Basiliximab as an alternative to antithymocyte globulin for early immunosuppression in lung transplantation.

OBJECTIVE: Basiliximab (BAS), an interleukin-2 monoclonal antibody, has shown promising results as induction therapy in liver and kidney transplantation. We compared the efficacy and patient tolerability of BAS and antithymocyte globulin (ATG) in lung transplantation (LTx). PATIENTS AND METHODS: The study included 37 patients in two groups (ATG and BAS, respectively). The indication for LTx was emphysema in 62.6% of patients in group 1 and 57.1% of patients in group 2. Mean (SD) patient characteristics compared in the two groups included age (52.0 [9.8] vs 54 [10.6] years), height (172.0 [10.1] vs 169 [7.55] cm), and weight (73.9 [15.3] vs 64.4 [14.2] kg) (P = .049). Induction therapy after LTx in the two groups was as follows: in 16 transplantation procedures (eight single and eight bilateral) performed between April 1998 and December 2002, ATG, 3 mg/kg/d for 3 days, was administered, and in 21 transplantation procedures (15 single and 6 bilateral) performed between January 2003 and July 2005, BAS, 20 mg on days 0 and 4, was given. Dosages of cyclosporine, azathioprine, and steroids for maintenance therapy were equivalent in the two groups. We retrospectively compared patient tolerability, occurrence of acute rejection or infection (from bacteria, cytomegalovirus [CMV], or Aspergillus), and outcomes between the two groups during 2 years of follow-up. RESULTS: No cytokine-mediated reaction was observed in either group; however, there was a difference in hematologic effects. On day 2, mean (SD) platelet count was significantly lower in the ATG group at 113,500 (56,400)/mm(3) vs 151,900 (57,300)/mm(3) (P = .046). Because of severe thrombocytopenia, three patients could not be given ATG on day 3. The overall incidence of aspergillosis (18.8% vs 19.0%) and CMV infection (31% vs 57%) was similar in the two groups. However, when the recipient was CMV-positive and the donor was CMV-negative, the there was a clear trend (33.3% vs 88.9%). The number of acute rejection episodes was similar (43.8% vs 52.4%). Survival increased by 20% in the BAS group (P = .03). CONCLUSION: In LTx, safety of BAS use is as good as or better than that of ATG, with no difference in acute rejection episodes or infections, with the possible exception of increased reactivation of CMV infection. Thus, BAS could be an alternative to ATG as induction therapy in LTx; however, further studies are necessary.

Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study.

A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.

Does negative expiratory pressure (NEP) during spontaneous breathing predict respiratory impairment in elderly?

OBJECTIVE: The purpose of this study is to assess whether expiratory flow limitation (FL), as measured by applying a negative pressure at the mouth during tidal expiration, can evaluate the respiratory impairment in elderly patients. METHODS: The study was carried out in 67 consecutive elderly inpatients (24 men and 43 women). Negative expiratory pressure (NEP) of -5 (NEP 5) and -10 (NEP 10) cm H2O were applied during spontaneous tidal expiration. According to the results of the NEP technique, the patients were stratified in two categories: not flow limited and flow limited. We realized then classic forced expiratory manoeuvres (FEV1, FVC) and clinical evaluation of dyspnea (NYHA). According to the values of the lung function data, elderly patients were then divided in 3 groups (normal, obstructive, restrictive). RESULTS: The sensitivity, the specificity, the positive and negative predictive values for the diagnosis of obstructive syndrome by the presence of flow limitation during NEP 5 were 53, 74, 45, 79% respectively and 58, 83, 58, 83% respectively during NEP 10. These findings show that the correlation between FL obtained by the NEP technique during spontaneous breathing and spirometry is not very good despite the fact that both were well correlated with dyspnea score. CONCLUSIONS: In clinical practice, faced with an elderly dyspneic patient unable to perform maximal expiratory manoeuvres, the evaluation of flow limitation by NEP technique seems nor to be reliable to predict an obstructive functional impairment nor to be able to explain the origin of his dyspnea.

Noninvasive prediction of pulmonary hypertension in chronic obstructive pulmonary disease by Doppler echocardiography.

