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Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Cysts are commonly seen on CT scans of the lungs, and diagnosis can be challenging. Clinical and radiographic features combined with a multidisciplinary approach may help differentiate among various disease entities, allowing correct diagnosis. It is important to distinguish cysts from cavities because they each have distinct etiologies and associated clinical disorders. Conditions such as emphysema, and cystic bronchiectasis may also mimic cystic disease. A simplified classification of cysts is proposed. Cysts can occur in greater profusion in the subpleural areas, when they typically represent paraseptal emphysema, bullae, or honeycombing. Cysts that are present in the lung parenchyma but away from subpleural areas may be present without any other abnormalities on high-resolution CT scans. These are further categorized into solitary or multifocal/diffuse cysts. Solitary cysts may be incidentally discovered and may be an age related phenomenon or may be a remnant of prior trauma or infection. Multifocal/diffuse cysts can occur with lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, tracheobronchial papillomatosis, or primary and metastatic cancers. Multifocal/diffuse cysts may be associated with nodules (lymphoid interstitial pneumonia, light-chain deposition disease, amyloidosis, and Langerhans cell histiocytosis) or with ground-glass opacities (Pneumocystis jirovecii pneumonia and desquamative interstitial pneumonia). Using the results of the high-resolution CT scans as a starting point, and incorporating the patient's clinical history, physical examination, and laboratory findings, is likely to narrow the differential diagnosis of cystic lesions considerably., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Right heart thrombus in the absence of structural heart disease, atrial fibrillation, or intracardiac catheter is rare. It typically represents a thrombus migrating from the venous system to the lung, known as thrombi-in-transit, and can lead to a life-threatening pulmonary embolism. The optimal therapy for thrombi-in-transit remains controversial. We report our experience using percutaneous removal of right heart thrombus using vacuum aspiration., Methods: Patients with right atrial mass who were hemodynamically stable and underwent vacuum thombectomy using the AngioVac system (AngioDynamics) at our institution were included in this analysis. Between December 2012 and August 2014, a total of 7 patients (2 men, 5 women) with a mean age of 51.5 years (range, 20-83 years) underwent right atrial thrombectomy. Data during the procedure and follow-up period were collected and analyzed., Results: All patients were hemodynamically stable before the procedure. The procedure was considered successful in 6 patients. All patients survived through hospitalization. No periprocedural bleeding, stroke, or myocardial infarction occurred. One patient developed cardiogenic shock after the procedure that required extracorporeal membrane oxygenation support for <24 hours. There was no recurrent venous thromboembolism at a mean follow-up of 9 months., Conclusion: Vacuum-assisted thrombectomy can be a potential treatment option for hemodynamically stable patients with large right-sided intracardiac thrombus who are not surgical candidates.

Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M)-positive clones or via genetic evolution of initially EGFR(T790M)-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic.

Lung transplantation reduces mortality in patients with end-stage lung disease; however, only approximately 21% of lungs from potential donor patients undergo transplantation. A large number of donor lungs become categorized as unsuitable for lung transplantation as a result of lung injury around the time of brain death. Limiting this injury is key to increasing the number of successful lung procurements and subsequent transplants. This narrative review by a working group of pulmonologists, respiratory therapists, and lung transplant specialists elucidates principles of mechanical ventilatory support that can be used to limit lung injury in potential lung donor patients and examines the implementation of protocolized strategies in enhancing the procurement of donor lungs for transplantation.

The germinal center reaction is the process by which low-affinity B cells evolve into potent, immunoglobulin-secreting plasma and memory B cells. Since the recycling hypothesis was created, experimental studies have both tracked movement of a small population of B cells from the light zone into the dark zone, supporting the recycling model, and parallel to the light zone-dark zone interface, indicating a one-way trajectory. We present a novel, sequence-based ab initio model of protein stability and protein interactions. Our model contains a dark zone region of clonal expansion and somatic hypermutation and a light zone site of antigenic selection. We show not only that a one-shot model is sufficient to achieve biologically-realistic rates of affinity growth, population dynamics, and silent:non-silent mutation ratios in the complementary determining region and framework region of antibodies, but also that a stochastic recycling program with or without realistic constraints on the structural stabilities of GC antibodies cannot produce biologically-observed affinity growth, population dynamics or silent:non-silent mutation profiles. The effect of recycling erases affinity gains made by potent antibodies cycling back from the light zone and causes B cells to pool in the dark zone under high replication rates.

