Paulo Francisco Guerreiro Cardoso

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.

Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation

BackgroundAirway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612).Methods/DesignThe multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1≤50% of predicted or FEV1 < 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit.DiscussionIf through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit.Trial RegistrationClinicalTrials.gov: NCT00391612

Lobectomia por carcinoma brônquico: análise das co-morbidades e seu impacto na morbimortalidade pós-operatória

OBJECTIVE: To analyze the impact that comorbidities have on the postoperative outcomes in patients submitted to lobectomy for the treatment of bronchial carcinoma. METHODS: A retrospective study of 493 patients submitted to lobectomy for the treatment of bronchial carcinoma was conducted, and 305 of those patients met the criteria for inclusion in the final study sample. The surgical technique used was similar in all cases. The Torrington-Henderson scale and the Charlson scale were used to analyze comorbidities and to categorize patients into groups based on degree of risk for postoperative complications or death. RESULTS: The postoperative (30-day) mortality rate was 2.9%, and the postoperative complications index was 44%. Prolonged air leakage was the most common complication (in 20.6%). The univariate analysis revealed that gender, age, smoking, neoadjuvant therapy and diabetes all had a significant impact on the incidence of complications. The factors found to be predictive of complications were body mass index (23.8 ± 4.4), forced expiratory volume in one second (74.1 ± 24%) and the ratio between forced expiratory volume in one second and forced vital capacity (0.65 ± 0.1). The scales employed proved efficacious in the identification of the risk groups, as well as in drawing correlations with morbidity and mortality (p = 0.001 and p < 0.001). In the multivariate analysis, body mass index and the Charlson index were found to be the principal determinants of complications. In addition, prolonged air leakage was found to be the principal factor involved in mortality (p = 0.01). CONCLUSION: Reductions in forced expiratory volume in one second, in the ratio between forced expiratory volume in one second and forced vital capacity, and in body mass index, as well as a Charlson score of 3 or 4 and a Torrington-Henderson score of 3, were associated with a greater number of postoperative complications in patients submitted to lobectomy for the treatment of bronchial carcinoma. Air leakage was found to be strongly associated with mortality.

Surgical treatment of bronchial carcinoid tumors: a single-center experience.

BACKGROUND Bronchial carcinoid is an infrequent neoplasm with a neuroendocrine differentiation. Surgical treatment is the gold standard therapy, with procedures varying from sublobar resections to complex lung sparing broncoplastic procedures. This study evaluates the results of surgical treatment of bronchial carcinoids and its prognostic factors. PATIENTS AND METHODS Retrospective review of 126 consecutive patients who underwent surgical treatment for bronchial carcinoid tumors between December 1974 and July 2007. RESULTS There were 70 females (55%) and the mean age was 46 years, ranging from 17 to 81 years. Upon clinical presentation, 38 patients (30%) have had recurrent respiratory tract infection, 31 (24%) cough, 16 (12%) chest pain and 25 (20%) were asymptomatic. Preoperative bronchoscopic diagnosis was obtained in 74 cases (58.7%). The procedures performed were: 19 sublobar resections (14,9%), 58 lobectomies (46%), 8 bilobectomies (6.3%), 6 pneumonectomies (4.7%), 2 sleeve segmentectomies (1.5%), 26 sleeve lobectomies (20.6%) and 9 bronchoplastic procedures without lung resection (7.1%). Operative mortality was 1.5% (n = 2) and morbidity was 25.8% (n=32), including 12 respiratory tract infections and 4 reinterventions due to bleeding (3) and pleural empyema (1). Among the 112 patients available for follow-up, the overall survival at 3, 5 and 10 years was 89.2%, 85.5% and 79.8%, respectively. Five and 10-year survival for typical and atypical carcinoids were 91, 89% and 56, 47%, respectively. Overall disease-free survival at 5 years was 91.9% Statistical analysis showed that overall disease-free survival correlated with histology--typical vs. atypical--(p = 0.04) and stage (p = 0.02). CONCLUSION Surgery provides safe and adequate treatment to bronchial carcinoid tumors. Histology and stage were the main prognostic factors.

