David Stav

High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema

OBJECTIVE To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Effect of N-Acetylcysteine on Air Trapping in COPD: A Randomized Placebo-Controlled Study

BACKGROUND FEV(1) is used for the classification of disease severity and is a good predictor of COPD mortality. However, it is a poor predictor of clinical symptoms, exercise tolerance, and response to bronchodilators in COPD. Progressive reduction in inspiratory capacity (IC) during exercise reflects dynamic hyperinflation and is a good predictor of decreased exercise ability as well as increased exertional dyspnea. In animal models of COPD, N-acetylcysteine (NAC), an antioxidant/mucous modifier, has been shown to modify small airways, which mainly causes lung hyperinflation. OBJECTIVE Our goal was to examine the effect of 1,200 mg/d of NAC on lung hyperinflation at rest and after exercise in patients with moderate-to-severe COPD. METHODS This was a randomized, double-blind, cross-over study that included 24 eligible patients > 40 years of age with a diagnosis of COPD, a FEV(1) < 70% of predicted, FEV(1)/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to placebo treatment or NAC treatment twice daily for 6 weeks. This was followed by a 2-week washout period, and then patients were crossed over to alternate therapy for an additional 6 weeks. Evaluation was performed after each 6 weeks of each treatment. RESULTS IC and FVC were higher especially after exercise after NAC treatment compared with placebo treatment. In addition, the relationship of residual volume to total lung capacity was reduced in a similar pattern. Furthermore, endurance time was longer after NAC treatment compared with placebo treatment. CONCLUSIONS NAC treatment of patients with stable, moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00476736.

Three years of pulmonary rehabilitation: inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease.

BackgroundPulmonary rehabilitation is known to be a beneficial treatment for COPD patients. To date, however, there is no agreement for how long a rehabilitation program should be implemented. In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients. The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI).MethodsA matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months. Eighty patients with moderate to severe COPD (age 63 ± 7 years; FEV1 48% ± 14) were recruited. The control group received standard care only, while in addition, the case study group received PR for duration of three years. These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked.ResultsThe decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001). Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01). A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05).ConclusionThree years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients.

Thoracic Empyema in High-Risk Patients: Conservative Management or Surgery?

We retrospectively analyzed the data of 119 patients who were treated for empyema thoracis from 1999 to 2007. There were 87 men with a mean age of 63.9 years (range, 19–79 years) and 32 women with a mean age 55.2 years (range, 26–78 years). The empyema was right-sided in 73 patients and left-sided in 46. The etiology was parapneumonic in 43.7% of cases, postoperative in 42.0%, posttraumatic in 11.8%, and due to other causes in 2.5%. Eight (6.7%) patients underwent surgery on admission because of unstable clinical status; all 8 survived. Fibrinolysis was used in 111 (93.3%) patients; of these, 88 (73.9%) were successfully treated by intrapleural urokinase instillation, and 23 (19.4%) failed treatment and underwent surgery. All 88 patients who had successful fibrinolytic therapy survived, they accounted for 1.8% of the morbidity. In the 23 patients who underwent surgery after failed treatment, there were 3 deaths, accounting for 2.7% overall mortality and 6.3% morbidity. Treating thoracic empyema in patients with significant comorbidities is challenging. Intrapleural urokinase administration might be beneficial in high-risk patients, but in those without significant comorbidities, early surgery may be considered.

Gene expression subtraction of non-cancerous lung from smokers and non-smokers with adenocarcinoma, as a predictor for smokers developing lung cancer