In this second part of a two-part series, we describe an algorithmic approach to the diagnosis of the solitary pulmonary nodule (SPN). An essential aspect of the evaluation of SPN is determining the pretest probability of malignancy, taking into account the significant medical history and social habits of the individual patient, as well as morphologic characteristics of the nodule. Because pretest probability plays an important role in determining the next step in the evaluation, we describe various methods the physician may use to make this determination. Subsequently, we outline a simple yet comprehensive algorithm for diagnosing a SPN, with distinct pathways for the solid and subsolid SPN.

The solitary pulmonary nodule (SPN) is frequently encountered on chest imaging and poses an important diagnostic challenge to clinicians. The differential diagnosis is broad, ranging from benign granulomata and infectious processes to malignancy. Important concepts in the evaluation of SPNs include the definition, morphologic characteristics via appropriate imaging modalities, and the calculation of pretest probability of malignancy. Morphologic differentiation of SPN into solid or subsolid types is important in the choice of follow-up and further management. In this first part of a two-part series, we describe the morphologic characteristics and various imaging modalities available to further characterize SPN. In Part 2, we will describe the determination of pretest probability of malignancy and an algorithmic approach to the diagnosis of SPN.

Plain chest roentgenogram remains the most commonly ordered screening test for pulmonary disorders. Its lower sensitivity demands greater accuracy in interpretation. This greater accuracy can be achieved by adhering to an optimal and organized approach to interpretation. It is important for clinicians not to misread an abnormal chest radiograph (CXR) as normal. Clinicians can only acquire the confidence in making this determination if they read hundreds of normal CXRs. An individual should follow the same systematic approach to reading CXRs each time. All clinicians must make a concerted effort to read plain CXRs themselves first without reading the radiologist report and then discuss the findings with their radiology colleagues. Looking at the lateral CXR may shed light on 15% of the lung that is hidden from view on the posteroanterior film. Comparing prior films with the recent films is mandatory, when available, to confirm and/or extend differential diagnosis. This article outlines one of the many systematic approaches to interpreting CXRs and highlights the lesions that are commonly missed. A brief description of the limitations of CXR is also included.

Bronchiolar disorders are generally difficult to diagnose because most patients present with nonspecific respiratory symptoms of variable duration and severity. A detailed clinical history may point toward a specific diagnosis. Pertinent clinical questions include history of smoking, collagen vascular disease, inhalational injury, medication usage, and organ transplant. It is important also to evaluate possible systemic and pulmonary signs of infection, evidence of air trapping, and high-pitched expiratory wheezing, which may suggest small airways involvement. In this context, pulmonary function tests and plain chest radiographs may demonstrate abnormalities; however, they rarely prove sufficiently specific to obviate bronchoscopic or surgical biopsy. Given these limitations, in our experience, high-resolution CT (HRCT) scanning of the chest often proves to be the most important diagnostic tool to guide diagnosis in these difficult cases, because different subtypes of bronchiolar disorders may present with characteristic image findings. Three distinct HRCT patterns in particular are of value in assisting differential diagnosis. A tree-in-bud pattern of well-defined nodules is seen primarily as a result of infectious processes. Ill-defined centrilobular ground-glass nodules point toward respiratory bronchiolitis when localized in upper lobes in smokers or subacute hypersensitivity pneumonitis when more diffuse. Finally, a pattern of mosaic attenuation, especially when seen on expiratory images, is consistent with air-trapping characteristic of bronchiolitis obliterans or constrictive bronchiolitis. Based on an appreciation of the critical role played by HRCT scanning, this article provides clinicians with a practical algorithmic approach to the diagnosis of bronchiolar disorders.

