Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

BACKGROUND: Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. METHODS: We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. FINDINGS: All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). INTERPRETATION: Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. FUNDING: Broncus Technologies.

Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

BACKGROUND: Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). METHODS: In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. RESULTS: Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. CONCLUSIONS: There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

Impaired detection of Mycobacterium tuberculosis immunity in patients using high levels of immunosuppressive drugs.

We have previously shown, in renal transplant recipients on maintenance immunosuppression, that a whole-blood assay was superior in detecting immunity towards purified protein derivative (PPD) compared with skin testing. As blood tests may have limitations during high-dose immunosuppression therapy, the present study was aimed at characterising the effect of high immunosuppressive drug levels on PPD-specific T-cell immunity. PPD-reactive CD4 T-cells from 13 renal transplant recipients were longitudinally quantified by the induction of cytokines using flow cytometry. To further address the effect of high and low maintenance immunosuppression, drug effects were studied in vitro and in 49 age-matched lung transplant recipients and 49 renal transplant recipients. Maintenance immunosuppression after renal transplantation did not affect PPD-specific T-cell detection (median T-cell frequencies 0.55% before and 0.46% >12 months after transplantation), whereas specific T-cell frequencies were significantly lower 3 months after transplantation (0.15%; p = 0.0002). Likewise, high-level maintenance immunosuppression after lung transplantation was associated with a significantly lower prevalence in PPD-specific T-cell reactivity compared with renal transplant recipients (16.7% versus 52.1%; p = 0.0005). In line with the observations made in vivo, calcineurin inhibitors analysed in vitro led to a dose-dependent decrease in antigen-specific T-cell reactivity. The flow cytometric assay is not adversely affected by low drug doses. In contrast, decreased levels of PPD-specific T-cells early after transplantation and low prevalence of PPD-reactivity in lung transplant recipients suggest a reduced sensitivity of in vitro testing during high-level immunosuppression.

[Massive pleural effusion complicating chronic pancreatitis. Treatment by endoscopic closure of a pancreatic-mediastinal fistula]. / Ausgedehnter Pleuraerguss bei chronischer Pankreatitis. Behandlung durch endoskopischen Verschluss einer pankreatikomediastinalen Fistel.

HISTORY AND CLINICAL FINDINGS: A 53-year-old man was admitted because of anuria, dyspnea and a septic temperature. The patients' history included chronic alcoholism, chronic pancreatitis, COPD and a right nephrectomy because of nephrolithiasis. Urosepsis was initially suspected. INVESTIGATIONS: The patients' clinical condition and nutritional state were severely reduced. Laboratory findings revealed severe systemic inflammation (leucocyte count: 22.4/nl, CRP: 324 mg/l). Computed tomography showed a large left-sided pleural effusion, encapsulated abdominal fluid below the diaphragm and alongside the pancreatic tail. After aspiration of the pleural effusion the diagnosis of an exsudate with elevated concentration of lipase (56,000 U/l) was confirmed. Endoscopic ultrasound showed a 3-4 cm pseudocystic mass originating in the region of the pancreatic tail. The ERP depicted chronic pancreatitis with strictures and destruction of the pancreatic duct. Two fistulae were identified, one proximal to a ductal stricture in the pancreatic head and a second one in the pancreatic tail which corresponded to the reported pseudocyst. TREATMENT AND CLINICAL COURSE: The patient was admitted to the ICU with symptoms of impending sepsis. The pleural effusion was treated with CT-guided chest drainage. The initial endoscopic attempt at stent closure of the fistula failed because it was possible to pass through the ductal stricture only with a thin hydrophilic wire and small-lumen catheter. However, injection of fibrin glue into the proximal pancreatic duct over a length of 2 cm obliterated the fistula and the pleural effusion was resolved. CONCLUSION: Pancreatic-pleural or pancreatic-mediastinal fistula is a rare complication of pancreatitis associated with unilateral pleural effusion. Combined internal endoscopic drainage and external chest drainage is the treatment of choice. After failure of routine endoscopic therapy, endoscopic closure of fistulas using fibrin glue might offer an alternative treatment strategy.

[Coincident manifestation of mesotheliomas of the tunica vaginalis and pleura. Case report and literature overview]. / Gleichzeitige Manifestation von Mesotheliomen der Tunica vaginalis und der Pleura. Kasuistik und Literaturübersicht.

Malignant mesotheliomas are rare entities (0.1-0.2% of all malignant tumors) possibly localized at the pleura, peritoneum, pericardium, and tunica vaginalis. Most malignant mesotheliomas are caused by asbestos inhalation. We report on a man who suffered from malignant mesotheliomas of the tunica vaginalis and of the pleura simultaneously. The development of these tumors was probably multicentric; the patient had been exposed to asbestos over a period of 22 years. We discuss the individual findings and the current literature.

