Pressure pulsations enhance penetration index in COPD.

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved.

Non-invasive early detection of malignant pulmonary nodules by FISH-based sputum test.

BACKGROUND: Early detection decreases lung cancer mortality. The Target-FISH Lung Cancer Detection (LCD) Test is a non-invasive test designed to detect chromosomal changes (deletion or amplification) via Fluorescence in situ Hybridization (FISH) in sputum specimens from persons suspected of having lung cancer. We evaluated the performance of the LCD test in patients with highly suspicious pulmonary nodules who were scheduled for a biopsy procedure. METHODS: Induced sputum was collected from patients who were scheduled for biopsy of a solitary pulmonary nodule (0.8-3 cm) in one of 6 tertiary medical centers in the US and Israel. The lung cancer detection (LCD) Test combined sputum cytology and Target-FISH analysis on the same target cells and the results were compared to the pathology. Participants with non-surgical negative biopsy results were followed for 2 years to determine their final diagnosis. RESULTS: Of the 173 participants who were evaluated, 112 were available for analysis. Overall, the LCD test had a sensitivity of 85.5% (95% CI, 76.1-92.3), specificity of 69% (95% CI, 49.2-84.7) and an accuracy of 81.3% (95% CI, 72.8-88). The positive and negative predictive values (PPV, NPV) were 88.8% and 62.5%, respectively. The LCD test was positive in 9 of 11 lung cancer patients who had an initial negative biopsy. CONCLUSIONS: In a cohort of patients with highly suspicious lung nodules, the LCD test is a non-invasive option with good sensitivity and a high positive predictive value. A positive LCD test reinforces the need to aggressively pursue a definitive diagnosis of suspicious nodules.

Disease Management plus Recommended Care versus Recommended Care Alone for Ambulatory Patients with Chronic Obstructive Pulmonary Disease.

Rationale: The efficacy of disease management programs in the treatment of patients with chronic obstructive pulmonary disease (COPD) remains uncertain.Objectives: To study the effect of disease management (DM) added to recommended care (RC) in ambulatory patients with COPD.Measurements and Main Results: In this trial, 1,202 patients with COPD (age, ≥40 yr), with moderate to very severe airflow limitation were randomly assigned either to DM plus RC (study intervention) or to RC alone (control intervention). RC included follow-up by pulmonologists, inhaled long-acting bronchodilators and corticosteroids, smoking cessation intervention, nutritional advice and psychosocial support when indicated, and supervised physical activity sessions. DM, delivered by trained nurses during patients' visits to the designated COPD centers and by remote contacts with the patients between these visits, included patient self-care education, monitoring patients' symptoms and adherence to treatment, provision of advice in case of acute disease exacerbation, and coordination of care vis-à-vis other healthcare providers. The primary composite endpoint was first hospital admission for respiratory symptoms or death from any cause. During 3,537 patient-years, 284 patients (47.2%) in the control group and 264 (44.0%) in the study intervention group had a primary endpoint event. The median (range) time elapsed until a primary endpoint event was 1.0 (0-4.0) years among patients assigned to the study intervention and 1.1 (0-4.1) years among patients assigned to the control intervention; adjusted hazard ratio, 0.92 (95% confidence interval, 0.77-1.08).Conclusions: DM added to RC was not superior to RC alone in delaying first hospital admission or death among ambulatory patients with COPD.

Randomized controlled crossover trial of a new oscillatory device as add-on therapy for COPD.

A new oscillatory device administers predetermined pressure oscillation sequences into the chest cavity over inhaled/exhaled air streams at low positive pressure. We assessed device safety and effect on 6MW performance, pulmonary function, and health-related quality-of-life (HRQOL) in moderate-to-very severe COPD in a randomized, double-blind, controlled, crossover study. Outcomes with an oscillatory device (Pulsehaler(TM), Respinova Ltd, Herzliya, Israel) and a "muted" sham device (control) of identical appearance that delivered continuous positive air pressure were compared in two groups receiving opposite treatment sequences: 2-week oscillatory device/control, 2-week washout, 2-week control/oscillatory device, 2-week washout. The clinical trial was registered ( www.clinicaltrials.gov , NCT00821418) and approved by the Hadassah-Hebrew University Medical Center Institutional Review Board (08-608). All participants signed informed consent; 22 patients completed the study with no marked differences in COPD exacerbations or side effects. A total of 91% of patients treated with the oscillatory device had a clinically significant improvement (increase >40 m) in 6MW performance. The 6MW distance with the oscillatory device increased significantly after 1 week of treatment (51.6 ± 7.6 m, +13.5 ± 2.3%, p < 0.001), and more after 2 weeks (61.8 ± 9.0 m, 16.3 ± 2.7%, p < 0.001). This increase with the oscillatory device was significantly greater (p < 0.001) than the 15.4 ± 10.4 m increase (4.2 ± 2.6%, NS) with control. FVC and inspiratory capacity (IC) improved significantly (p = 0.03 for each) with the oscillatory device but not with control. HRQL improved markedly (≥1 point) for dyspnea and mastery with the oscillatory device (p = 0.02) but not control. Treatment with a new oscillatory device appears to be safe, and to improve 6MW performance, pulmonary function, and HRQL in COPD. Further evaluation is warranted.