Objective: The purpose of this article is to describe 3 patients each of whom developed a different form of tracheobronchial aspergillosis., Methods: We describe our clinical experience with 3 patients who developed significant respiratory symptoms secondary to Aspergillus infection. All patients were followed closely until there was resolution of pulmonary problems or they succumbed to respiratory insufficiency., Results: The first patient had asthma and her clinical and bronchoscopic findings were compatible with the diagnosis of mucoid impaction syndrome caused by Aspergillus. Response to therapy was excellent with complete recovery. The second and third patients had what we believe was tracheobronchial pseudomembranous aspergillosis. The precise reason for this complication in the second patient is unknown. The third patient was immunosuppressed and developed tracheobronchial aspergillosis. Despite aggressive therapy, both of these patients died. Diagnostic bronchoscopy was helpful in detecting the airway abnormalities and for obtaining respiratory specimens for culture., Conclusions: These cases show the diverse tracheobronchial manifestations of Aspergillus species. Diagnostic bronchoscopy was helpful in the diagnosis of airway involvement by aspergillus.

During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial (Nu/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

In a patient with acute respiratory illness (cough, sputum production, chest pain, and/or dyspnea), the need for chest imaging depends on the severity of illness, age of the patient, clinical history, physical and laboratory findings, and other risk factors. Chest radiographs seem warranted when one or more of the following are present: age > or = 40; dementia; a positive physical examination; hemoptysis; associated abnormalities (leukocytosis, hypoxemia); or other risk factors, including coronary artery disease, congestive heart failure, or drug-induced acute respiratory failure. Chest CT may be warranted in complicated cases of severe pneumonia and in febrile neutropenic patients with normal or nonspecific chest radiographic findings. Literature on the indications and usefulness of radiologic studies for acute respiratory illness in different clinical settings is reviewed.

Macrophages undergo fusion to form multinucleated giant cells in several pathologic conditions, including the foreign body response (FBR). We detected high levels of matrix metalloproteinase (MMP)-9 during macrophage fusion in vitro and in foreign body giant cells (FBGCs) in vivo. Wild-type (WT) bone marrow-derived macrophages were induced to fuse with IL-4 in the presence of MMP-9 function-blocking antibodies and displayed reduced fusion. A similar defect, characterized by delayed shape change and abnormal morphology, was observed in MMP-9 null macrophages. Analysis of the FBR in MMP-9 null mice was then pursued to evaluate the significance of these findings. Specifically, mixed cellulose ester disks and polyvinyl alcohol sponges were implanted s.c. in MMP-9 null and WT mice and excised 2-4 weeks later. Histochemical and immunohistochemical analyses indicated equal macrophage recruitment between MMP-9 null and WT mice, but FBGC formation was compromised in the former. In addition, MMP-9 null mice displayed abnormalities in extracellular matrix assembly and angiogenesis. Consistent with a requirement for MMP-9 in fusion, we also observed reduced MMP-9 levels in MCP-1 null macrophages, previously shown to be defective in FBGC formation. Collectively, our studies show abnormalities in MMP-9 null mice during the FBR and suggest a role for MMP-9 in macrophage fusion.

The present investigation was aimed at providing the pharmacological basis for the medicinal use of a polyherbal formulation (POL-10) in hypertension and dyslipidemia. In spontaneously hypertensive rats, POL-10 significantly (p<0.05) reduced blood pressure to 183.2+/-2.97 vs 198.1+/-5.2 mmHg (Mean+/-S.E.M; n=7-10), improved endothelial dysfunction (p<0.01) by increasing acetylcholine-induced relaxation up to 46.0+/-6.7% vs 24.6+/-3.8% (n=5-10) and decreased serum triglycerides (TG) to 54.5+/-3.3 vs. 93.84+/-5.7 mg/dl (p<0.001). In high fat diet-induced hypercholesterolemia, POL-10 caused reduction in total cholesterol (TC), low density lipoproteins (LDL) levels and the atherogic index (TC-HDL/HDL). It decreased TG levels in tyloxapol-induced hyperlipidemia and increased high-density lipoprotein cholesterol (HDL-C) and reduced atherogenic index in normotensive rats. It exhibited strong antioxidant activity in different in vitro assays. In isolated smooth muscle preparation, POL-10 exhibited calcium channel blocking (CCB) activity by inhibition of high K(+)- induced contractions and rightward shift of Ca(++) concentration-response curves similar to that of verapamil. In conclusion, these findings rationalize the medicinal use of POL-10 in cardiovascular disorders which are mediated through multiple pathways such as, antioxidant, CCB, inhibition of lipid biosynthesis and absorption.