[Ineffective anticoagulation prior to elective electric cardioversion for atrial fibrillation. Results of transesophageal echocardiography]. / Ineffektive Antikoagulation vor elektiver elektrischer Kardioversion von Vorhofflimmern. Befunde der transösophagealen Echokardiographie.

BACKGROUND AND OBJECTIVE: Anticoagulation (AC) should be given for 3 to 4 weeks before elective electrical cardioversion to reduce thromboembolic events. During this period ineffective AC is a common problem. The aim of our study was to investigate the influence of the duration of ineffective AC on the incidence of left atrial thrombi (LAT) or spontaneous echocontrast (SEC) induced by hemostasis detected by transesophageal echocardiography (TEE). PATIENTS AND METHODS: 56 consecutive patients (39 men) at the age of 64 +/- 9 years with non-rheumatic atrial fibrillation who were scheduled for electrical cardioversion after 3 to 4 weeks of AC and a documented ineffective AC underwent TEE. Cardioversion was performed after exclusion of a LAT by TEE or in patients with LAT after 4 more weeks of AC and repeated TEE. All patients received AC and were observed for at least 4 weeks after cardioversion. Echocardiographic, demographic and clinical parameters and available values of AC were recorded. RESULTS: In 5/56 (9 %) patients a LAT, in 10 (18 %) patients SEC was detected. No patient had both. In patients with LAT the duration of ineffective AC was 15 +/- 10 days (range 5 - 28) and did not differ significantly from patients without LAT (17 +/- 8 days; range 0 - 28) or to the group with SEC (23 +/- 6 days; range 12 - 28). There was no significant difference of demographic, echocardiographic and clinical parameters between these groups. There was no embolic event during follow-up. CONCLUSIONS: Neither the duration of ineffective AC nor clinical, epidemiologic or echocardiographic parameters could differentiate patients with or without LAT in our observed groups with small numbers of patients. In case of an ineffective AC patients who are to undergo electrical cardioversion should have TEE. In our study patients with SEC were not at a higher thromboembolic risk.

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.

BACKGROUND: The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown. METHODS AND RESULTS: In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment. CONCLUSION: An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial.

The aim of this study was to investigate formoterol, an inhaled long-acting beta2-agonist, in patients with chronic obstructive pulmonary disease (COPD). Six-hundred and ninety-two COPD patients, mean baseline forced expiratory volume in one second (FEV1) 54%, FEV1/forced vital capacity 75% of predicted, reversibility 6.4% pred, were treated with formoterol (4.5, 9 or 18 microg b.i.d.) or placebo via Turbuhaler for 12 weeks. Symptoms were recorded daily. Spirometry and the incremental shuttle walking test (SWT) were performed at clinic visits. Compared with placebo, 18 microg b.i.d. formoterol reduced the mean total symptom score by 13% and increased the percentage of nights without awakenings by 15%. Formoterol (9 and 18 microg b.i.d.) significantly reduced symptom scores for breathlessness (-7% and -9%, respectively) and chest tightness (-11% and -8%, respectively), reduced the need for rescue medication (-25% and -18%, respectively), and increased symptom-free days (71% and 86%, respectively). FEV1 improved significantly after all three doses of formoterol (versus placebo). No differences were found between groups in SWT walking distance. No unexpected adverse events were seen. In conclusion, 9 and 18 microg b.i.d. formoterol reduced symptoms and increased the number of symptom-free days in a dose-dependent manner in chronic obstructive pulmonary disease patients. Formoterol improved lung function at a dose of 4.5 microg b.i.d. and higher.

Use of HL7 to integrate a HIS-subsystem: limits and possibilities.

Modern computer-based hospital information systems are mostly distributed with several heterogeneous subsystems connected together by specialized communication services. The common standard to integrate subsystems is HL7. By the example of subsystem integration for a pulmonary function test lab, we discuss the possibilities of HL7, the limits we encountered and how we overcame these.

Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension.

BACKGROUND: The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors. METHODS AND RESULTS: The short-term effects of 8.4 to 10.5 microgram of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4+/-1.3 versus 6.4+/-1.1 mm Hg; P<0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8+/-1.4 versus 9.4+/-1.3 mm Hg; P<0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects. CONCLUSIONS: Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.