[Myocarditis in Olympic marathon runner].

One thousand five hundred runners participated in the Tiberias marathon in 2010 and more than 35,000 runners participate annuaLly in large city marathons. Elite marathon runners train strenuously, tending to ignore various symptoms of pain, aches and mild respiratory infections, as they continue training relentlessly for the upcoming marathons. Intensive training may weaken the immune system, thus increasing the susceptibility for infection, mainly viral infections. We present a case study of an Olympic marathoner, an Ethiopian of Jewish origin, aged 41 who began training for an upcoming marathon on May 1, 2010. During the following 6 weeks he ran 180-240 km/week at easy to moderate paces. In mid-June he added 2 high intensity runs per week to his running schedule. During the first 3 weeks, quality running improvement was noted, but then the runner started to feel muscle pains in his thighs, shortness of breath and chest uneasiness while running fast. The physical examination conducted on 19/7/10 was normal. Examinations showed white blood cell (WBC) count was 2800, 55% lymphocytes, 11.8% monocytes, titers for recent CMV, Epstein Bar, enteroviruses, were negative. On 24/7/10 ECG showed inverted symmetric T-wave in precordial leads, chest X-ray, echocardiogram, troponin, and WBC were normal. Clinical features, WBC, and ECG findings, suggested myocarditis, probably viral The runner stopped running. On 9/9/10 ECG was normal. On 15/9/10 cardiac virtual catheterization was normal. Cardio-pulmonary exercise test on 4/10/2011 was normal. Thereupon, the athlete resumed running. This case stressed the fact that physicians should be alert to medical complaints from marathoners, in order to prevent serious outcomes from dissimulate runners. A literature search was conducted related to distance runners and high level orienteer's myocarditis causes and prevention.

National asthma observational survey of severe asthmatics in Israel: the no-air study.

BACKGROUND: Asthma is considered a global public health issue requiring a significant medical expenditure as a result of its high prevalence and the low rate of disease control. OBJECTIVE: This is the first nationwide survey of severe asthma patients carried out in Israel. In this study we aimed to assess health resources utilization, compliance with treatment and disease-control in a subgroup of patients with severe asthma in Israel. MATERIAL AND METHOD: One hundred and twenty-three patients with a diagnosis of asthma for more then one year, as well as a hospitalization during the last 12 months due to asthma exacerbation or maintenance systemic steroids therapy, were included in this non-interventional observational study. RESULTS: Asthma was uncontrolled in 43.9%, partly controlled in 50.4% and well controlled in only 5.7%. The majority of the patients (83%) were compliant with drug treatment. CONCLUSION: The fact that 83% of the asthma patients included in this study were compliant with their asthma therapy was not manifested in asthma control. Therefore concrete tools are required for achieving and maintaining asthma control, especially in the treatment of the most severe asthmatic patients.

Organizing pneumonia and non-necrotizing granulomata on transbronchial biopsy: coexistence or bronchiolitis obliterans organizing pneumonia secondary to Mycobacterium kansasii disease.

Mycobacterium kansasii disease was diagnosed in an 85-year-old woman admitted to the hospital for cough and gradually worsening breathlessness. Transbronchial biopsy indicated either non-necrotizing granulomata or bronchiolitis obliterans organizing pneumonia (BOOP). She was cured with combined therapy of specific anti-mycobacterial medications and systemic steroids. To our knowledge, this is the first report of M. kansasii non-tuberculous mycobacterium disease with a BOOP-like pattern on lung biopsy.

Greater weight loss and hormonal changes after 6 months diet with carbohydrates eaten mostly at dinner.