Prevalência da doença do refluxo gastroesofágico em pacientes com fibrose pulmonar idiopática

OBJECTIVE To determine the prevalence of gastroesophageal reflux disease (GERD) and to evaluate its clinical presentation, as well as the esophageal function profile in patients with idiopathic pulmonary fibrosis (IPF). METHODS In this prospective study, 28 consecutive patients with IPF underwent stationary esophageal manometry, 24-h esophageal pH-metry and pulmonary function tests. All patients also completed a symptom and quality of life in GERD questionnaire. RESULTS In the study sample, the prevalence of GERD was 35.7%. The patients were then divided into two groups: GERD+ (abnormal pH-metry; n = 10) and GERD- (normal pH-metry; n = 18). In the GERD+ group, 77.7% of the patients presented at least one typical GERD symptom. The pH-metry results showed that 8 (80%) of the GERD+ group patients had abnormal supine reflux, and that the reflux was exclusively in the supine position in 5 (50%). In the GERD+ and GERD- groups, respectively, 5 (50.0%) and 7 (38.8%) of the patients presented a hypotensive lower esophageal sphincter, 7 (70.0%) and 10 (55.5%), respectively, presenting lower esophageal dysmotility. There were no significant differences between the groups regarding demographic characteristics, pulmonary function, clinical presentation or manometric findings. CONCLUSIONS The prevalence of GERD in the patients with IPF was high. However, the clinical and functional characteristics did not differ between the patients with GERD and those without.

Avaliação da resposta de pacientes asmáticos com refluxo gastroesofágico após terapia com pantoprazol: estudo prospectivo, randomizado, duplo cego e placebo-controlado

OBJECTIVES: To determine the effect that the treatment of GERD has on the clinical management, as well as the respiratory function, of patients with asthma and to evaluate the clinical characteristics of this group of patients. METHODS: Patients with asthma and concomitant GERD, documented using 24 h pH-metry, were evaluated by means of quality of life questionnaires, as well as questionnaires related to respiratory and digestive symptoms. In addition, esophageal manometry, spirometry and the determination of peak expiratory flow were also performed prior to and after the study. Forty-nine individuals who were diagnosed with GERD by means of 24 h esophageal pH-metry were selected and participated in a clinical randomized double-blind placebo-controlled study, involving the administration of 40 mg/day of pantoprazol for 12 consecutive weeks. RESULTS: Forty-four individuals completed the study (n = 22 per group). There was significant improvement in the scores for respiratory symptoms and quality of life only in the group that received pantoprazol (p = 0.01 and p = 0.001, respectively). No respiratory function parameters changed in either group. CONCLUSIONS: In this study, the effective treatment of GERD improved patient quality of life, and the symptoms of asthma significantly decreased in the group that received the medication. There were no changes in pulmonary function parameters.

Partial liquid ventilation with perfluorodecalin following unilateral canine lung allotransplantation in non–heart-heating donors

Abstract Background The purpose of this study was to evaluate canine lungs obtained from non–heart-beating donors after unilateral lung transplantation subjected to partial liquid ventilation with perfluorodecalin. Methods Twelve donor dogs were killed and kept under mechanical ventilation for 3 hours. Heart–lung blocs were harvested after retrograde pulmonary hypothermic flush with Perfadex. Left lung grafts were randomly transplanted into 12 weight-matched recipient animals. Animals were divided into 2 groups: control (standard mechanical ventilation, n = 6) and PLV (partial liquid ventilation, n = 6). Forty-five minutes after transplantation, the animals in the PLV group received perfluorodecalin (15 ml/kg) via orotracheal tube. All animals received volume-controlled ventilation (Fio 2 1.0, PEEP 5 cm H 2 O) over 6 consecutive hours. Thereafter, blood-gas analysis, ventilatory mechanics and hemodynamics were registered at 30-minute intervals. After 6 hours of reperfusion the animals were killed and the transplanted lungs were extracted to obtain the wet/dry weight ratio. Results There were significant differences in pulmonary arterial pressure, which were higher in control group animals ( p 2 than those in the PLV group ( p 2 ( p p Conclusions PLV with perfluorodecalin yields functional results compatible with life in this model. Nonetheless, pulmonary gas exchange and mechanics were superior after reperfusion in animals given conventional mechanical ventilation up to 6 hours after left lung allotransplantation.

Airway bypass treatment of severe homogeneous emphysema: taking advantage of collateral ventilation.