Thirty-six patients with chronic obstructive pulmonary disease (COPD) were studied by pulsed Doppler echocardiography. In 32 of the 36 patients, adequate Doppler signals were obtained in the pulmonary arterial trunk and correlated with right cardiac hemodynamics. The studied group included 26 patients with mean pulmonary arterial pressure (MPAP) greater than 20 mm Hg at rest (group A, with pulmonary hypertension) and six patients with MPAP of 20 mm Hg or less (group B, without pulmonary hypertension). A control group (group C) consisted of 12 subjects with normal hemodynamic data and pulmonary function. Analysis of Doppler data included flow velocity curve pattern, presence of a negative presystolic velocity, right ventricular pre-ejection period (RVPEP) and ejection period (RVEP), time between onset and peak of pulmonary velocity (time to peak velocity, TPV) and derived ratios of TPV/RVPEP and TPV/RVEP. In patients with pulmonary hypertension, the Doppler flow velocity curve in the pulmonary trunk showed a rapid acceleration and an early deceleration. The mean value for TPV was 78 +/- 12 msec in group A, 115 +/- 11 msec in group B, and 127 +/- 10 msec in group C. In patients with COPD, significant correlations were observed between TPV and log10 MPAP (r = -0.77; SEE = 0.07) and between TPV and log10 total pulmonary resistances (r = -0.84; SEE = 0.05). Accordingly, pulsed Doppler echocardiography may be a useful tool to predict pulmonary hypertension due to chronic pulmonary disease.

Relationship between inflammatory processes and gas exchanges in pulmonary sarcoidosis.

In the present study, we investigated whether the analysis of cells and proteins collected by bronchoalveolar lavage (BAL) could accurately reflect the degree of functional impairment in pulmonary sarcoidosis. Eighteen patients with biopsy-proven sarcoidosis were prospectively evaluated. An inverse relationship was demonstrated between BAL coefficient of excretion relative to albumin (RCE) values of IgG and IgA and diffusion for carbon monoxide (Dco). A similar negative correlation existed with PaO2 at the end of a maximal exercise. Steroid therapy in five patients lowered concomitantly BAL RCE of IgA and IgG while Dco values increased. Immunoperoxidase studies in three lung biopsies revealed numerous Ig-containing cells within the lung parenchyma. We suggest that these BAL Ig values reflected the mononuclear cell infiltration of the bronchiolovascular sheaths and lung interstitium. This cellular infiltration likely induces a distortion of the capillary bed and may affect the gas exchanges in a reversible way.

Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis.

STUDY OBJECTIVE: To assess the frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in patients with allergic bronchopulmonary aspergillosis (ABPA). DESIGN: Case-control study. All subjects in the study were screened for the presence of 13 mutations in the CFTR gene (R117H, 621 + 1G(-)>T, R334 W, Delta F508, Delta I507, 1717-1G(-)>A, G542X, R553X, G551D, R1162X, 3849 + 10kbC(-)>T, W1282X, and N1303K). Moreover, they were also screened for the presence of the 5T variant in intron 8. SETTING: University hospital and community-based hospital. PATIENTS: Twenty-one white patients with ABPA participated in the study. The presence of CFTR mutations was also investigated in 43 white subjects with allergic asthma who did not show sensitization to Aspergillus fumigatus and in 142 subjects seeking genetic counseling for diseases other than cystic fibrosis (CF). RESULTS: Six patients with ABPA were found to be heterozygous for one CFTR mutation, including Delta F508 (n = 2), G542X (n = 1), R1162X (n = 1), 1717-1G(-)>A (n = 1), and R117H (n = 1). The 5T allele was not detected in ABPA patients. None of the ABPA patients showed sweat chloride concentrations > 60 mEq/L. The frequency of CFTR mutation carriers was significantly higher in ABPA patients (6 of 21 patients; 28.5%) than in control asthmatic subjects (2 of 43 subjects; 4.6%; p = 0.01) and in subjects seeking genetic counseling (6 of 142 subjects; p < 0.001). CONCLUSION: These findings indicate that in patients without a clinical diagnosis of CF, CFTR gene mutations could be involved in the development of ABPA, in association with other genetic or environmental factors.

Tracheal dead space influences regional ventilation measurement in dogs.

The lung volume at which airway closure begins during expiration (closing volume, CV) can be measured 1) with a radioactive bolus inspired at residual volume (RV) and 2) with the single-breath N2 elimination test. In previous studies in dogs, we observed that N2 CV was systematically larger than 133Xe bolus CV (Xe CV) [N2 CV %vital capacity (VC) = 35 +/- 2.3 (SE) vs. Xe CV %VC = 24 +/- 2.2, P less than 0.01]. Because the regional RV in the dog is evenly distributed throughout the lung and all airways closed at RV, N2 CV is related to the regional distribution of the tracheal N2; differences between N2 and Xe CV could then be related to the size of the inhaled dead space. Simultaneous measurements of Xe and N2 CV were performed at various sites of Xe bolus injection while the regional distribution of the bolus was measured. Injections at the level of the carina increased Xe CV to a value (30 +/- 1.4%VC) near simultaneous N2 CV (32 +/- 1.5%VC) and increased the unevenness of regional distribution of the Xe bolus. The difference between N2 and Xe CV is then the result of the size of the inspired tracheal dead space. Moreover, comparisons between different values of Xe CV require injections of the boluses at the same distance from the carina.

