Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2013
ReviewBronchiolitis obliterans syndrome: the Achilles' heel of lung transplantation.
Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft dysfunction (CLAD), most commonly manifest as bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. ⋯ There are few controlled studies assessing treatment efficacy, but only a minority of patients respond to current treatment modalities. Ultimately, preventive strategies may prove more effective at prolonging survival after lung transplantation, but their remains considerable debate and little data regarding the best strategies to prevent BOS. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome.
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Semin Respir Crit Care Med · Jun 2013
ReviewNeutrophilic reversible allograft dysfunction (NRAD) and restrictive allograft syndrome (RAS).
Lung transplantation is currently considered as an ultimate live-saving treatment for selected patients suffering from end-stage pulmonary disease. Long-term survival, however, is hampered by chronic rejection, or chronic lung allograft dysfunction (CLAD). Recently, various phenotypes within CLAD have been identified, challenging the established clinical definition of bronchiolitis obliterans syndrome (BOS). ⋯ This phenotype is called restrictive allograft syndrome (RAS), and patients with RAS have a much worse prognosis after diagnosis. This review further discusses both of these CLAD phenotypes that do not fit the classical definition of BOS. Potential pathophysiological mechanisms, etiology, diagnosis, prognosis, and treatments are discussed.
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Semin Respir Crit Care Med · Jun 2013
ReviewLung transplantation for cystic fibrosis and bronchiectasis.
Lung transplantation has become an excellent treatment option for patients with cystic fibrosis (CF) and bronchiectasis with very advanced lung disease. Despite the challenges that the CF patients present, survival is more favorable than that seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although those CF and bronchiectasis patients with severe respiratory disease are often infected with organisms that display in vitro resistance to the commonly used antibiotics, they usually have successful outcomes with transplantation, which are reported to be the same as in those patients with less resistant bacteria. ⋯ Efforts to increase the donor pool, such as low tidal volume ventilation, are effective in allowing a greater percentage of offered organs to be accepted. Perhaps the most encouraging development, however, is that of ex vivo lung perfusion. This permits not only the ability to measure the function of the lungs, something of great value for lungs from donors with circulatory death (donation after cardiac death), but also the potential to introduce lung repair and convert a nonusable lung to one that can be safely used for transplantation.
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Primary graft dysfunction (PGD) is a syndrome encompassing a spectrum of mild to severe lung injury that occurs within the first 72 hours after lung transplantation. PGD is characterized by pulmonary edema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. In recent years, new knowledge has been generated on risks and mechanisms of PGD. ⋯ Improved methods of reducing PGD risk and efforts to safely expand the pool are being developed. Ex vivo lung perfusion is a strategy that may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review details recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers, and state-of-the-art technical developments affecting PGD.
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Semin Respir Crit Care Med · Jun 2013
ReviewThe role of surveillance bronchoscopy post-lung transplantation.
Surveillance bronchoscopies with transbronchial lung biopsies (TBBx) are often performed post-lung transplantation, but the clinical value and impact on outcomes remain controversial. Given the cost and risks associated with TBBx, some centers only perform bronchoscopy for specific clinical indications or events. Although the presence of specific histological features (especially acute cellular rejection or lymphocytic bronchiolitis) have been associated with higher risk of chronic lung allograft rejection, the routine use of mandated TBBx has not been shown to alter clinical outcomes. ⋯ Further, there are limited published data regarding the value of performing follow-up TBBx to ensure resolution of prior rejection events. On the other hand, putative benefits of TBBx include the ability to fine tune immune suppression and detect infection and large airway stenoses that may require more aggressive measures to minimize development of strictures and thereby prevent downstream post obstructive bronchiectasis. This review discusses the technique of TBBx, histological criteria for allograft rejection (acute and chronic), complications associated with TBBx (particularly pneumothoraces, hypoxemia, and bleeding), and putative benefits associated with mandated surveillance TBBx in this complex patient population.