbations.

Pneumonia in the elderly: overview of diagnostic and therapeutic approaches.

Pneumonia is more frequent in the elderly and results in higher morbidity and mortality. Although the incidence of pneumonia increases with age, from 1 per 1,000 to 12 per 1,000 persons over age 75 years, comorbid medical illnesses and host defense impairments (especially heart disease, chronic obstructive pulmonary disease, and aspiration risk) are independent risk factors. The microbial etiology of pneumonia in the healthy elderly is similar to that in younger patients but shifts toward a more gram-negative and opportunistic flora with increasing age and severity of concomitant medical illness. The choice of antimicrobial therapy must be based on risk stratification (age, medical illnesses, and severity of presentation). Guidelines based on these principles will be reviewed. Pneumococcal and influenza vaccination reduce the risk of death due to pneumonia and are cost-effective preventative strategies.

Radiological manifestations of Legionella/Legionella-like organisms.

The chest radiograph of Legionellosis has been described in many reports. Although some attempted to describe patterns which are specific for Legionella, in fact, the roentgenographic findings in Legionella infection vary widely and depend largely on when in the course of illness the radiograph is obtained. Certain temporal characteristics, however, can serve to enhance the likelihood of the diagnosis of Legionella pneumonitis. Initial focal infiltrates are most commonly poorly marginated with 10% presenting with concomitant pleural effusion. The infiltrates often spread to contiguous lobes eventually becoming bilateral, with incidence of pleural effusions reaching 35%. This progression often occurs despite appropriate antimicrobial therapy and often in the face of clinical improvement. A similar pattern of progression also occurs in immunocompromised individuals; in addition, a high rate of cavitation and hilar adenopathy is seen in this subset of patients. A prolonged resolution phase of up to 6 months is common with rare development of residual densities. Correlating radiographic features with disease severity and mortality have largely been unsuccessful.

A "closed" medical intensive care unit (MICU) improves resource utilization when compared with an "open" MICU.

We hypothesized that a "closed" intensive care unit (ICU) was more efficient that an "open" one. ICU admissions were retrospectively analyzed before and after ICU closure at one hospital; prospective analysis in that ICU with an open ICU nearby was done. Illness severity was gauged by the Mortality Prediction Model (MPM0). Outcomes included mortality, ICU length of stay (LOS), hospital LOS, and mechanical ventilation (MV). There were no differences in age, MPM0, and use of MV. ICU and hospital LOS were lower when "closed" (ICU LOS: prospective 6.1 versus 12.6 d, p < 0.0001; retrospective 6.1 versus 9.3 d, p < 0.05; hospital LOS: prospective 19.2 versus 33.2 d, p < 0.008; retrospective 22.2 versus 31.2 d, p < 0.02). Days on MV were lower when "closed" (prospective 2.3 versus 8.5 d, p < 0.0005; retrospective 3.3 versus 6.4 d, p < 0.05). Pooled data revealed the following: MV predicted ICU LOS; ICU organization and MPM0 predicted days on MV; MV and ICU organization predicted hospital LOS; mortality predictors were open ICU (odds ratio [OR] 1.5, p < 0.04), MPM0 (OR 1.16 for MPM0 increase 0.1, p < 0.002), and MV (OR 2.43, p < 0.0001). We conclude that patient care is more efficient with a closed ICU, and that mortality is not adversely affected.

Lung volume reduction surgery: answering the crucial questions.

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.

Duration and route of antibiotic therapy in community-acquired pneumonia: switch and step-down therapy.

The treatment of hospitalized patients with community-acquired pneumonia (CAP) has traditional been with intravenous antibiotics. More recently, the focus of this antibiotic therapy has been empiric and based on the most likely pathogens in a given patient. The concept of when and how to approach the patient for conversion to oral therapy, known as switch therapy, is now the focus of controversy. Recently, several studies have emerged from the literature that shed some light on the subject of switch therapy for CAP. Although the data are limited at this time, it seems clear that switching to oral antibiotics in selected low-risk patients may be feasible and safe. In this article, we focus on the problem and help formulate a practical approach to switching patients from intravenous antibiotics to oral therapy for CAP.

Nuclear factor-kappaB is activated by hyperoxia but does not protect from cell death.

Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive transcription factor that is activated by oxidative insult, and NF-kappaB activation can protect cells from apoptosis. To test if NF-kappaB can protect from necrotic cell death caused by high levels of molecular O2 (hyperoxia), we exposed human alveolar epithelial (A549) cells to hyperoxia. NF-kappaB was shown to be activated and was translocated to the nucleus within minutes. Nuclear translocation persisted over the course of several days, and the levels of NF-kappaB protein and mRNA increased as well. In hyperoxia, NF-kappaB regulation was independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there was neither nuclear translocation of NF-kappaB nor any increase in expression after exposure to H2O2 at a concentration where this oxidant induces both MAPK and widespread apoptosis. Despite the activation and increased expression of NF-kappaB in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the notion that apoptosis occurs in the absence of NF-kappaB activation but indicate that protection from cell death by NF-kappaB is probably limited to apoptosis.

Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double-blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group.

OBJECTIVE: To test the effect of a novel bradykinin antagonist, deltibant (CP-0127), on survival, organ dysfunction, and other outcomes in patients with the systemic inflammatory response syndrome (SIRS) and presumed sepsis. DESIGN: Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death. SETTING: A total of 47 US referral hospitals. PATIENTS: A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems. INTERVENTIONS: Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3, 1.0, or 3.0 microg x kg(-1) x min(-1)) of deltibant. Concurrent therapy at the discretion of the treating physician. MAIN OUTCOME MEASURE: Risk-adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment was performed using a study-specific risk model derived from the APACHE III database. RESULTS: Deltibant had no significant effect on risk-adjusted 28-day survival. In a posthoc analysis, risk-adjusted 7-day survival showed a nonsignificant trend toward improvement (P=.09). The 28-day risk-adjusted survival in the prospectively defined subset of patients with gram-negative infections showed a statistically significant improvement (P=.005). CONCLUSIONS: Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.

Clostridium difficile infection as a cause of severe sepsis.

Although colitis is often seen in critically all patients who have received multiple broad-spectrum antibiotics, there are no reports describing severe sepsis as a result of Clostridium difficile infection. We describe three cases of severe sepsis with local intestinal Clostridium difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver.

Cellular oxygen toxicity. Oxidant injury without apoptosis.

All forms of aerobic life are faced with the threat of oxidation from molecular oxygen (O2) and have evolved antioxidant defenses to cope with this potential problem. However, cellular antioxidants can become overwhelmed by oxidative insults, including supraphysiologic concentrations of O2 (hyperoxia). Oxidative cell injury involves the modification of cellular macromolecules by reactive oxygen intermediates (ROI), often leading to cell death. O2 therapy, which is a widely used component of life-saving intensive care, can cause lung injury. It is generally thought that hyperoxia injures cells by virtue of the accumulation of toxic levels of ROI, including H2O2 and the superoxide anion (O2-), which are not adequately scavenged by endogenous antioxidant defenses. These oxidants are cytotoxic and have been shown to kill cells via apoptosis, or programmed cell death. If hyperoxia-induced cell death is a result of increased ROI, then O2 toxicity should kill cells via apoptosis. We studied cultured epithelial cells in 95% O2 and assayed apoptosis using a DNA-binding fluorescent dye, in situ end-labeling of DNA, and electron microscopy. Using all approaches we found that hyperoxia kills cells via necrosis, not apoptosis. In contrast, lethal concentrations of either H2O2 or O2- cause apoptosis. Paradoxically, apoptosis is a prominent event in the lungs of animals injured by breathing 100% O2. These data indicate that O2 toxicity is somewhat distinct from other forms of oxidative injury and suggest that apoptosis in vivo is not a direct effect of O2.

Severe community-acquired pneumonia.

Community-acquired pneumonia is an important public health concern and a recent focus of clinical practice guidelines. What has become clear from this renewed focus of attention is that a subgroup of patients with community-acquired pneumonia have severe disease with a differing spectrum of pathogens and prognosis. This article reviews the definition, bacteriology, diagnostic approach, and treatment of patients categorized as having severe community-acquired pneumonia. Although some of what is discussed is controversial and the literature in this area continues to expand, we focus on an evidence-based approach to this clinical problem.

Delayed resolution of pneumonia. When is slow healing too slow?

Slowly resolving or nonresolving pneumonia is a clinical challenge, but we believe it can be dealt with in a rational and decisive manner. The following risk factors have been established for delayed radiographic resolution of pneumonia and should be considered in patient evaluation: Coexisting medical conditions History of smoking, Advanced age, Multilobar involvement, Persistent fever or leukocytosis. Diabetes, chronic obstructive pulmonary disease, renal failure, and alcohol abuse can impair immune function, which slows normal clearing of infiltrates. Common and uncommon infectious agents, conditions that mimic pneumonia (eg, a neoplasm, congestive heart failure), and pulmonary complications (eg, abscess) can also result in delayed resolution.