Background: A determination of serum Transthyretin (TTR, Prealbumin) level is an objective method of assessing protein catabolic loss of severely ill patients and numerous studies have shown that TTR levels correlate with patient outcomes of non-critically ill patients. We evaluated whether TTR level correlates with the prevalence of PEM in the ICU and evaluated serum TTR level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients., Methods: We studied PEM prevalence in 118 patients admitted to a community hospital's medical intensive care unit and the association between TTR, low albumin (ALB) concentration and high-risk disease (HRD), i.e., sepsis, inability to take in oral nutrients, etc. Serum TTR was measured on the day of admission, day 3 and day 7 of their ICU stay. APACHE II and SOFA score was assessed on the day of admission and the nutritional status and nutritional requirement was assessed for their entire ICU stay. Patients were divided into three groups based on initial TTR level and the outcome analysis was performed for APACHE II score, SOFA score, ICU length of stay, hospital length of stay, and mortality., Results: TTR showed excellent concordance with patients classified with PEM or at high malnutrition risk, and followed for 7 days, it is a measure of the metabolic burden. TTR levels decline from day 1 to day 7 in spite of providing nutritional support. Patients were classified in 3 categories with respect to the level of TTR: more than 170 mg/L, twenty-five patients (group 3); 100-170 mg/L, forty-eight patients (group 2); less than 100 mg/L, forty-five patients (group 1). TTR level correlated with ICU length of stay, hospital length of stay, and APACHE II score, and predicts mortality., Conclusions: TTR identified patients at highest risk for metabolic losses associated with stress hypermetabolism as serum TTR levels did not respond early to nutrition support because of the delayed return to anabolic status. It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition.

IV heroin use is associated with several well-described complications, including noncardiogenic pulmonary edema, aspiration pneumonitis, ARDS, pneumonia, lung abscess, septic pulmonary emboli, and atelectasis. Foreign-body granulomatosis may develop when drug users inject solutions containing crushed oral tablets in which talc is used as filler and can be complicated by pulmonary fibrosis. The effects are distinct from pulmonary edema, which may occur acutely with heroin injection. We describe the case of a young female patient who was an IV heroin user who also smoked cigarettes, and presented with progressive dyspnea, hypoxia, and bilateral lung infiltrates. The final pathologic diagnosis in this case was one that had not been previously reported in IV heroin users.

Background: New information is available on pleural diseases. The authors selected articles to make recommendations on diagnostic and treatment aspects of pleural diseases., Materials and Methods: Eleven articles published in the English language between 2004 and 2007 were chosen. The basis of selection of the articles was the impact on daily practice, change in prior thinking of a disease process or specific treatment modality, as well as proper design and execution of the study. 5-Amino-laevulinic acid with fluorescent light combined with white light may allow further diagnostic yield in undiagnosed pleural disease. FDG-PET may allow prognostication of patients with pleural tumors. Utilizing ultrasound by trained Emergency Department physicians is a rapid and effective technique to evaluate non-traumatic pleural effusions in symptomatic patients. Serum osteopontin levels may distinguish patients exposed to asbestos with benign disease from those with pleural mesothelioma. Administration of streptokinase in patients with empyema does not need for surgical drainage, length of hospital stay, or mortality as compared to conventional treatment with chest tube drainage and intravenous antibiotics. Silver nitrate may be an alternative agent to talc for producing pleurodesis. Routine use of graded talc (50% particles greater than 25 microns) is recommended to reduce the morbidity associated with talc pleurodesis. Study design does not permit us to conclude that aspiration of spontaneous pneumothorax is as effective as chest tube drainage. Pleural catheter may prove to be an important palliative modality in treating debilitated patients or patients with trapped lung who show symptomatic improvement with drainage; however, at the present time, these catheters cannot be considered a first line treatment option for patients with malignant pleural effusion. One of the studies reviewed showed no significant difference in tract metastasis in patients with malignant mesothelioma undergoing an invasive pleural procedure with or without irradiation to the procedure site. However, the design of the trial does not allow us to make this conclusion at the present time.