[Accuracy of positron emission tomography with fluorine-18-fluoro-deoxyglucose]. / Aussagekraft der Positronen-Emissions-Tomographie mit F-18-Fluordesoxyglukose (FDG-PET) beim Bronchioloalveolarzellkarzinom (BAC).

BACKGROUND: : FDG-PET is a powerful tool for the diagnostic workup of patients with lung cancer. A reduced sensitivity of FDG-PET for the evaluation of lung lesions was reported for bronchioloalveolar carcinoma (BAC). No literature exists about the diagnostic efficacy of FDG-PET in the staging of BAC. METHODS: : Out of a series of subsequent 630 untreated patients with the final diagnosis of lung cancer, who underwent FDG-PET, all patients with BAC were evaluated with respect to tumour detection, N-staging, and M-staging. RESULTS: : 35 patients (5.6 %) had BAC, 22 in a localized form (8 x pT1, 14 x pT2), 13 in a disseminated stage. FDG-PET correctly identified 19/22 cases with localized forms. Two of the missed one were classified as pT1. All disseminated forms of BAC were detected. Standardized uptake values (SUV) ranged from 0.9 to 23.3 (mean +/- SD: 11.6 +/- 5.1). Accuracy of N-staging was comparable to known results in lung cancer (FDG-PET 80 %, CT 64 %). With respect to M-staging, sensitivity of FDG-PET was as follows: M1(HEP): 2/3 (67 %), M1(PUL): 7/8 (88 %), M1(OSS): 1/1 (100 %). CONCLUSIONS: : With some limitations in small localized tumours FDG-PET can detect and stage BAC with an accuracy which is identical to that for other histological types of non-small cell lung cancer.

[Efficacy of demand oxygen delivery systems in patients with chronic obstructive lung disease]. / Effektivität von Sauerstoff-Demand-Systemen bei Patienten mit chronisch obstruktiver Atemwegserkrankung.

To maintain mobility in patients with chronic hypoxemia who are under long-term oxygen therapy, portable oxygen systems are available. They have the disadvantage of a short range. To prolong the range and to reduce the cost of oxygen treatment, demand oxygen delivery systems (DODS) are used. Aim of the study was to compare three DODS (DOC-2000 [D], TransTracheal Inc.; Oxytron [O], Weinmann; Pulsair [P], DeVilbiss, Sunrise Medical) with continuous oxygen delivery. 17 patients (age 67.82 +/- 9.46 years; FEV1 1.23 +/- 0.69 l; PaO2 48.8 +/- 6.7 mm Hg) were studied. The continuous flow oxygen (CONT) and the DODS were applied to the patients for 30 minutes each in random sequence with an airflow of 2 l/min. After 15 and 30 minutes arterial blood gas analysis was done. Oxygen saturation was recorded continuously by pulseoximetry. After 15 minutes no significant differences in PaO2 were found between CONT and DODS. After 30 minutes no significant difference in PaO2 was found in CONT as compared to P. Significant lower PaO2 values were found for O and D as compared to CONT (p < 0.01). With P the range of a portable oxygen source was increased by 161.5 percent, with O by 172 percent, with D the range was increased by only 17.2 percent. Prolongation of range of a portable oxygen source can be achieved by means of DODS without a decrease of PaO2 and thus without loss of quality of the oxygen treatment. However, there are differences in efficacy between the DODS.

[Interferon alpha-2a in the treatment of diffuse thoracic angiomatosis in adulthood--a ase report]. / Interferon alpha-2a zur Therapie einer diffusen thorakalen Angiomatose im Erwachsenenalter--Ein Fallbericht.

A diffuse angiomatosis affecting thoracal organs is a rare, frequently fatal disorder occurring mainly in childhood. The definite diagnosis is usually made by autopsy. A specific treatment does not exist. In the case report presented here we describe the course of an 37-year old patient presenting initially with dyspnea and hemoptysis. Radiological investigations showed a mass lesion in the anterior superior mediastinum, bihilar masses and a periesophageal mass with soft tissue density and a pericardial effusion. Bilateral interstitial infiltrations were also present. CT-guided mediastinal biopsies and bronchial mucosal biopsies were nonspecific. Open-lung biopsy revealed the diagnosis of an extensive diffuse angiomatosis affecting mediastinum, pericardium and pleura. During the 18-month monotherapy with interferon-alpha 2a the patient showed significant improvements of clinical as well as laboratory and radiological parameters. The presented case confirms the experience of several authors, that the diagnosis of a diffuse thoracal authors can only be made by open lung biopsy or autopsy. The presented case also underlines the possibility of a palliative therapy of aggressive angiomatous diseases with interferon-alpha 2a.