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Biomedical subjects

M Estenne

Publications and source records attributed to M Estenne.

At least 19 recordsLinked to original sources

[Surgery for emphysema: recent advances].

INTRODUCTION: The treatment of chronic obstructive pulmonary disease has progressed considerably over the past 40 Years but, for most patients with advanced disease, medical management does not often produce more than limited benefits, particularly in terms of quality of life. STATE OF ART: Over the last decade the surgical treatment of emphysema, which was previously limited to bullectomy, has seen important developments: for carefully selected patients lung Volume reduction surgery and lung transplantation now offer the possibility of real symptomatic improvement and even prolonged survival. Thanks to the thousands of patients who have received these treatments our understanding of the pathophysiological mechanisms, surgical techniques, risks and benefits, medium and long-term results, and selection criteria has improved considerably. PERSPECTIVES AND CONCLUSIONS: This review summarises the most important aspects of these developments and discusses the role of Volume reduction and lung transplantation in the treatment of advanced emphysema.

Cost-Benefit Analysis↗

Preferential reduction of quadriceps over respiratory muscle strength and bulk after lung transplantation for cystic fibrosis.

BACKGROUND: In the absence of complications, recipients of lung transplants for cystic fibrosis have normal pulmonary function but the impact of the procedure on the strength and bulk of respiratory and limb muscles has not been studied. METHODS: Twelve stable patients who had undergone lung transplantation for cystic fibrosis 48 months earlier (range 8-95) and 12 normal subjects matched for age, height, and sex were studied. The following parameters were measured: standard lung function, peak oxygen uptake by cycle ergometry, diaphragm surface area by computed tomographic (CT) scanning, diaphragm and abdominal muscle thickness by ultrasonography, twitch transdiaphragmatic and gastric pressures, quadriceps isokinetic strength, and quadriceps cross section by CT scanning, and lean body mass. Diaphragm mass was computed from diaphragm surface area and thickness. RESULTS: Twitch transdiaphragmatic and gastric pressures, diaphragm mass, and abdominal muscle thickness were similar in the two groups but quadriceps strength and cross section were decreased by nearly 30% in the patients. Patients had preserved quadriceps strength per unit cross section but reduced quadriceps cross section per unit lean body mass. The cumulative dose of corticosteroids was an independent predictor of quadriceps atrophy. Peak oxygen uptake showed positive correlations with quadriceps strength and cross section in the two groups, but peak oxygen uptake per unit quadriceps strength or cross section was reduced in the patient group. CONCLUSIONS: The diaphragm and abdominal muscles have preserved strength and bulk in patients transplanted for cystic fibrosis but the quadriceps is weak due to muscle atrophy. This atrophy is caused in part by corticosteroid therapy and correlates with the reduction in exercise capacity.

Abdominal Muscles↗

Bayesian forecasting of oral cyclosporin pharmacokinetics in stable lung transplant recipients with and without cystic fibrosis.

The aims of the current study were (1) to study Neoral pharmacokinetics (PK) in stable lung recipients with or without cystic fibrosis (CF), (2) to compare Neoral PK between these two groups, and (3) to design Bayesian estimators for PK forecasting and dose adjustment in these patients using a limited number of blood samples. The individual PK of 19 adult lung transplant recipients, 9 subjects with CF and 10 subjects without CF, were retrospectively studied. Three profiles obtained within 5 days were available for each patient. A PK model combining a gamma distribution to describe the absorption profile and a two-compartment model were applied. Different exposure indices were estimated using nonlinear regression and Bayesian estimation. The PK model developed reliably described the individual PK of Neoral in lung transplant patients with and without CF, and the values of the first and second half-lives were different in these two populations (lambda(1) = 4.14 +/- 3.01 vs. 2.16 +/- 1.75 h(-1); P < 0.01; lambda(2) = 0.36 +/- 0.11 vs. 0.49 +/- 0.12 h(-1); P < 0.01), while the mean absorption time and standard deviation of absorption time tended to be less in patients with cystic fibrosis (P < 0.1). Also, the patients with CF required higher doses than those without CF to achieve similar drug exposure. Consequently, population modeling was performed in CF and non-CF patients separately. Bayesian estimation allowed accurate prediction of AUC(0-12), AUC(0-4), C(max), and T(max) using three blood samples collected at T0h, T1h, and T3h in both groups. This study demonstrated the applicability and good performance of the PK model previously developed for oral cyclosporin and of the MAP Bayesian estimation of cyclosporin systemic exposure in CF and non-CF patients. Moreover, it is the first to propose a monitoring tool specifically designed for cyclosporin monitoring in patients with CF.