The evaluation of patients presenting with multinodular pulmonary disease provides an important clinical challenge for physicians. The differential diagnosis includes an extensive list of benign and malignant processes making the management of these cases frequently problematic. With the introduction of high-resolution CT (HRCT) scanning, the ability to assess various patterns of diffuse multinodular disease has evolved into an essential part of the diagnostic process. The purpose of this article is to develop an approach to the diagnosis of multinodular parenchymal disease using HRCT scan pattern recognition as a point of departure.

Amniotic fluid embolism is a rare syndrome that can have debilitating and lethal consequences. It is a difficult and somewhat intangible diagnosis that warrants a high index of suspicion by physicians. Prompt and aggressive supportive treatment is required to lessen an otherwise dismal outcome, which may include death and permanent disability. This article provides an account of the protean clinical features, pathogenesis, and principles involved in treatment.

Background: Thiopurine drugs (azathioprine and 6-mercaptopurine) are well established in the treatment of patients with inflammatory bowel disease. However, some patients are intolerant or resistant to thiopurine drugs and their management remains a challenge. Several studies have suggested methotrexate is effective for the induction and maintenance of remission in Crohn's disease., Objective: This study was conducted because the overall data on clinical efficacy of methotrexate in inflammatory bowel disease remain limited and there are no data regarding fistulating Crohn's disease or concomitant use of methotrexate with thiopurine drugs in inflammatory bowel disease., Methods: This study was a retrospective review of medical notes. Clinical response was defined as sustained withdrawal of oral steroids or fistula improvement. New episodes of steroid therapy, infliximab or surgery during the first 6 months were considered as failure to achieve clinical response., Results: Seventy-two patients were studied (66 Crohn's disease and six ulcerative colitis). The mean dose of methotrexate used was 18.2 mg/week. Clinical response was achieved in 22 of 54 patients (40.7%) who completed 6 months of methotrexate treatment. For patients with Crohn's disease, fistula improvement was achieved in eight of 18 (44.4%) patients compared with 11 of 30 (36.7%) receiving methotrexate for steroid withdrawal. Clinical response was achieved in six of 15 patients (40%) treated with methotrexate and azathioprine at the same time compared with 16 of 39 patients (41%) treated with methotrexate alone., Conclusions: Methotrexate is reasonably effective in clinical practice as a steroid sparing agent in inflammatory bowel disease. The efficacy in fistulating Crohn's disease justifies its use as an immunomodulator in these patients. Combined azathioprine and methotrexate treatment appears to offer no advantage over methotrexate alone.

Purpose of Review: Computed tomography scans are commonly used in imaging lung diseases. As more information accumulates, patterns of rare or new diseases on CT scans are being increasingly reported. Several pulmonary diseases have distinguishing features, which are better delineated on high resolution CT scans than plain chest radiographs. The radiographic features of unusual diffuse lung diseases published in the past two years are described., Recent Findings: Severe acute respiratory syndrome generally manifests as focal or diffuse bilateral areas of consolidation on chest radiography and reticulation with ground-glass attenuation commonly seen on CT scans. A normal HRCT rules out the diagnosis of Pneumocystis carinii pneumonia while a normal chest radiograph does not. Immunocompromised patients without AIDS, who have CMV pneumonia, generally demonstrate a combination of ground-glass attenuation, air-space consolidation, and small nodules on HRCT. Nodules less than 10 mm in size in immunocompromised patients are highly suggestive of viral infections. Bronchial wall thickening on HRCT associated with cavitating nodules is suggestive of Wegner granulomatosis in the appropriate clinical setting. Small cysts may be seen in a minority of patients with subacute hypersensitivity pneumonitis and centrilobular emphysema in chronic farmer's lung. Reversed halo sign has a high specificity for cryptogenic organizing pneumonia. The triad of ground-glass opacities, ill-defined centrilobular nodules and cysts and focal areas of air trapping is highly suggestive of subacute hypersensitivity pneumonitis., Summary: Familiarizing with radiographic and CT scan patterns may help the clinician to exclude certain diagnoses and narrow the differential diagnosis for others.

