Marc Estenne

INTERNATIONAL GUIDELINES FOR THE SELECTION OF LUNG TRANSPLANT CANDIDATES

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A review of lung transplant donor acceptability criteria

Abstract (A consensus report from The Pulmonary Council of the International Society for Heart and Lung Transplantation)

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS. A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations. The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of post-transplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS. The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention. Diagnosis of BOS requires careful exclusion of other complications that can cause delayed lung allograft dysfunction http://ow.ly/AZmbr

Mechanism of relief of dyspnea after thoracocentesis in patients with large pleural effusions

In an attempt to understand the mechanism underlying the relief of dyspnea that follows thoracocentesis in patients with large pleural effusions, we measured respiratory mechanics in nine patients before and two hours after removal of 600 to 2,750 ml (mean = 1,818 ml) of pleural fluid. Thoracocentesis resulted in only small changes in pulmonary mechanics: Mean vital capacity and functional residual capacity increased by 300 and 460 ml, respectively, lung recoil pressure slightly decreased, and mean static expiratory compliance increased by 0.021 liter/cm H2O. These changes were inconsistent and could not explain the immediate and remarkable relief of dyspnea noted by the patients. By contrast, thoracocentesis invariably resulted in a shift of the minimal (inspiratory) pleural pressure-volume curve so that the pressures generated by the inspiratory muscles were markedly more negative at any comparable lung volume. This shift was entirely due to the decrease in thoracic cage volume. We suggest that the relief of dyspnea following thoracocentesis results primarily from reduction in size of the thoracic cage, which allows the inspiratory muscles to operate on a more advantageous portion of their length-tension curve.

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.

Mechanism of Active Expiration in Tetraplegic Subjects

Traumatic tetraplegia produces paralysis of all the well-recognized muscles of expiration. Yet, tetraplegic subjects usually have a small expiratory reserve volume on spirographic examination. To understand the mechanism that enables these patients to empty their lungs actively, we studied the pattern of chest-wall motion during voluntary expiration. We found negligible changes in abdominal dimension, but all subjects had a marked and reproducible decrease in the dimension of the upper rib cage. Electrical measurements established that the subjects had active use of the clavicular portion of the pectoralis major, and changing the orientation of these muscle fibers by maintaining the shoulders in abduction reduced their expiratory reserve volume by about 60 percent (P less than 0.001). We therefore conclude that the clavicular portion of the pectoralis major plays a crucial part in the mechanism of active expiration in tetraplegic subjects. Training of this muscle bundle could, by increasing its strength and endurance, improve the effectiveness of coughing in such subjects and perhaps diminish the prevalence of bronchopulmonary infections.

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 patients chance of surviving to transplant and allows the transplant team to actively manage identified comorbidities during the waiting period.

Cough in tetraplegic subjects: an active process.

STUDY OBJECTIVE To determine the role of the clavicular portion of the pectoralis major during cough in tetraplegic subjects. PATIENTS Eight patients with longstanding traumatic transection of the lower cervical cord. METHODS The electromyographic activity of the pectoralis major and abdominal external oblique muscles and the changes in the anteroposterior diameter of the lower rib cage, the upper rib cage, and the abdomen were measured during voluntary coughing efforts in the seated posture. RESULTS When coughing, all subjects showed a large amount of electrical activity in the pectoralis major with no activity in the external oblique. Simultaneously, they had a clear-cut decrease in the anteroposterior diameter of the upper rib cage together with an increase in the anteroposterior diameter of the abdomen. In five subjects, the anteroposterior diameter of the lower rib cage also showed an initial increase. These changes were seen when cough was initiated at functional residual capacity or at a higher lung volume; they were also seen during a fit of coughing. CONCLUSIONS In tetraplegic subjects the clavicular portion of the pectoralis major plays a major role during coughing. Its contraction causes a reduction in the size of the upper part of the rib cage and a rise in intrathoracic pressure; this pressure rise results secondarily in an outward (paradoxical) motion of the abdomen and the lower rib cage. Cough in tetraplegic subjects is thus an active, rather than a passive, process, and its effectiveness might be improved by a combination of specific muscle training and abdominal binding.

Limitations of measurement of transdiaphragmatic pressure in detecting diaphragmatic weakness.

Intrathoracic (oesophageal), intra-abdominal (gastric), and transdiaphragmatic (Pdi) pressures were studied in 20 untrained, healthy subjects during a full inspiration and repeated maximal static inspiratory efforts. The pattern of pressure generation during these two types of respiratory manoeuvre was highly reproducible in each subject. By contrast, it varied over a wide range among individuals. In particular a substantial number of subjects naturally had a strong recruitment of their intercostal and accessory muscles and thus, low Pdi values, during both slowly performed and forceful inspiratory manoeuvres. These observations make it clear that Pdi values, as usually obtained, are commonly open to misinterpretation. For this approach to ensure a reliable assessment of diaphragmatic function and detect diaphragm weakness adequately, it appears essential either to monitor the abdominothoracic configuration or to standardise the pattern of respiratory muscle contraction.

Human herpesvirus-6 infection after lung and heart-lung transplantation: A prospective longitudinal study

Background. Although human herpesvirus (HHV)-6 is now recognized as a frequent pathogen after transplantation, the real impact of this infection in patients undergoing transplantation remains unclear. Methods. During 27 months, 30 consecutive heart–lung- and lung-transplant recipients were included on the day of transplantation and prospectively followed during 100 days for HHV-6 infection. Results. HHV-6 infection occurred in 20 (66%) patients after a median delay of 18 days after transplantation. The virus was detected by polymerase chain reaction or culture, or both, in 15.7 % of blood specimens, in 14.5% of bronchoalveolar lavage fluids, and in many organs at postmortem examination; it was found by culture in eight patients. No clinical manifestations could clearly be associated with HHV-6 alone. However, patients with HHV-6 infection had a higher mortality rate than patients without HHV-6 infection (7 of 20 vs. 0 of 10; P =0.04), and all the deceased patients died during periods of HHV-6 infection. We did not observe higher incidence of infectious or graft-rejection episodes in HHV–6-positive patients. However, eight of nine viral or fungal infections occurred during HHV-6 infection and three were directly responsible for death. Conclusion. Although frequently detected after transplantation, HHV-6 was not associated with any specific clinical manifestation. The higher mortality rate observed in patients with HHV-6 infection was not related to a higher incidence of bacterial infections or graft rejection but might be associated with more viral and fungal infections.