Administration, Oral↗

Indications, patient selection and timing of referral for lung transplantation.

Lung transplantation (LTx) is now generally accepted as a useful modality of care for patients with severe life-threatening respiratory diseases that are refractory to other medical or surgical therapies. With the huge development of LTx over the last 15 yrs, the disparity between the number of potential recipients and the number of donor organs available has become a major constraint, with many patients dying on the waiting lists. Therefore, it is of primary importance to control and optimise the use of this limited organ resource by weighting the risks and benefits of transplantation in individual patients, and to identify those patients who have a better chance of having a favourable outcome with transplantation. This article discusses the selection process of potential candidates and the currently accepted absolute and relative contraindications, and proposes general and disease-specific recommendations for optimising the timing of referral. Early referral for consideration of lung transplantation is highly desirable as it enhances the patient's chance of surviving to transplant and allows the transplant team to actively manage identified comorbidities during the waiting period.

Contraindications↗

Post-transplant bronchiolitis obliterans.

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50-60% of patients who survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring after the third postoperative year. This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.

Animals↗

[The pneumology department].

The department of pneumology of the Erasme hospital exists since 25 years. The basic clinical activities include pulmonary function testing (7,500 patients per year), endoscopy, including interventional endoscopy (1,500 patients per year), thoracic oncology, allergology, rehabilitation and aid to smoking cessation. The following expertise fields have been largely developed: lung transplantation, treatment of cystic fibrosis in collaboration with the children's hospital Reine Fabiola, occupational.

Belgium↗

Involvement of peripheral airways during methacholine-induced bronchoconstriction after lung transplantation.

Previous studies have shown that the presence of nonspecific bronchial hyperreactivity (NSBHR) in transplanted subjects is associated with the development of bronchiolitis obliterans, which suggests that NSBHR in these subjects may involve the peripheral airways. We investigated this question by studying the effects of methacholine on the distribution of ventilation using single-breath washouts in 15 heart-lung transplant recipients; 17 nontransplanted subjects with NSBHR were studied for comparison. All subjects had normal baseline lung function, and seven transplanted subjects displayed NSBHR. Methacholine induced a similar decline in FEV1 and specific airway conductance in the two groups. In contrast, whereas methacholine produced similar increases in the slope of the alveolar plateau for SF6 (SSF6) and He (SHe) in the nontransplanted subjects, it always produced greater increases in SHe than SSF6 in the transplanted subjects. This suggests that in the latter, methacholine-induced bronchoconstriction made the distribution of ventilation more heterogeneous in peripheral airways. This involvement of small airways may help in understanding why assessing bronchial reactivity in transplanted subjects provides information on the presence of a pathologic process affecting the bronchioles, and hence on the risk of progression to bronchiolitis obliterans.

Adolescent↗

Bronchiolitis obliterans syndrome in heart-lung transplant recipients: diagnosis with expiratory CT.

PURPOSE: To determine the test performance and longitudinal evolution of air trapping for diagnosing bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Over 7 years, 111 combined inspiratory and expiratory computed tomographic examinations were performed in eight healthy control subjects and 38 heart-lung transplant recipients. Functional impairment was assessed with the BOS classification. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of air trapping to distinguish between patients with and those without BOS and to compute sensitivity and specificity for diagnosing BOS. RESULTS: The extent of air trapping increased with BOS severity (P =.001). A threshold of 32% of air trapping is optimal for distinguishing between patients with and those without BOS and provides a sensitivity of 83%, a specificity of 89%, and an accuracy of 88%. The prevalence of BOS and positive predictive value of air trapping increased with postoperative time, but the negative predictive value of air trapping remained high throughout the study. Patients without BOS who had air trapping exceeding 32% of the parenchyma were at significantly increased risk of developing BOS (P =.004). CONCLUSION: At the threshold of 32%, air trapping is sensitive, specific, and accurate for diagnosing BOS. Patients with air trapping below 32% are unlikely to have BOS. Air trapping exceeding 32% may be an early indicator of future BOS.