Rheumatologic emergencies may pose a serious threat to life, and the treatment of patients with these illnesses continues to be challenging. In the last decade extensive animal and human research has led to development of new therapies. Considerable progress has been made in the therapy for RA. Newly developed biologic therapies have shown promising results in clinical studies, and two agents have already been approved by the FDA. These drugs are currently available for therapy and are under close postmarketing scrutiny to assess long-term efficacy and safety. Similar therapies are under investigation for SLE. Plasmapheresis, once used for many diseases, is now restricted mostly to conditions for which its use has been shown to be beneficial in randomized, controlled studies. Immunoadsorption is used to target specific disease-producing pathogens for removal during extracorporeal therapy. Evidence is accumulating for the use of IVIGs in several immune-mediated conditions. The outlook for some emergencies continues be grim, however, and various therapies are used based on evidence from anecdotal case reports and case series. The new therapies are relatively safe, but careful monitoring is needed, because there is potential for serious adverse events.

Since the development of the flexible bronchoscope in late 1960s, its use in the management of various pulmonary disorders, especially lung Ca, has expanded tremendously. It is not only of great diagnostic value, with the recent development of various therapeutic modalities such as Nd:YAG laser, tracheobronchial stents, and cryotherapy, but also its value in management of terminal lung Ca has improved dramatically. Its potential in curing early-stage lung Ca presently is being explored. At present, it is at least partially successful in achieving this goal. More importantly, because of lack of the training in RB and widespread usage of FB, it is more likely that its role in the various interventional procedures, such as Nd:YAG laser therapy, tracheobronchial stent deployment, brachytherapy, and cryotherapy, will grow exponentially. Because of availability of a variety of therapeutic modalities, such as APC, PDT, and balloons, interventional pulmonologists are well equipped to improve the quality of life of terminally ill patients with cancer and maybe to cure early stage lung Ca.

This article gives a broad overview of the increasingly important applications of bronchoscopy, flexible (FOB) and rigid (RB), in a modern medical intensive care unit. Special emphasis is made to bronchoscopy use in mechanically ventilated patients. Therapies such as endobronchial stenting and Nd:YAG laser are being used to improve respiratory failure and facilitate weaning from mechanical ventilation. Practical applications of recent advancements in technology (endobronchial stenting, laser therapy, and so forth), the increasing use of rigid bronchoscopy, and the new generation of flexible bronchoscopes like battery bronchoscopes, and ultra-thin bronchoscopes, are also discussed. The risks, potential benefits, complications, and suggested technique of performing bronchoscopy in mechanically ventilated patients are reviewed.

