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.

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.

Gorham's syndrome: a case report and review of the literature.

Gorham's syndrome is a rare disorder involving a proliferation of vascular channels associated with extensive loss of bony matrix. A case report is presented with a review of the 97 previously reported cases. The age of patients at presentation has ranged from less than one to 75 years (mean: 27 years). Sixty-four percent have been men. Fifty-seven percent have had a history of prior trauma. Laboratory values for systemic measures have usually been normal. The disease usually arrests spontaneously, but this is unpredictable. Sixteen patients (16 percent) have died of the disorder, with 10 deaths due to chest wall involvement, three to spinal cord transection, two to sepsis, and one to asphyxia and aspiration. Although the mechanism of bone loss is unknown, osteoclasts were focally increased in the case described herein. Further information and investigation are needed to better understand this unusual disorder.

A new class of antimalarial drugs: derivatives of benzothiopyrans.

A series of substituted benzothiopyrans was synthesized and examined for antimalarial activity. Some were found to be active and curative at dose levels of 160--360 mg/kg against Plasmodium berghei in mice. Afew observations concerning structure-activity relationships were made. The benzothiopyrans were prepared by treatment of either the gem-dichloro- or the thionothioflavone intermediate with various primary amines. The thionothioflavone intermediates were made from thioflavones. Condensation of thiophenols with benzoyl acetates gave the thioflavones.

Increased alveolar macrophage nuclear factor-kappa B activation and macrophage inhibitory protein-1alpha levels in lung transplant patients.

BACKGROUND: Lung transplantation is increasingly used as the treatment for many end-stage pulmonary diseases. A major cause of morbidity and mortality in patients who undergo lung transplantation is rejection of the allograft. Proinflammatory macrophage-derived cytokines may sustain and/or enhance the immunological response to lung allograft antigens. Nuclear factor-kappa B (NF-kappaB) is a transcription factor that regulates the production of many of these cytokines and growth factors in alveolar macrophages (AMs). The aim of our study was to evaluate the activation of NF-kappaB in AMs and the levels of one of the proinflammatory cytokines whose production it controls, macrophage inhibitory protein-1alpha (MIP-1alpha), in AMs from transplanted lungs compared to those from healthy controls. METHODS: Twenty-eight (28) transplant recipients were included in the study. NFkappaB activation was evaluated by electrophoretic mobility shift assay of whole cell extracts and by immunohistochemical analysis on cytospin preparations. Concentrated bronchoalveolar lavage fluid was analyzed by enzyme-linked immunosorbent assay for MIP-1alpha levels. RESULTS: NF-kappaB was activated in alveolar macrophages from transplant patients as compared to healthy controls. MIP-1alpha levels in epithelial-lining fluid were elevated in transplant patients as compared to healthy controls. Increased MIP-1alpha levels correlated with viral infections in the transplant patients. Neither finding was found to correlate with acute rejection by transbronchial biopsy. CONCLUSIONS: These results demonstrate that NF-kappaB activation and MIP-1alpha levels are increased in transplanted lungs and may play a role in the inflammatory cytokine cascade that leads to the long-term tissue damage and allograft rejection in these patients.

A multivariate analysis of risk factors for pneumonia following cardiac transplantation.

Fifty cardiac transplant recipients were followed over a 34-month period for evidence of pneumonia that developed in twelve patients. Potential risk factors evaluated fell into three categories: demographic (age, sex, race, and underlying cardiac disease); pretransplant status (hospitalized, intubated, pulmonary infiltrate, requirement for antibiotics, or the need for a ventricular assist device); and posttransplant therapy (amount and type of blood products, prolonged endotracheal intubation or reintubation, use of ventricular assist devices, immunosuppressive protocols, lymphocyte subset ratios, and occurrence of rejection, leukopenia, or CMV infection). The Cox proportional hazards model identified posttransplant reintubation (P = 0.009) and the use of protocols employing larger steroid dosages (P = 0.02) as significant risk factors for pneumonia. In a separate analysis, the occurrence of pneumonia was shown to be a significant risk factor for mortality (P = 0.018).

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.

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.

Biopsy excision through a fiberoptic bronchoscope in the palliative management of airway obstruction.

Simple biopsy resection through the rigid bronchoscope has been described in the past. We successfully performed such resection through a flexible bronchoscope in six patients with symptomatic and relatively less vascular lesions without complications. In selected patients simple biopsy resection of endobronchial lesion can be safely performed through flexible bronchoscope.

Necrosis of the bronchus. Role of radiation.

The effects of radiation on the lung parenchyma and pleura are well described in the literature. Necrosis of the larynx is a known complication of radiation therapy. Necrosis of a part of the tracheobronchial tree following radiation therapy for bronchogenic carcinoma is likely to occur; however, there is little mention in the English-language literature about such an effect. This report describes four cases with total necrosis of a specific bronchus following radiation therapy for squamous cell carcinoma of the lung. All patients received 5,000 to 6,400 rad (50 to 64 Gy) of external-beam radiation. Two patients presented with massive hemoptysis and two with pneumonia. In all four cases, the patients were found to have, by bronchoscopy, necrosis of the bronchus with the involved lobe of the lung replaced by a large cavity lined by tumor tissue. Diagnosis was made 5 to 7 months after radiation therapy was completed. Three of the patients died of exsanguination within weeks following diagnosis of the complication. We suspect that such necrosis occurs as a consequence of radiation therapy in combination with infection in the set up of squamous cell carcinoma, and is a marker of poor prognosis.

Management of airway manifestations of relapsing polychondritis: case reports and review of literature.