Adult↗

Effects of lung volume reduction surgery for emphysema on diaphragm dimensions and configuration.

Part of the functional benefit provided by lung volume reduction surgery (LVRS) may be related to improvement in respiratory muscle function resulting from changes in diaphragm dimension and configuration. To study these changes, we obtained 3D reconstructions of the muscle using spiral computed tomography in 11 patients with severe emphysema before and 3 mo after surgery, and in 11 normal subjects matched for sex, age, height, and weight. Bilateral LVRS was performed by thoracoscopy in eight patients and by sternotomy in three patients. Acquisitions were made in the supine posture at relaxed FRC, midinspiratory capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and a 30 +/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and of the zone of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%, respectively, but the surface area of the dome did not change. Compared with the values recorded in the normal subjects, postoperative values of A(di) and A(ap) at FRC were reduced by 11% (p < 0.05) and 24% (p < 0.005), respectively. The curvature of the dome increased at TLC in the left sagittal plane, but was otherwise unaffected by the procedure. We conclude that LVRS substantially increases A(di) and A(ap), but does not significantly improve diaphragm configuration at FRC.

Anthropometry↗

Impaired antigen-presenting cell function contributes to T-cell hyporesponsiveness in stable lung transplant recipients.

BACKGROUND: Peripheral blood mononuclear cells (PBMC) of stable renal or cardiac transplant recipients were previously shown to respond to allogeneic cells but not to soluble protein antigens. The aim of the present study was to assess the T-cell and antigen-presenting cell (APC) functions of stable lung transplant (LT) recipients. METHODS: We obtained PBMC from 38 stable LT recipients. PBMC from healthy volunteers served as controls. PBMC were stimulated with either anti-CD3 monoclonal antibody, allogeneic PBMC, or tetanus toxoid (TT). T-cell activation was assessed by determination of interleukin (IL)-2 levels in culture supernatants; in some experiments, interferon-y levels were also determined. Patients' APC function was tested in a mixed leukocyte reaction using patients' PBMC as stimulators. The expression of class II MHC, B7.2, and CD40 molecules on patients' APC was determined by flow cytometry, and their production of IL-10 and IL-12 at the basal state and upon CD40 ligation was also measured. RESULTS: Patients' T cells produced normal amounts of IL-2 in response to anti-CD3 monoclonal antibody and allogeneic PBMC. In contrast, the response of memory T cells to TT was severely blunted both in terms of IL-2 and interferon-y production. Patients' PBMC were poor stimulators in mixed leukocyte reaction, and class II MHC expression on patients' monocytes was significantly reduced. Patients' APC presented a modest but significant increase in basal IL-10 production and produced significantly less IL-12 upon CD40 ligation than control APC. CONCLUSIONS: T cells from stable LT recipients respond normally to stimuli that do not depend on autologous APC. The major impairment in the T-cell response to TT is caused by APC dysfunction, which involves decreased class II MHC expression and deficient IL-12 synthesis.

Antigen-Presenting Cells↗

Effect of preoperative hyperinflation on static lung volumes after lung transplantation.

It is still not known whether persistent increases in functional residual capacity (FRC) and residual volume (RV) after lung transplantation are due to preexisting hyperinflation. Therefore, the aim of this study was to determine the effects of chronic lung hyperinflation on static lung volumes after heart/lung (HLT) and bilateral lung transplantation (BLT). Static lung volumes were measured in 33 patients before and at 6 month intervals for up to 3 yrs after HLT (n=25) or BLT (n=8). The preoperative diagnosis was cystic fibrosis in 25 patients and other chronic hyperinflated lung diseases in eight patients. After surgery, total lung capacity returned to predicted normal values but FRC and RV remained greater than expected for either the recipient or the donor. At 1 yr after surgery, mean+/-SD FRC and RV were 130+/-18% and 151+/-34% of the predicted values for the recipient (p<0.001), and these figures did not change significantly over time. Similar abnormalities were found in patients with and without cystic fibrosis. After transplantation for lung diseases producing chronic hyperinflation, there is a persistent increase in functional residual capacity and residual volume. This alteration is present in patients operated on for diseases developed in both childhood and adulthood and is not recovered over time. It may be due to irreversible changes in the structure of the ribcage.