Airway bypass is being investigated as a new form of minimally invasive therapy for the treatment of homogeneous emphysema. It is a bronchoscopic catheter-based procedure that creates transbronchial extra-anatomic passages at the bronchial segmental level. The passages are expanded, supported with the expectation that the patency is maintained by paclitaxel drug-eluting airway bypass stents. The concept of airway bypass has been demonstrated in two separate experimental studies. These studies have shown that airway bypass takes advantage of collateral ventilation present in homogeneous emphysema to allow trapped gas to escape and reduce hyperinflation. It improves lung mechanics, expiratory flow, and volume. Airway bypass stent placements have been shown to be feasible and safe in both animal and human studies. Paclitaxel-eluting airway bypass stents were found to prolong stent patency and were adopted for clinical studies. A study evaluating the early results of the clinical application of airway bypass with paclitaxel-eluting stents found that airway bypass procedures reduced hyperinflation and improved pulmonary function and dyspnea in selected subjects who have severe emphysema. The duration of benefit appeared to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results supported further evaluation of the procedure and led to the EASE Trial. The EASE Trial is a prospective, multicenter, randomized, double-blind, sham-controlled study. The trial aims to evaluate the safety and effectiveness of the airway bypass to improve pulmonary function and reduce dyspnea in homogeneous emphysema subjects who have severe hyperinflation. The trial is presently ongoing worldwide, though enrollment was completed.

Estado atual e aplicabilidade clínica da punção aspirativa por agulha guiada por ultrassom endobrônquico

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has played a key role in the diagnosis of mediastinal, paratracheal, and peribronchial lesions, as well as in lymph node staging for lung cancer. Despite its minimally invasive character, EBUS-TBNA has demonstrated a diagnostic yield comparable with that of established surgical methods. It has therefore gained credibility and has become a routine procedure at various referral centers. A successful EBUS-TBNA procedure requires careful planning, which includes a thorough review of the radiological imaging and special care during specimen collection and preparation, as well as technical expertise, experience with the procedure itself, and knowledge of the potential complications inherent to the procedure. The most common indications for EBUS-TBNA include lymph node staging for lung cancer and the diagnostic investigation of mediastinal/hilar masses and lymph node enlargement. Recently, tumor biomarkers in malignant samples collected during the EBUS-TBNA procedure have begun to be identified, and this molecular analysis has proven to be absolutely feasible. The EBUS-TBNA procedure has yet to be included on the Brazilian Medical Association list of medical procedures approved for reimbursement. The EBUS-TBNA procedure has shown to be a safe and accurate tool for lung cancer staging/restaging, as well as for the diagnosis of mediastinal, paratracheal, and peribronchial lesions/lymph node enlargement

Predictors for Postoperative Complications After Tracheal Resection

BACKGROUND Tracheal resection and anastomosis is the gold standard for the treatment of tracheal stenosis. The objective of this study is to evaluate the complications after tracheal resection for benign stenosis and the predicting factors for such complications. METHODS A retrospective study was made involving patients with benign tracheal or laryngotracheal stenosis who underwent surgical resection and reconstruction between February 2002 and January 2009. Complications related and unrelated to the anastomosis were studied. Categorical variables were presented as percentage and continuous variables as mean and standard deviation. Predicting factors were determined by univariate analysis. Factors with p less than 0.05 were used for multivariate regression. Logistic regression models were also employed for dependent variables. Statistical significance was set for p less than 0.05. RESULTS Ninety-four patients (18 female, 76 male) were included. Complications occurred in 42 (44.6%). Twenty-one percent had anastomotic complications. The most common complication was restenosis (16%). Nonanastomotic complications occurred in 23.2%. Wound infection occurred in 10.6%. Clinical comorbidities, previous tracheal resection, and the length of tracheal resection were statistically significant factors for complications. Previous tracheal resection was the most significant factor and was highly associated with anastomotic complications (odds ratio 49.965, p=0.012). The greatest number of complications was found in the laryngotracheal reconstruction group, and in resections more than 4 cm. Mean follow-up was 19±14 months. At the end of the study, 86 patients (91.4%) were breathing normally. There was no mortality in this series. CONCLUSIONS Comorbidities, previous tracheal resection, and the length of tracheal resection more than 4 cm were statistically significant factors for the onset of complications.