BackgroundLung cancer is the commonest cause of cancer death in developed countries. Adenocarcinoma is becoming the most common form of lung cancer. Cigarette smoking is the main risk factor for lung cancer. Long-term cigarettes smoking may be characterized by genetic alteration and diffuse injury of the airways surface, named field cancerization, while cancer in non-smokers is usually clonally derived. Detecting specific genes expression changes in non-cancerous lung in smokers with adenocarcinoma may give us instrument for predicting smokers who are going to develop this malignancy.ObjectivesWe described the gene expression in non-cancerous lungs from 21 smoker patients with lung adenocarcinoma and compare it to gene expression in non-cancerous lung tissue from 10 non-smokers with primary lung adenocarcinoma.MethodsTotal RNA was isolated from peripheral non-cancerous lung tissue. The cDNA was hybridized to the U133A GeneChip array. Hierarchical clustering analysis on genes obtained from smokers and non-smokers, after subtracting were exported to the Ingenuity Pathway Analysis software for further analysis.ResultsThe genes subtraction resulted in disclosure of 36 genes with high score. They were subsequently mapped and sorted based on location, cellular components, and biochemical activity. The gene functional analysis disclosed 20 genes, which are involved in cancer process (P = 7.05E-5 to 2.92E-2).ConclusionDetected genes may serve as a predictor for smokers who may be at high risk of developing lung cancer. In addition, since these genes originating from non-cancerous lung, which is the major area of the lungs, a sample from an induced sputum may represent it.

Morbidity and Mortality after Major Pulmonary Resections in Patients with Locally Advanced Stage IIIA Non-small Cell Lung Carcinoma Who Underwent Induction Therapy

BACKGROUND The optimal treatment for patients with locally advanced stage IIIA non-small cell lung carcinoma (NSCLC) remains controversial, but induction therapy is increasingly used. The aim of this study was to evaluate mortality, morbidity, hospital stay and frequency of postoperative complications in stage IIIA NSCLC patients that underwent major pulmonary resections after neoadjuvant chemotherapy or chemoradiation. METHODS We conducted a retrospective analysis of all patients who underwent major pulmonary resections after induction therapy for locally advanced NSCLC from October 2009 to February 2014. Forty-one patients were included in the study. RESULTS Complete resection was achieved in 40 patients (97.5%). A complete pathologic response was seen in 10 patients (24.4%). Mean hospital stay was 17.7 days (ranged 5-129 days). Early (in-hospital) mortality occurred in 2.4% (one patient after bilobectomy), late (six months) mortality in 4.9% (two patients after right pneumonectomy and bilobectomy), and overall morbidity in 58.5% (24 patients). Postoperative complications included: bronchopleural fistula (BPF) with empyema - three patients, empyema without BPF - five patients, air leak - eight patients, atrial fibrillation - eight patients, pneumonia - eight patients, and lobar atelectasis - four patients. CONCLUSION Following neoadjuvant therapy for stage IIIA NSCLC, pneumonectomy can be performed with low early and late mortality (0% and 5.8%, respectively), bilobectomy is a high risk operation (16.7% early and 16.7% late mortality); and lobectomy a low risk operation (0% early and late mortality). The need for major pulmonary resections should not be a reason to exclude patients from a potentially curative procedure if it can be performed with acceptable morbidity and mortality rates at an experienced medical centre.

Cervical Mediastinoscopic Lymphadenectomy for Accurate Staging in Lung Cancer

Accurate preoperative staging of the mediastinum is important in the treatment of non-small-cell lung cancer. Enlarged mediastinal lymph nodes on chest computed tomography are positive for malignancy on mediastinoscopy in only half of these patients. After negative mediastinoscopy, some positive nodes are found at thoracotomy. The aim of this study was to attempt to remove all lymph nodes accessible by cervical mediastinoscopic lymphadenectomy and reevaluate the same mediastinal stations at thoracotomy for missed lymph nodes. Between 1999 and 2003, 30 patients with operable non-small-cell lung cancer and enlarged mediastinal lymph nodes (>1 cm in diameter on computed tomography) that were negative on cervical mediastinoscopy underwent pulmonary resection with complete lymph node dissection. The total number of lymph nodes dissected in these 30 patients was 329 (143 at mediastinoscopy and 186 at thoracotomy); the mean numbers of nodes dissected were 4.8 at mediastinoscopy and 6.2 at thoracotomy. Ten (6.5%) residual lymph nodes were detected at thoracotomy in mediastinal stations R4, L4, and 7. The low number of missed lymph nodes demonstrates the accuracy of the technique of cervical mediastinoscopic lymphadenectomy.