Endobronchial valves in the management of broncho-pleural and alveolo-pleural fistulae.

Pneumothorax from bronchopleural or alveolo-pleural fistulae can be complicated by prolonged air leak (AL). This can occur in a variety of clinical settings. Examples include structural lung disease, such as bronchiectasis, and cavitary lung disorders. Prolonged AL is associated with prolonged hospital stay, atelectasis, pneumonia, and thromboembolic disease. Endobronchial valves (EBVs) have been recently introduced to manage such situations. The global experience in this novel therapeutic modality is still evolving. We report our preliminary experience with managing persistent AL treated successfully with EBVs and review the current literature on this subject. Our experience shows that EBVs are an effective tool for the management of prolonged AL from persistent bronchopleural or alveolo-pleural fistulae. It is a minimally invasive procedure recommended as an option, particularly in patients not fit for surgical repair.

A multicenter pilot study of a bronchial valve for the treatment of severe emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. OBJECTIVE: To study the safety and effectiveness of the IBV(R) Valve for the treatment of severe emphysema. METHODS: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. RESULTS: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (-8.2 +/- 16.2, mean +/- SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean -294 +/- 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV(1), exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. CONCLUSION: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.

Vaso-active therapy can improve 6-min walk distance in patients with pulmonary hypertension and fibrotic interstitial lung disease.

BACKGROUND: Dyspnea and functional limitation in interstitial lung diseases (ILD) are not always adequately explained by the degree of compromise in pulmonary function alone. Pulmonary hypertension (PH) is felt to be a major contributor to morbidity and mortality in these patients. It is not clear whether treatment with newer vaso-active agents benefits patients with PH in the setting of moderate or severe ILD. METHODS: Medical records of patients followed at our institution between July 2001 and June 2005 were reviewed to identify patients with moderate or severe fibrotic ILD and PH. Data regarding demographics, hemodynamics, and clinical characteristics at baseline and during follow-up were collected. RESULTS: We identified 19 patients who met our inclusion criteria and in whom vaso-active therapy [epoprostenol (N=10), bosentan (N=9)] was initiated. Most patients [(15/19(79%)] showed an initial positive response to therapy and improved their 6-min walk distance (6MWD) by >50m (responders) and 12/15 (80%) improved by at least 1 WHO functional class. At 1-year follow-up, 7 of 15 (47%) 'responders' had deteriorated significantly. None of the patients died during 1 year of follow-up. CONCLUSIONS: Epoprostenol and bosentan produced short-term functional benefit in our patients with PH and moderate or severe restrictive ILD. The generalizability of these results awaits the results of larger, prospective, randomized trials in such patients.

Hepatopulmonary syndrome following portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) and hepatopulmonary syndrome (HPS) are distinct clinical entities that may accompany liver disease. While PPHTN and HPS have been infrequently described as occurring in the same patient, to the present authors' knowledge, the order of occurrence has always been the initial onset of HPS, with pulmonary hypertension developing either concurrently or subsequently. In some instances, liver transplantation has been undertaken for HPS, followed by resolution of the HPS and subsequent development of pulmonary hypertension. The current case study presents a patient with hepatitis C-related cirrhosis in whom PPTHN developed initially, followed 2 yrs later by the development of the HPS. The current authors speculate that progressive imbalance in favour of endogenous vasodilators over vasoconstrictive factors led to normalisation of the pulmonary artery pressures.

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung.

Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM). The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung. The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity. In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.

Mycobacterium kansasii endobronchial ulcer in a nonimmunocompromised patient.

In this report we describe the case of an immunocompetent patient found to have an endobronchial, ulcerated lesion due to Mycobacterium kansasii. Predisposing factors could have been severe endobronchial stenosis of the main stem bronchi and distortion of the carina, due to healed endobronchial tuberculosis. Diagnosis was set through fiberoptic bronchoscopy and the patient responded well to treatment. Endobronchial non tuberculous mycobacterial infection should be considered in both HIV seropositive and seronegative patients, especially in endemic areas and in the proper clinical setting. Prompt recognition is important for the effective control and prevention of an unfavorable outcome in an otherwise easily treatable disease.

High-dose therapy and autologous stem cell transplant does not result in long-term disease-free survival in patients with recurrent chemotherapy-sensitive ALK-negative anaplastic large-cell lymphoma.

Primary systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) has a poor prognosis. This study sought to determine if high-dose therapy and ASCT results in long-term disease-free survival (DFS) in patients with recurrent, chemotherapy-sensitive ALK-negative ALCL. All patients with non-Hodgkin's lymphoma (NHL) who underwent ASCT at Wake Forest University and Upstate Medical University from 1 January 1990 to 12 December 2002 were reviewed to determine if they had T-, B- or null-cell NHL that was CD30+/CD15-/ALK negative. In all, 16 patients were thus identified as having ALK-negative ALCL. All 16 patients underwent ASCT at the time of first relapse and form the basis of this report. Median age of the 16 patients was 51 years. There were 11 males and five females. International prognostic index scores in 12 patients at the time of relapse were: low 3, LI 6 and HI 3. Of 15 patients, 13 relapsed after ASCT; one patient was lost to follow-up. Median progression-free survival for the 15 patients was 12 weeks (3-212+ weeks). Of 15 patients, 10 have died; nine of recurrent disease. Median overall survival for the 15 evaluable patients was 72 weeks. In our experience, high-dose therapy and ASCT does not produce long-term DFS in patients with recurrent chemotherapy-sensitive ALK-negative ALCL.

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.

Adult airway foreign body removal. What's new?