This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner) or control weight loss diets for 6 months. On day 0, 7, 90, and 180 blood samples and hunger scores were collected every 4 h from 0800 to 2000 hours. Anthropometric measurements were collected throughout the study. Greater weight loss, abdominal circumference, and body fat mass reductions were observed in the experimental diet in comparison to controls. Hunger scores were lower and greater improvements in fasting glucose, average daily insulin concentrations, and homeostasis model assessment for insulin resistance (HOMA(IR)), T-cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were observed in comparison to controls. The experimental diet modified daily leptin and adiponectin concentrations compared to those observed at baseline and to a control diet. A simple dietary manipulation of carbohydrate distribution appears to have additional benefits when compared to a conventional weight loss diet in individuals suffering from obesity. It might also be beneficial for individuals suffering from insulin resistance and the metabolic syndrome. Further research is required to confirm and clarify the mechanisms by which this relatively simple diet approach enhances satiety, leads to better anthropometric outcomes, and achieves improved metabolic response, compared to a more conventional dietary approach.

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.

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.

Lung function and cardiopulmonary exercise capacity in patients with corrected tetralogy of Fallot.

BACKGROUND: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead active lives and have no subjective exercise limitation. OBJECTIVES: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF. METHODS: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure. RESULTS: Fifty consecutive patients (33 men, 17 women) aged 29 +/- 11 years who underwent surgical repair of TOF at age 10.1 +/- 10.9 years were enrolled. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75-78% predicted. CONCLUSIONS: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.

Efficacy of nebulized fluticasone propionate in adult patients admitted to the emergency department due to bronchial asthma attack.

BACKGROUND: Locally delivered steroids by inhalers or nebulizers have been shown in small trials to be effective in acute asthma attack, but evidence-based data are insufficient to establish their place as routine management of adult asthma attacks. OBJECTIVES: To determine the efficacy of nebulized compared to systemic steroids in adult asthmatics admitted to the emergency department following an acute attack. METHODS: Adult asthmatics admitted to the ED were assigned in random consecutive case fashion to one of three protocol groups: group 1--nebulized steroid fluticasone (Flixotide Nebules), group 2--intravenous methylprednisolone, group 3--combined treatment by both routes. Objective and subjective parameters, such as peak expiratory flow, oxygen saturation, heart rate and dyspnea score, were registered before and 2 hours after ED treatment was initiated. Steroids were continued for 1 week following the ED visit according to the protocol arm. Data on hospital admission/discharge rate, ED readmissions in the week after enrollment and other major events related to asthma were registered. RESULTS: Altogether, 73 adult asthmatics were assigned to receive treatment: 24 patients in group 1, 23 in group 2 and 26 in group 3. Mean age was 44.4 +/- 16.8 years (range 17-75 years). Peak expiratory flow and dyspnea score significantly improved in group 1 patients compared with patients in the other groups after 2 hours of ED treatment (P = 0.021 and 0.009, respectively). The discharge rate after ED treatment was significantly higher in groups 1 and 3 than in group 2 (P = 0.05). All 73 patients were alive a week after enrollment. Five patients (20.8%) in the Flixotide treatment arm were hospitalized and required additional systemic steroids. Multivariate analysis of factors affecting hospitalization rate demonstrated that severity of asthma (odds ratio 8.11) and group 2 (OD 4.17) had a negative effect, whereas adherence to chronic anti-asthma therapy (OD 0.49) reduced the hospitalization rate. CONCLUSIONS: Our study cohort showed the advantage of nebulized steroid fluticasone versus systemic corticosteroids in adult asthmatics managed in the ED following an acute attack. Both these and previous results suggest that nebulized steroids should be used, either alone or in combination with systemic steroids, to treat adults suffering acute asthma attack.

Asthma control and compliance in a cohort of adult asthmatics: first survey in Israel.

BACKGROUND: Asthma control and treatment compliance are widely investigated issues around the world. Studies have demonstrated relatively low asthma compliance and control in 40-90% of asthma patients in different countries. There are no available data on the Israeli adult asthmatic population OBJECTIVES: To investigate the level of asthma control and compliance in adult asthmatic patients. METHODS: This cross-sectional study of consecutive adult asthmatic patients visiting the pulmonary clinic used a combined questionnaire that included demographics, data on asthma severity and management, and asthma control and compliance scores. Each patient was interviewed and questionnaires were filled out during a routine visit. RESULTS: The study group comprised 142 males (35.4%) and 259 females (64.6%). Compliance was found optimal in 8 patients (2%), fair in 146 (36%), partial in 156 (39%) and poor in 92 (23%) of the participating asthmatic patients. Asthma control was found optimal in 26 (7%), fair in 124 (31%), partial in 122 (30%) and poor in 129 (32%). Sephardic and Ashkenazi Jewish origin, higher level of education, and treatment protocol including either single fixed-dose inhalers or short-acting beta-agonist bronchodilators significantly improved compliance in our cohort. Socioeconomic status and compliance were found to positively affect asthma control, whereas active smoking negatively affected asthma control in the study patients. CONCLUSIONS: The figures of optimal asthma control and compliance to treatment in Israeli adult asthmatics are low and worse than reported in other studies abroad.