Background: Some critically ill patients have difficulty in mobilizing their respiratory secretions. These patients can develop pulmonary atelectasis that may result in hypoxemia. There are some data to show that atelectasis may be prevented by turning a patient from side to side utilizing special beds., Study Objectives: To determine the role of kinetic therapy (KT) combined with mechanical percussion (P) in the resolution of established atelectasis of the lungs and hypoxemia in critically ill, hospitalized patients. (KT was defined as rotation of a patient along the longitudinal axis of > or = 40 degrees to each side continuously.), Design: Prospective and randomized study (2:1 test to control group)., Patients: Twenty-four patients with respiratory failure, either mechanically ventilated or spontaneously breathing, who demonstrated segmental, lobar, or unilateral entire lung atelectasis were studied., Setting: Medical ICU and adult respiratory ward in a county hospital in New York., Interventions: Seventeen patients were treated with KT combined with mechanical P using a KT system (Triadyne Kinetic Therapy System; KCI; San Antonio, TX). Seven patients received manual repositioning and manual P every 2 h. Both groups received similar conventional therapy with inhaled bronchodilators and suctioning., Results: Partial or complete resolution of atelectasis was seen in 14 of 17 patients (82.3%) in the test group as compared with 1 of 7 patient (14.3%) in the control group. The median duration to resolution of atelectasis was 4 days in the test group. Bronchoscopy was performed in 3 of 7 patients in the control group, but in none of the patients in the test group. A cost of $720 was incurred per patient for utilizing the specialty beds for a mean duration of 4 days. An improvement in oxygenation index occurred in the test group (change in baseline PaO2/fraction of inspired oxygen from 207.4+/-106.7 mm Hg to 318+/-100.7 mm Hg) at the end of therapy, while the control group showed a reduction over a similar duration of time (181.3+/-96.3 mm Hg to 112+/-21.2 mm Hg)., Conclusions: KT and mechanical P therapy resulted in significantly greater partial or complete resolution of atelectasis as compared with conventional therapy. There was a generalized trend toward statistical significance in the improvement of oxygenation and a reduced need for bronchoscopy in the group receiving KT and P therapy.

The differential diagnosis of pulmonary disorders in the HIV-infected individual is broad. Clinical features and chest radiographs may point towards a diagnosis but cannot reliably establish one. It is important to know the conditions in which bronchoscopy, BAL, and TBB are likely to be diagnostic, just as it is to know when other invasive or noninvasive procedures may be more useful. Finally, the incidence of transmission of infections such as tuberculosis during bronchoscopy and cross-contamination of patients with an improperly sterilized bronchoscope, cannot be overemphasized.

During a clinical trial of orally administered ciprofloxacin in respiratory tract infections, changes in serum theophylline levels were evaluated in 33 hospitalized patients who also required theophylline therapy. Patients received intravenous theophylline in standard titrated doses and 750 mg of oral ciprofloxacin twice daily. Serum theophylline levels in all patients were measured before and during ciprofloxacin therapy. The mean serum pretreatment theophylline level was 7.8 +/- 4.6 micrograms/ml; during ciprofloxacin therapy, the level increased to 14.6 +/- 7.4 micrograms/ml. Twenty of the 33 (61 percent) patients evaluated had increases in serum theophylline levels by a mean value of 10.5 micrograms/ml. In 30 percent of patients who experienced increases, theophylline concentrations were in the toxic range. This occurred more frequently in elderly patients with chronic obstructive pulmonary disease. In light of the frequency and potential severity of this interaction, careful monitoring of serum theophylline levels in patients receiving theophylline and ciprofloxacin is recommended.

The efficacy and safety of ciprofloxacin in bacterial bronchitis were compared with those of ampicillin in a double-blind, prospective clinical trial. Eighty-seven patients received either oral ciprofloxacin (750 mg twice daily) or oral ampicillin (500 mg four times daily). Ciprofloxacin was as effective as ampicillin and produced a 98 percent clinical cure rate. Significantly more pretreatment bacterial isolates were susceptible to ciprofloxacin (p less than 0.05), and ciprofloxacin had a significantly higher rate of sputum sterilization than did ampicillin (p less than 0.05). Ciprofloxacin showed broad in vitro antibacterial activity with particularly low minimal inhibitory concentrations for gram-negative organisms. Ciprofloxacin was well tolerated; there were few adverse effects, and patients had a significantly lower incidence of diarrhea with ciprofloxacin than with ampicillin (p less than 0.05). Ciprofloxacin was an effective and well-tolerated treatment for bacterial bronchitis that had the advantages of broad in vitro antibacterial activity and twice-daily dosing.

The efficacy and safety of ciprofloxacin in an oral dose of 750 mg twice daily, in the treatment of respiratory infections was studied in 129 patients. Ciprofloxacin showed broad in-vitro antibacterial activity and was highly effective in both Gram-negative and Gram-positive infections with a clinical cure rate of 96%. The major side effect was an interaction with theophylline particularly in the elderly patients.