Signs and symptoms of adult FB aspiration are most often nonspecific. Misdiagnosis and delay in diagnosis frequently occur. Radiographic evaluation is helpful, but flexible bronchoscopy is the gold standard in the identification and localization of an airway foreign body. With increasing experience and development of better accessories, removal using a flexible bronchoscope under local anesthesia can be performed safely and successfully. Review of large series of FB removal indicates a success rate of 86% in more than 400 procedures with flexible bronchoscopy.

Training bronchoscopists for the new era.

Gustav Killian introduced bronchoscopy a little more than a century ago. At that time, the only way others could learn to perform bronchoscopy was by one-on-one tutoring, using a rigid bronchoscope with no side portals and no imaging devices such as a television camera and monitor. One-on-one teaching remains an integral part of learning how to perform bronchoscopy well, but many new technologies have emerged that make it far less labor intensive to train bronchoscopists. This article focuses on the training of bronchoscopists for the new era.

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients.

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.

Hypogammaglobulinemia in lung transplant recipients.

BACKGROUND: Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. METHODS: All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1-4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. RESULTS: Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl ("lowest IgG group") and 22 (33%) had IgG levels between 400 and 600 mg/dl ("moderately low IgG group"). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl ("normal IgG group"). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P=0.0006), bacteremias (P=0.02), total bacterial infections (P=0.002), tissue-invasive cytomegalovirus (P=0.01), invasive aspergillosis (P=0.001), total fungal infections (P=0.001), and total infections (P=0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P=0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P<0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. CONCLUSIONS: Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection.

Increased atherosclerosis in myeloperoxidase-deficient mice.

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its reaction products are present in human atherosclerotic plaque, and it has been proposed that MPO oxidatively modifies targets in the artery wall. We have now generated MPO-deficient mice, and show here that neutrophils from homozygous mutants lack peroxidase and chlorination activity in vitro and fail to generate chlorotyrosine or to kill Candida albicans in vivo. To examine the potential role of MPO in atherosclerosis, we subjected LDL receptor-deficient mice to lethal irradiation, repopulated their marrow with MPO-deficient or wild-type cells, and provided them a high-fat, high-cholesterol diet for 14 weeks. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls. Similar results were obtained in a genetic cross with LDL receptor-deficient mice. In contrast to advanced human atherosclerotic lesions, the chlorotyrosine content of aortic lesions from wild-type as well as MPO-deficient mice was essentially undetectable. These data suggest an unexpected, protective role for MPO-generated reactive intermediates in murine atherosclerosis. They also identify an important distinction between murine and human atherosclerosis with regard to the potential involvement of MPO in protein oxidation.

Therapeutic flexible bronchoscopy.

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.

Transbronchial needle aspiration of central and peripheral nodules.

Wang and Terry first described the technique of sampling of mediastinal lymph nodes using a flexible bronchoscope (FB) in 1983. Since then, the scope of transbronchial needle aspiration (TBNA) has increased enormously, and its value for diagnosis of central and peripheral lung lesions, even in the absence of endobronchial disease, is now recognized. Improvements in the diagnostic yield of TBNA aspirates, and increasing knowledge of predictors of a positive aspirate, has reduced the need for mediastinoscopy, and occasionally thoracotomy, with benefits in terms of reduced healthcare costs and improved patient welfare. Despite the fact that TBNA is a minimally invasive procedure, also for the staging of lung cancer, it unfortunately remains underutilized. This review aims to give the reader an overview of the indications, outcome data, technical considerations, and advantages of routinely performing TBNA. The technical suggestions to improve the yield from TBNA will hopefully provide greater understanding of this modality and help the pulmonologist to incorporate it in daily practice with more confidence.

The humoral immune response to influenza vaccination in lung transplant patients.

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients. Antibody levels to the three viral antigens included in the 1999-2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed. The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.

Progressive portopulmonary hypertension after liver transplantation treated with epoprostenol.

Portopulmonary hypertension (PPHTN) is an uncommon complication of advanced liver disease. Epoprostenol has been effective in the treatment of PPHTN and has been used as a bridge to orthotopic liver transplantation (OLT). The role of OLT in the reversal of PPHTN is unclear. We report a case of severe PPHTN (mean pulmonary artery pressure of 45 mm Hg) that progressed after OLT. Acute dosing with epoprostenol improved the pulmonary vascular resistance by 55% and the cardiac index by 134%. Hemodynamic and symptomatic improvements were maintained after 18 months of long-term treatment with epoprostenol. This is the first reported case of a successful favorable outcome after treatment for progressive PPHTN after OLT. Our case report complements previous reports by highlighting the potential effective use of epoprostenol as a definitive treatment for PPHTN.

The heat is on: impact of endobronchial electrosurgery on the need for Nd-YAG laser photoresection.

STUDY OBJECTIVES: Advances in bronchoscopic electrosurgery have allowed its application in the outpatient setting in patients who otherwise would have required Nd-YAG laser photoresection (LPR) in the operating room. We intended to evaluate the impact of endobronchial electrosurgery (EBES) on the need for Nd-YAG LPR on patients with symptomatic airway lesions. DESIGN: Prospective observational case series. PARTICIPANTS: One hundred eighteen evaluations for LPR were performed. Forty-seven evaluations (40%) were considered to be amendable to EBES and were treated during the initial bronchoscopy. The remaining patients underwent LPR. SETTING: Outpatient bronchoscopy suite at the Cleveland Clinic Foundation, Cleveland, OH. RESULTS: Of the 47 procedures, 42 (89%) were successful in alleviating the obstruction, thus eliminating the need for LPR. No major complications were encountered. CONCLUSION: EBES can be performed safely in the outpatient setting and is an effective procedure in treating select endobronchial lesions. EBES eliminated the need for LPR in 36% of such procedures with a potential for significant time and cost savings.