Adult↗

Obliterative bronchiolitis after lung transplantation.

Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by obliterative bronchiolitis (OB). Thought to be a manifestation of chronic allograft rejection, OB affects up to 65% of patients at 5 years after surgery and produces a relentless airflow obstruction. Early and late acute rejection are the primary risk factors for OB, but cytomegalovirus infection and airway ischemia may also play a role. In most patients, OB responds poorly to augmented immunosuppression and eventually leads to infectious complications and terminal respiratory failure. Because early diagnosis is associated with better prognosis, every effort should be made to detect OB in a preclinical stage. This may be best achieved by combining several techniques, such as surveillance transbronchial biopsy and bronchoalveolar lavage, measurements of ventilation distribution and exhaled nitric oxide, and expiratory computed tomography.

Anti-Inflammatory Agents↗

Abdominal muscle strength in patients with tetraplegia.

The abdominal muscles are completely paralyzed after traumatic transection of the cervical cord. To assess the residual pressure-generating capacity of these muscles, we first measured the changes in gastric pressure (DeltaPga) during paired bilateral stimulation of the lower thoracic nerve roots in eight chronic patients with C5-C7 tetraplegia and eight matched unaffected subjects in the seated posture. Stimulations were applied with a 90-mm circular magnetic coil positioned at the level of T10 and connected to a Magstim 250 stimulator. During relaxation at FRC, DeltaPga during maximal stimulation averaged (mean +/- SE) 76.0 +/- 11.7 cm H(2)O in the control subjects, whereas in the patients it was only 29.9 +/- 3.7 cm H(2)O (p = 0.002). Stimulations were next applied during the course of a forced expiration. All patients consistently demonstrated an abrupt increase in esophageal pressure (22.7 +/- 4.5 cm H(2)O), and six of them also showed an increase in expiratory flow. The cumulative thickness of the four abdominal muscles, as measured with an ultrasound probe, was 34% smaller in the patients than in the control subjects and correlated positively with maximal DeltaPga. We conclude that in patients with tetraplegia, muscle atrophy causes a marked reduction in abdominal muscle strength. However, magnetic stimulation of the abdominal muscles elicits increases in intrathoracic pressure that are greater than those required to initiate dynamic airway compression; it might, therefore, improve the clearing of airway secretions.

Abdominal Muscles↗

Detection of obliterative bronchiolitis after lung transplantation by indexes of ventilation distribution.

Obliterative bronchiolitis (OB) is the first cause of death of long-term survivors of lung transplantation. The diagnosis is based on pathology and/or on an irreversible decrease in forced expiratory volume in 1 s (FEV(1)) below 80% of the best postoperative value. We tested whether indexes of ventilation distribution may provide evidence of OB before conventional pulmonary function tests (PFTs). Fifty-seven patients with heart-lung (n = 47) or double-lung (n = 10) transplantation were monitored with conventional PFTs and measurements of the slope of the alveolar plateau for He (S(He)), SF(6) (S(SF6)), and N(2) (S(N2)) obtained during single-breath washouts. The date at which a functional variable showed an irreversible change outside the 97.5% confidence interval was compared with the date at which a greater than 20% fall in FEV(1) was observed. A total of 1,929 tests (median, 30 tests per patient) were performed during the 1,215 d (range, 164-2,829 d) of follow-up. Eighteen patients showed an irreversible and greater than 20% fall in FEV(1) during the course of the study. This alteration was preceded by a rise in S(He) in 17 patients and by a rise in S(N2) in 16 patients, which indicated a more heterogeneous ventilation. The median time interval between the change in S(He) and S(N2) and the 20% decrease in FEV(1) was 356 and 168 d, respectively, with seven patients showing an interval of 18 mo or more. Conventional PFTs, including midexpiratory flow rates, deteriorated after indexes of ventilation distribution. Thirty-nine patients did not show any significant and irreversible alteration in conventional PFTs over the study period; only seven of these patients developed significant alterations in ventilation distribution. We conclude that measurements of ventilation distribution detect posttransplant OB much earlier than conventional PFTs.

Adult↗