STUDY OBJECTIVE: To report the first series of patients with severe airway manifestations of relapsing polychondritis (RP) that were managed successfully with self-expandable metallic stents, and to review the literature. DESIGN: Retrospective review of medical records, and current clinical follow-up. SETTING: Tertiary care referral hospital. PATIENTS: All patients with airway manifestations of RP that were managed with self-expandable metallic stents at our institution. RESULTS: All five patients (four women and one man; age, 40 to 69 years old) had severe airway manifestations, and three of them required mechanical ventilation. Spirometry with flow-volume curves showed severe combined obstructive and restrictive ventilatory defects. Bronchoscopy revealed dynamic collapse of the proximal airways. Diagnosis was made 8 months to 13 years after the first symptom of the disease. Pharmacotherapy included prednisone, methotrexate, cyclosporine, and dapsone. A total of 17 self-expandable metallic stents of varying sizes were placed using flexible bronchoscope from 4 to 19 years after the first symptom. The overall outcome was favorable in four patients. Three patients have survived without ventilatory support 16 to 18 months following the first stent placement, and the fourth patient survived for 20 months without ventilatory support before she died. The fifth patient, who was receiving mechanical ventilation, died in 1 week probably due to persistent dynamic collapse of the airways distal to the stents. CONCLUSION: Self-expandable metallic tracheobronchial stents should be considered in the management of airway manifestations of RP, especially in patients who require mechanical ventilation.

Captopril-induced cough.

Since the advent of angiotensin-converting enzyme inhibitors (captopril and enalapril), cough has been recognized sporadically as a side effect, but has received little attention in the pulmonary literature. To emphasize that angiotensin-converting enzyme (ACE) inhibitors should be considered among possible etiologies of cough, we report recent experience with two patients and review the available experience with ACE inhibitor-induced cough.

Air embolism in single-lung transplant patients after central venous catheter removal.

A 53-year-old woman had a serious air embolism from the central venous catheter tract after lung transplantation. Lung transplant patients appear to be at increased risk for this complication, and four other known cases are reported.

Is direct collection of pleural fluid into a heparinized syringe important for determination of pleural pH? A brief report.

INTRODUCTION: It has long been believed that pleural fluid must be directly aspirated into a heparinized syringe to obtain an accurate value. Many operators aspirate 30 to 60 mL of pleural fluid into a syringe without heparin, and then place 1 mL into a heparinized syringe from which the pH is determined. We postulated that this technique does not cause a clinically significant difference in pleural pH values. METHODS: Patients undergoing thoracentesis in the outpatient clinic, general ward, and medical ICU were eligible. After the initial entry of the needle into the pleural space, a heparinized syringe was used to obtain pleural fluid for pH determination. A 60-mL syringe was then used to aspirate additional pleural fluid for biochemical analysis and culture. At the end of the procedure, a second aliquot of pleural fluid was placed into a heparinized syringe for pH determination. A difference of 0.1 in pH was taken as clinically important. RESULTS: Twenty-one pleural fluid samples were obtained from 20 patients. Pleural fluid pH determinations were within 0.1 in all but one patient. The mean pH for the directly collected group was 7.39 (25%: 7.35; 75%: 7.45). The mean for the indirectly collected group was 7.41 (25%: 7.35; 75%: 7.45). The difference between the two means (0.02; 95% confidence interval, 0.0368 to 0.00131) was statistically significant but clinically unimportant (p=0.037). CONCLUSIONS: Pleural fluid can be collected in a large syringe and then placed into a heparinized syringe to assess pH. This is useful information because the use of just one syringe saves time and reduces the risk of iatrogenic complications.

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.

Right-to-left interatrial shunt causing platypnea after pneumonectomy. A recent experience and diagnostic value of dynamic magnetic resonance imaging.

Shortness of breath after pneumonectomy is a common finding that has multiple causes. We report the cases of two patients with shortness of breath on assuming an upright posture (platypnea) that followed pneumonectomy; these individuals developed right-to-left shunt across a patent foramen ovale (PFO) with normal right-sided intracardiac pressures. Both contrast echocardiography and magnetic resonance imaging (MRI), including a recently introduced dynamic ultrafast imaging technique, proved helpful in diagnosing this condition noninvasively.

Endobronchial and parenchymal juvenile laryngotracheobronchial papillomatosis. Effect of photodynamic therapy.

Juvenile laryngotracheobronchial papillomatosis (JLTBP) is a recurrent, prolonged disease usually confined to the upper airway. Rarely, tracheobronchial tree or lung parenchymal involvement occurs. The various therapeutic interventions are often unsuccessful once extralaryngeal involvement becomes apparent. Photodynamic therapy (PDT) has been successful in eradicating JLTBP in a few case reports. We present a case of extensive JLTBP with parenchymal involvement treated with multiple courses of PDT. We demonstrated temporary regression of endobronchial papillomas, but no change in parenchymal lesions. Recurrent endobronchial disease was most likely related to reinfection from parenchymal lesions inaccessible to PDT.

The safety of outpatient transbronchial biopsy.

Fiberoptic bronchoscopy (FOB) is an accepted outpatient procedure, but transbronchial biopsy (TBB) is generally reserved for hospitalized patients. Over a three-year period, we performed fluoroscopically guided TBB in 148 of 688 outpatients undergoing FOB. Following the procedure, fluoroscopy was used to screen for possible pneumothorax in those patients who had had TBB. All patients were observed for one hour and then discharged if stable. Three patients (2.02 percent) were admitted and observed for acute hemoptysis following TBB. Bleeding ceased spontaneously in each. The remaining 145 patients were discharged after one hour of observation. One patient (0.68 percent) required Heimlich tube treatment for a delayed pneumothorax. Our experience indicates a low incidence of delayed complications in patients who are asymptomatic for one hour following TBB. We conclude that patients do not require hospitalization solely for TBB.