Thoracoscopic resection of pulmonary nodules after computed tomographic-guided coil labeling.

BACKGROUND: A limiting factor in performing video-assisted thoracic surgery for resection of peripheral solitary pulmonary nodules has been the recognition of the lesion visually. This study reports our clinical experience of injecting a small metallic marker under computed tomographic scan guidance before the operation, allowing localization of the lesion. METHODS: A series of 14 patients underwent video-assisted thoracic surgery for removal of 15 pulmonary nodules situated in the outer third of the lung. Before operation, a radiopaque microcoil was injected just behind the lesion and then used to locate, under fluoroscopy, the area to be resected during thoracoscopy. The technique was evaluated for accuracy, reliability, and ease of use. RESULTS: Microcoil labeling of peripheral pulmonary nodules allowed in every case a complete resection and a histologic identification of the lesion. It is more stable and accurate than methylene blue dye marking, and it is as easy to perform as computed tomographic scan-guided biopsy. The incidence of complication was small in spite of our inexperience with the technique. CONCLUSIONS: Our experience with microcoil injection shows that it provides consistent and highly accurate marking of pulmonary nodules for video-assisted thoracic surgery, allowing secure resection with a safe margin.

Does inspiratory behaviour affect the efficiency of non-invasive ventilation in COPD patients?

Non-invasive ventilation (NIV) is more and more used. Some failures of the technique have been reported, and efforts are needed to understand them. Collaboration (inspiratory behaviour) of the patient during NIV could play a role in the success of this technique. We have studied the influence of this one on the efficiency of NIV. While ventilating 10 stable chronic obstructive pulmonary disease patients with a nasal pressure support ventilation (PSV), we measured their flow and volume with a pneumotachograph and oesophageal and gastric pressures during three different respiratory voluntary behaviours: relaxed inspiration, active inspiratory effort and resisted inspiration. We showed that when compared with the relaxed inspiration: (a) Active inspiratory effort increases slightly minute ventilation from 14.8 +/- 4.7 to 15.41 +/- 4.19 during PSV 10/0 without change of breathing frequency but with an important increase of inspiratory work (W(OB)) from 14.47 +/- 9.43 to 28.55 +/- 25.35 J/min (P=0.008). PEEPi increases with active behaviour during PSV but not during BiPAP. (b) A resisted inspiration decreases inspiratory work (to 7.53 +/- 8.6 J/min) at the price of a decrease of the minute ventilation to 11.47 +/- 4.20 l/min (P=0.06). Results of ventilation, PEEPi and work parameters were identical during the bilevel pressure support (15/5 cm H2O). The aims of NIV being to increase ventilation and unload the inspiratory muscles, our results suggest that during NIV, a relaxed spontaneous breathing is preferable. These differences between the inspiratory behaviours could affect the expected benefits of PSV in acutely ill patients.

Breathing frequency and use of expiratory muscles do influence the dynamic positive end-expiratory pressure.

End-expiratory air trapping due to obstructive airway disease can be estimated through the measurement of intrinsic positive end-expiratory pressure PEEPi. The influence of breathing-frequency and use of expiratory muscles on PEEPi were measured in 10 normal and 10 chronic bronchitic patients (COPD). Insignificant control values of PEEPi increased to measurable values at high breathing rate in normal subjects. Control values were higher in COPD patients and increased at fast breathing rate. When corrected for the use of expiratory muscles according to simultaneous gastric pressure drop, PEEPi decreased in COPD, but still increased at high rate. We conclude that modifying the respiratory rate can increase PEEPi values independently of the severity of airway obstruction and the use of expiratory muscles. Before estimating the pathological value of a PEEPi measurement or evaluating the effects of a treatment, we always need to know the simultaneous breathing frequency.

Is a lung perfusion scan obtained by using single photon emission computed tomography able to improve the radionuclide diagnosis of pulmonary embolism?

