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.

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.

Necrotising sarcoid granulomatosis: clinical, functional, endoscopical and radiographical evaluations.

Necrotising sarcoid granulomatosis (NSG) is a rare disease diagnosed on the basis of pathological features. The present study reports the characteristics of 14 cases of NSG. The mean age at the appearance of first symptoms was 37 yrs and the mean delay between first symptoms and diagnosis was 1 yr. Extrarespiratory symptoms were more common (12 out of 14) than respiratory symptoms (eight out of 14). Seven patients had inflammatory syndrome. Bronchoalveolar lavage was performed in eight patients and found to be normal in three cases. Respiratory function was normal in 13 patients, but carbon monoxide diffusing capacity was slightly decreased in eight of the 11 patients tested. A computed tomography scan showed a solitary nodule in four out of 14 cases, bilateral nodules in three and infiltrates in seven. One patient died from neurological complications despite treatment with corticosteroids and immunosuppressive drugs. Two cases of relapse were observed in patients initially treated with corticosteroids, and there were two cases of relapse after surgery. No relapse occurred in the five untreated patients. During the follow-up, lung cancer was detected at 26 months and 8 yrs, respectively, after NSG diagnosis in two patients. In conclusion, no one treatment is associated with a better outcome than the others, although lung biopsy might be necessary in case of isolated nodule or cavitation. Greater vigilance is required during the follow-up.

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.

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.

Talcage by medical thoracoscopy for primary spontaneous pneumothorax is more cost-effective than drainage: a randomised study.

Simple thoracoscopic talcage (TT) is a safe and effective treatment of primary spontaneous pneumothorax (PSP). However, its efficacy has not previously been estimated in comparison with standard conservative therapy (pleural drainage (PD)). In this prospective randomised comparison of two well-established procedures of treating PSP requiring at least a chest tube, cost-effectiveness, safety and pain control was evaluated in 108 patients with PSP (61 TT and 47 PD). Patients in both groups had comparable clinical characteristics. Drainage and hospitalisation duration were similar in TT and PD patients. There were no complications in either group. The immediate success rate was different: after prolonged drainage (>7 days), 10 out of 47 PD patients, but only 1 out of 61 TT patients required a TT as a second procedure. Total costs of hospitalisation including any treatment procedure were not significantly different between TT and PD patients. Pain, measured daily by visual analogue scales, was statistically higher during the first 3 days in TT patients but not in those patients receiving opiates. One month after leaving hospital, there was no significant difference in residual pain or full working ability: 20 out of 58 (34%) versus 10 out of 47 (21%) and 36 out of 61 (59%) versus 26 out of 39 (67%) in TT versus PD groups, respectively. After 5 yrs of follow-up, there had been only three out of 59 (5%) recurrences of pneumothorax after TT, but 16 out of 47 (34%) after conservative treatment by PD. Cost calculation favoured TT pleurodesis especially with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anaesthesia is superior to conservative treatment by chest tube drainage in cases of primary spontaneous pneumothorax that fail simple aspiration, provided there is efficient control of pain by opioids.

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.

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.

Does negative expiratory pressure influence performances of spirometry in older patients?

The aim of this study is to assess the influence of the negative expiratory pressure (NEP) technique on the performance of maximal expiratory manoeuvre in elderly patients. Firstly, the authors studied how NEP (at 5 and 10 cmH2O, NEP5 and NEP10) influences forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 60 young healthy volunteers, in order to assess the fluctuations of the method. In the second part of the study, 65 successive elderly inpatients (>70 yrs old) were examined. In this group, 15 elderly patients were unable to perform the manoeuvre, 27 had a normal function, 14 had a lung function with obstructive pattern and nine with restrictive pattern. In young subjects, FVC during NEP5 and NEP10 compared to baseline values was 101+/-5%, and 103+/-5%, respectively, and FEV1 was 100+/-4% and 101+/-5%, respectively. In elderly patients with normal function, FVC during NEP5 and NEP10 compared to baseline values was 99+/-14% and 109+/-23%, respectively, and FEV1 was 97+/-9% and 104+/-13%, respectively. There were no relevant effects of the NEP application on FVC or FEV1 values in elderly patients with an obstructive or restrictive pattern. In elderly patients, the use of the negative expiratory pressure technique during maximal expiratory manoeuvres provides little complementary information compared to a classical manoeuvre. The negative expiratory pressure technique did not modify the initial diagnosis when compared with the classical manoeuvre.

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.

Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation.

The aim of the present study was to compare the evolution of pulmonary haemodynamics and of arterial blood gases in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate hypoxaemia, with or without sleep-related oxygen desaturation. COPD patients with daytime arterial oxygen partial pressure in the range 56-69 mmHg were included prospectively. Sleep-related oxygen desaturation was defined as spending > or = 30% of the nocturnal recording time with arterial oxygen saturation <90%. From the 64 patients included, 35 were desaturators (group 1) and 29 were nondesaturators (group 2). At baseline (t0), patients with sleep-related desaturation had a significantly higher daytime (mean +/- SD) arterial carbon dioxide partial pressure (Pa,CO2) (44.9 +/- 4.9 mmHg versus 41.0 +/- 4.1 mmHg, p=0.001) whereas mean pulmonary artery pressure (mPAP) was similar in the two groups. After 2 yrs (t2) of follow-up, 22 desaturators and 14 nondesaturators could be re-evaluated, including pulmonary haemodynamic measurements. None of the nondesaturator patients became desaturators at t2. The difference between the two groups in terms of daytime Pa,CO2 was still present at t2. The mean changes in mPAP from t0 to t2 were similar between the two groups, as were the rates of death or requirement for long-term oxygen therapy (American Thoracic Society criteria) during follow-up of up to 6 yrs. The presence of sleep-related oxygen desaturation is not a transitional state before the worsening of daytime arterial blood gases, but is a characteristic of some chronic obstructive pulmonary disease patients who have a higher daytime arterial carbon dioxide partial pressure. Such isolated nocturnal hypoxaemia or sleep-related worsening of moderate daytime hypoxaemia does not appear to favour the development of pulmonary hypertension, nor to lead to worsening of daytime blood gases.

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.

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.

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.

[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.

A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients.

The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.