Assessment of functional capacity in patients with chronic obstructive pulmonary disease: correlation between cardiopulmonary exercise, 6 minute walk and 15 step exercise oximetry test.

BACKGROUND: Different exercise tests are used to evaluate the functional capacity in chronic obstructive pulmonary disease. The cardiopulmonary exercise test is considered the gold standard, but the 6 minute walk and the 15 step exercise oximetry test are considerably less expensive. OBJECTIVES: To determine whether reliable data could be obtained at lower cost. METHODS: The study sample consisted of 50 patients with mild to severe stable COPD. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated. RESULTS: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 +/- 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64). CONCLUSIONS: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Is routine chest radiography after transbronchial biopsy necessary?: A prospective study of 350 cases.

BACKGROUND AND STUDY OBJECTIVE: Pneumothorax following flexible bronchoscopy (FB) with transbronchial biopsy (TBB) occurs in 1 to 6% of cases. Routine chest radiography (CXR) following TBB is therefore requested by most pulmonologists in an attempt to detect complications, particularly pneumothorax. The objective of this study was to determine if routine CXR after bronchoscopy and TBB is necessary. PATIENTS AND METHOD: The study group included 350 consecutive patients who underwent FB with TBB at our institution between December 2001 and January 2004. Routine CXR was performed up to 2 h after the procedure in all cases. Additionally, the following information was recorded in all patients: sex, age, immune status, indication for bronchoscopy, total number of biopsies done, segment sampled, pulse oxygen saturation, and development of symptoms suggestive of pneumothorax. RESULTS: Pneumothorax was diagnosed radiologically in 10 patients (2.9%). Seven patients had symptoms strongly suggestive of pneumothorax prior to CXR, including four patients with large (> 10%) pneumothorax. The other three patients were asymptomatic, with only minimal pneumothorax (

Recurrence of pulmonary veno-occlusive disease after heart-lung transplantation.

Pulmonary veno-occlusive disease, a rare cause of pulmonary hypertension, is characterized by extensive and diffuse occlusion of pulmonary veins by fibrous tissue. Although the diagnosis can be suspected by the presence of the classic clinical triad of severe pulmonary arterial hypertension, radiographic evidence of pulmonary hypertension and edema, and normal pulmonary artery occlusion pressure, the definitive diagnosis is histopathologic. The prognosis of pulmonary veno-occlusive disease is poor with most described patients dying within 2 years of diagnosis. Although anti-coagulation, oxygen, and vasodilator therapies are effective temporarily, the definitive treatment is lung transplantation. We describe the recurrence of pulmonary veno-occlusive disease at 3 months after heart-lung transplantation in a 26-year-old man. Recurrence after transplantation for this disease has not been reported previously, and lung transplantation was thought to be definitive treatment. With this 1st report of early recurrence of pulmonary veno-occlusive disease after heart-lung transplantation, we believe that extrapulmonary factors may play a role in the pathogenesis of this rare disease.

Interactions between nitric oxide and arachidonic acid in lung epithelial cells: possible roles for peroxynitrite and superoxide.

This study investigated interactions between nitric oxide synthesis and phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation, inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release were determined following treatment with: (1) the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2) arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2 inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5) the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3 inhibited nitrite formation and inducible nitric oxide synthase expression in a dose-dependent manner; (3) SIN-1, together with AA release agonists, significantly increased the AA output, and (4) trolox counteracted the SIN-1 effects. Our results demonstrate cross talk between nitric oxide synthase and PLA(2) pathways, with a possible intermediary role for peroxynitrite and superoxide.

[Lung and heart-lung transplantation in Rabin medical center: early experience with 70 cases].

Lung transplantation is a relatively new field in solid organ transplantation. We present our early experience with the first 70 cases at the Rabin Medical Center during the years 1997-2003. Forty seven patients underwent single lung, eight double lung and eight heart-lung transplantations. The patients treated included 49 men and 21 women aged 5-66 years. There were 26 cases with emphysema COPD. 30 patients with pulmonary fibrosis. 5 patients with pulmonary hypertension/Eisenmenger and 9 patients with cystic fibrosis and bronchiectasis. Although early results (1997-1999) showed 1 and 3 year survival of only 50%, in the last 3 years (2000-2003), survival reached 84% and 82% at 1 and 3 years respectively. Improvement in the success rate is due to better patient selection, new immunosuppressive regimen and, most importantly, excellent teamwork. We conclude that lung transplantation is a viable option for selected patients with end-stage lung disease.