Planar pulmonary scintigraphy is still regularly performed for the evaluation of pulmonary embolism (PE). However, only about 50-80% of cases can be resolved by this approach. This study evaluates the ability of tomographic acquisition (single photon emission computed tomography, SPECT) of the perfusion scan to improve the radionuclide diagnosis of PE. One hundred and fourteen consecutive patients with a suspicion of PE underwent planar and SPECT lung perfusion scans as well as planar ventilation scans. The final diagnosis was obtained by using an algorithm, including D-dimer measurement, leg ultrasonography, a V/Q scan and chest spiral computed tomography, as well as the patient outcome. A planar perfusion scan was considered positive for PE in the presence of one or more wedge shaped defect, while SPECT was considered positive with one or more wedge shaped defect with sharp borders, three-plane visualization, whatever the photopenia. A definite diagnosis was achieved in 70 patients. After exclusion of four 'non-diagnostic' SPECT images, the prevalence of PE was 23% (n =15). Intraobserver and interobserver reproducibilities were 91%/94% and 79%/88% for planar/SPECT images, respectively. The sensitivities for PE diagnosis were similar for planar and SPECT perfusion scans (80%), whereas SPECT had a higher specificity (96% vs 78%; P =0.01). SPECT correctly classified 8/9 intermediate and 31/32 low probability V/Q scans as negative. It is concluded that lung perfusion SPECT is readily performed and reproducible. A negative study eliminates the need for a combined V/Q study and most of the 'non-diagnostic' V/Q probabilities can be solved with a perfusion image obtained by using tomography.

Non-invasive positive pressure ventilation for exacerbation of chronic obstructive pulmonary patients in the emergency department.

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly present to the emergency department for treatment. Some of them, despite appropriate therapy become more dyspnoeic with increasing acute respiratory failure. The requirement for intubation and mechanical ventilation is for these patients often associated with a prolonged and complicated intensive care unit stay and has been associated with morbidity and mortality rates in excess. Non-invasive ventilation (NIV) emerged recently as a means of reducing those complications. NIV can be a safe and effective means of augmenting ventilation and decreasing inspiratory work in many patients with acute exacerbation of COPD. NIV is generally started in the intensive care unit. Except for a few negative studies, the overall compending studies seem to be in favour of the utilization of NIV in cases of exacerbation of COPD patients. There are few published data on the question whether NIV could or should be started earlier and initiated in the emergency department. It seems that NIV treatment could be an effective addition to standard treatment especially for acute exacerbation of COPD. A more extensive and routine use of non-invasive ventilation in the emergency department requires further study.

Survey of non-invasive ventilation for acute exacerbation of chronic obstructive pulmonary disease patients in emergency departments in Belgium.

A study was undertaken to assess the availability and use of non-invasive ventilation (NIV) for the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) in emergency departments in Belgium. A questionnaire was sent to the head physicians of 145 emergency departments (EDs) found in the list of the Belgian College of Emergency Physicians (BeCEP). Ninety eight questionnaires were analysed (representing 68% of the questionnaires sent). NIV was used in 49% of the EDs. In the hospitals where NIV was not used, the most important reasons given were no available equipment in 71%, lack of experience with this form of treatment in 32.7%, and more time consuming for physicians and nursing staff in 22.8%. Only 3.8% of the physicians doubted the benefit of NIV treatment. In the hospitals where NIV was used, the patient was watched during the first hour by one nurse only in 19.6%, by one physician in 8.6% and by a nurse and a physician in 54.5%. NIV was used for more than 4 h in 33% of EDs. Pressure-controlled ventilation (with home respirators) was used more often than volume-controlled ventilation.

[Pneumatosis cystoides intestinalis associated with Steinert disease]. / Pneumatose kystique intestinale associée à une maladie de Steinert.

We report the case of a 63-year-old patient suffering from myotonic dystrophy, complicated with respiratory insufficiency, who presented a pneumoperitoneum without sign of peritonitis. Diagnosis of pneumatosis cystoides coli was based on CT scan evidence. Given oxygenotherapy and antibiotherapy, the patient rapidly improved. The association between the two affections has, to our knowledge, not been previously described.

Medical thoracoscopy in the management of pneumothorax.

Medical thoracoscopy is an efficient technique to evaluate the gravity of a spontaneous pneumothorax in order to choose the most appropriate treatment. Classification of lesions into four types (from endoscopically normal lungs to large bullae) guides the choice from local talc pleurodesis to surgical bullectomy and pleurectomy. Most patients with the first three types can be treated with talc pleurodesis, with a good success rate (93%) and no functional sequelae (lung volumes within the normal range in primary pneumothorax and similar to previous values in secondary pneumothorax). Neuroleptanalgesia in association with patient-controlled analgesia appears to be superior to local anaesthesia in the prevention of immediate pain induced by talc poudrage. Talc pleurodesis is the treatment of choice for recurring spontaneous pneumothorax because of its high success rate and absence of complications.

