Pleural Drainage Strategy After IPC Placement: A Focused Clinical Review.

The first indwelling pleural catheter (IPC) received Federal Drug Administration approval in 1997, nearly 40 years after John Chambers first described instillation of talc into the pleural space for palliation of malignant pleural effusions. Since then IPCs have revolutionized the management of malignant pleural effusions, providing an effective means of controlling dyspnea in the end stages of life without the pain and prolonged hospital stays long associated with chemical sclerosing agents. While palliation of symptoms is the primary purpose of IPCs, development of pleurodesis in the outpatient setting is often an important secondary goal. Historically, decisions regarding IPC drainage frequency have been largely arbitrary and only recently has the evidence started to emerge regarding the effects of specific drainage strategies on both symptom control and pleurodesis development. This focused clinical review explores the current literature regarding IPC drainage strategies as well as novel methods designed to improve the efficacy of IPCs in a thorough and systematic manner. In addition, this review provides an in-depth analysis and synthesis of the data focusing on key considerations needed to develop patient-centered and cost-effective strategies for the use of IPCs in malignancy.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

BACKGROUND: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. METHODS: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. RESULTS: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. CONCLUSION: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

Flexible Bronchoscopy.

Flexible bronchoscopy has changed the course of pulmonary medicine. As technology advances, the role of the flexible bronchoscope for both diagnostic and therapeutic indications is continually expanding. This article reviews the historical development of the flexible bronchoscopy, fundamental uses of the flexible bronchoscope as a tool to examine the central airways and obtain diagnostic tissue, and the indications, complications, and contraindications to flexible bronchoscopy.

Biochemical studies of membrane bound Plasmodium falciparum mitochondrial L-malate:quinone oxidoreductase, a potential drug target.

Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc1 complex inhibitor.

Evaluation of Appropriate Mediastinal Staging among Endobronchial Ultrasound Bronchoscopists.

RATIONALE: Endobronchial ultrasound (EBUS) has transformed mediastinal staging in lung cancer. A systematic approach, beginning with lymph nodes contralateral to the primary tumor (N3), is considered superior to selective sampling of radiographically abnormal nodes. However, the extent to which this recommendation is followed in practice remains unknown. OBJECTIVES: To assess the frequency with which pulmonologists, pulmonary fellows, and interventional pulmonologists endoscopically stage lung cancer appropriately. METHODS: Bronchoscopists currently performing EBUS were surveyed about their practice patterns, procedural volume, and self-confidence in EBUS skills; they then performed a proctored simulated staging EBUS. The primary outcome was the proportion of participants who appropriately initiated ultrasonographic evaluation with the N3 nodal stations in a simulated patient undergoing EBUS for mediastinal staging. RESULTS: Sixty physicians (22 interventional pulmonologists, 18 general pulmonologists, and 20 pulmonary fellows) participated in the study. The rates of appropriate staging by study group were 95.5% (21 of 22) for interventional pulmonologists, 44.4% (8 of 18) for general pulmonologists, and 30.0% (6 of 20) for pulmonary fellows (P < 0.001). Increased procedural volume correlated with appropriate staging practices (P < 0.001). Within each group, we assessed the concordance between self-confidence in EBUS and simulation performance. Among interventional pulmonologists, the concordance was 95.4%, followed by 61.1% for general pulmonologists and 40.0% for pulmonary fellows. CONCLUSIONS: General pulmonologists and pulmonary fellows were less likely than interventional pulmonologists to perform appropriate EBUS staging. In addition, the lack of concordance between self-confidence and appropriate staging performance among noninterventionists signals a need for improved dissemination of guidelines for EBUS-guided mediastinal staging.

Interventional pulmonology for asthma and emphysema: bronchial thermoplasty and bronchoscopic lung volume reduction.

Emphysema and asthma are responsible for economic and social burden. Altering the natural course of these diseases is a field of intense research. The National Emphysema Treatment Trial showed that lung volume reduction surgery (LVRS) could significantly reduce both morbidity and mortality in properly selected patients. LVRS is seldom performed, however, due to the high morbidity associated with the surgery. Numerous bronchoscopic interventions have been introduced with the goal of providing the clinical benefits of LVRS without the surgical complications. Thus far, these modalities have not produced the results once hoped. However, through active modification of both technique and patient selection, the role of minimally invasive modalities in the treatment of emphysema continues to evolve. Bronchial thermoplasty (BT) is a method of delivering controlled heat to airway mucosa with the goal of reducing airway smooth muscle mass and hence bronchoconstriction. In patients suffering from asthma who cannot achieve control with standard medical care, BT has been shown to be safe and improves symptoms, with long lasting benefit. BT does not seem to affect traditional markers of asthma severity such as forced expiratory volume in 1 second and questions remain regarding proper patient selection for this therapy and its true physiologic effects. This article is a review of bronchoscopic modalities for emphysema and asthma.