[Manifestations, diagnosis and treatment of non-tuberculous mycobacterial infections in non-immunodepressed patients]. / Manifestations, diagnostics et traitements des mycobactérioses non tuberculeuses chez le sujet non immunodéprimé.

Non-tuberculous mycobacteria (NTM) can be the etiologic agents of chronic pulmonary disease, lymphadenitis, skin and soft-tissue infection and disseminated disease in non-immunocompromised patients. The recognition of disease needs repeated isolation of the NTM from bronchopulmonary secretions or from tissue biopsies, and its identification by specific laboratory methods. A wide spectrum of clinical presentations and severity of disease can be found, from spontaneous healing to progressive and destructive lung disease, and death, according to predisposing conditions and mycobacterial species. The choice of surgical and drug treatment will depend on identification of specific pathogen and clinical evaluation.

[Spontaneous pneumothorax. Results of pleural talc therapy using thoracoscopy]. / Pneumothorax spontané. Résultats du talcage pleural sous thoracoscopie.

The aim of this retrospective study is to evaluate the advantage of thoracoscopy and the efficacy of talcage in the treatment of spontaneous pneumothorax (SP). Two hundred cases have been analyzed with a follow-up of 1 to 8 years after the occurrence of the disorder. The ratio man/woman is 4/1. One hundred and forty two pneumothorax are considered as being of idiopathic origin and 58 are associated to bronchopneumopathy, with a mean age of 33 and 56 years, respectively. The percentage of smokers is 69.5% with a mean smoking of 14 packets/years. The endoscopic aspect of pleura is either normal (30%) or shows adhesions (23.5%), blebs (17%) or bullaes (29.5%). Thoracoscopy allowed talc poudrage in 191 patients and allowed to indicate the need for surgery in nine patients. The immediate success rate of talcage is 93.7%. In the group of immediate failure (6.3%), unexpected bullous structures (8/12) are found at tomodensitometry (TDM), as well as during surgery. Late recurrence is reported in 2 cases (1%) at 20 and 25 months. Radiological sequelaes are minimum (9%). Lung function testing in patients with idiopathic pneumothorax (n = 64) shows, before talc poudrage, signs of pulmonary hyperdistension (total lung capacity (TLC) at 116% of predicted values), reflecting the illness pathology, 3 months after talcage a discrete restrictive syndrome (TLC 93%) and one year after the partial recovery of the lost volume (TLC 105%). Tomodensitometry revealed to be complementary to thoracoscopy in secondary SP and very instructive in idiopathic SP after immediate failure of talc poudrage.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemoptysis]. / Hémoptysies.

An 82 years-old man is admitted for suspicion of bronchial cancer. He has a persistent cough, repeated bronchial infections and haemoptysis. On thoracic CT-scan, there is an increased thickness of the bronchial walls situated at the tracheobronchial cross.

Correlations between cyclosporine concentrations at 2 hours post-dose and trough levels with functional outcomes in de novo lung transplant recipients.

BACKGROUND: Although the reliability of cyclosporine (CyA) concentration at 2 (C2) hours postdosing has been established for kidney, liver, and heart transplant recipients, its use in lung cases remains to be validated. We investigated the relationship between CyA dual time point monitoring and long-term functional outcomes after lung transplantation. METHODS: We included data from 38 lung transplant recipients receiving CyA, azathioprins, and steroids in the study. CyA dosages were based on the trough concentrations. CyA concentrations at 0 (C0) and 2 (C2) hours postdosing were obtained at 1, 2, 3, 6, 9, 12, 15, 18, and 24 months postoperative. We retrospectively compared average CyA level (C0 and C2) during the first 3 posttransplantation months with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow 25%-75 % (FEF 25-75), creatinine, systolic blood pressure (SBP), and diastolic blood pressure (DBP) using regression analysis via generalized estimating equations (GEE). RESULTS: Only improvement in FVC (P = .033) and deterioration of SBP (P < .001) were related to C0 monitoring. No correlation was observed between C0 and FEV1 (P = .13), FEF 25-75 (P = .48), creatinine (P = .07), and DBP (P = .97). Nor was any relationship observed between C2 concentrations and FEV1 (P = .64), FVC (P = .38), FEF 25-75 (P = .09), creatinine (P = .95), SBP (P = .73), or DBP (P = .51). CONCLUSION: There was a lack of a relationship between CyA concentrations (C0 and C2) and functional outcomes among de novo lung transplantations except for a positive correlation of 0 value with long-term improved FVC and increased SBP. This study suggested that C2 determinations may not improving lung recipient management.