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Seminars in Respiratory and Critical Care Medicine

Rupal J Shah, Joshua M Diamond
Primary graft dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung allograft dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics...
April 2018: Seminars in Respiratory and Critical Care Medicine
Nicholas A Kolaitis, Jonathan P Singer
Lung transplantation (LT) has the potential to extend survival and improve quality of life (QOL) for patients suffering from end-stage lung disease. This review describes the many ways in which success can be defined in LT. It evaluates the improvements in survival outcomes after LT over time, and describes ways to measure the success of LT other than survival after transplantation. It also addresses the importance of patient-centered outcomes and how improvements in health-related quality of life (HRQL) are pivotal to defining success within LT...
April 2018: Seminars in Respiratory and Critical Care Medicine
Nina M Clark, S Samuel Weigt, Michael C Fishbein, Bernard Kubak, John A Belperio, Joseph P Lynch
Lung transplantation is an increasingly utilized modality for treating advanced lung disease. However, lung transplant recipients (LTRs) experience high rates of infection-related mortality and, compared with other solid organ transplant recipients, are at increased risk of infectious complications given the intensity of immunosuppression employed, the presence of airway abnormalities after surgery and exposure of the allograft to the environment. Fungal infections, particularly mold infections, are problematic after transplantation as they are often associated with limited treatment options and poor outcomes...
April 2018: Seminars in Respiratory and Critical Care Medicine
Mark Benzimra
The performance of bronchoscopy with bronchoalveolar lavage and transbronchial biopsy is an essential tool and skill required by any clinician caring for patients postlung transplantation. Making a confident diagnosis is crucial in initiating different treatment strategies which may be in turn hazardous to the patient in light of an inaccurate diagnosis. Having more information available for evaluation optimizes the chances of tailoring appropriate therapeutic options in this complex patient population. Performing a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy indeed provides a wealth of information via microbiological, cytological, and histological samples that assist us to differentiate infection from rejection, or to confirm the presence of both...
April 2018: Seminars in Respiratory and Critical Care Medicine
Jens Gottlieb
The incidence of community-acquired respiratory viruses (CARVs) is ∼15 cases per 100 patient-years after lung transplantation (LTx). Paramyxoviruses account for almost 50% of the cases of CARV infection in LTx. Most patients will be symptomatic with a mean decline of 15 to 20% in forced expiratory volume in 1 second. The attributable death rate is low in recent years 15 to 25% CARV infected LTx patients will develop chronic lung allograft dysfunction within a year after CARV infection. This risk seems to be increased in comparison to the noninfected LTx recipient...
April 2018: Seminars in Respiratory and Critical Care Medicine
Alicia B Mitchell, Allan R Glanville
Once considered a sterile site below the larynx, the tracheobronchial tree and parenchyma of the lungs are now known to harbor a rich diversity of microbial species including bacteria, viruses, fungi, and archaea. Many of these organisms, particularly the viruses which comprise the human respiratory virome, have not been identified, so their true role is unknown. It seems logical to conclude that a "healthy" respiratory microbiome exists which may be modified in disease states and perhaps by therapies such as antibiotics, antifungals, and antiviral treatments...
April 2018: Seminars in Respiratory and Critical Care Medicine
Angela Koutsokera, Liran Levy, Prodipto Pal, Ani Orchanian-Cheff, Tereza Martinu
Despite significant progress in the field of transplant immunology, acute cellular rejection (ACR) remains a very frequent complication after lung transplantation (LTx), with almost 30% of LTx recipients experiencing at least one episode of treated ACR during the first year of follow-up. Most episodes respond to the first-line immunosuppressive treatment and are rarely a direct cause of death. However, the association of ACR with later adverse outcomes, such as chronic lung allograft dysfunction, bronchial stricture, and infectious complications associated with the intensification of immunosuppression, negatively impacts long-term survival...
April 2018: Seminars in Respiratory and Critical Care Medicine
Ramsey R Hachem
Outcomes after lung transplantation remain disappointing because there is a high incidence of chronic lung allograft dysfunction (CLAD), which typically follows a progressive clinical course and often results in allograft failure and death. Chronic rejection is considered the predominant cause of CLAD. Thus, optimal immunosuppression has been viewed as having the potential to prevent CLAD and improve survival after lung transplantation. Numerous clinical trials have been conducted investigating the efficacy and safety of various immunosuppressive agents...
April 2018: Seminars in Respiratory and Critical Care Medicine
Ariss DerHovanessian, W Dean Wallace, Joseph P Lynch, John A Belperio, S Sam Weigt
Lung transplantation has become an established therapeutic option for a variety of end-stage lung diseases. Technical advances in graft procurement, implantation, perioperative care, immunosuppression, and posttransplant medical management have led to significant improvements in 1-year survival, but outcomes after the first year have improved minimally over the last two decades. The main limitation to better long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care...
April 2018: Seminars in Respiratory and Critical Care Medicine
Gregory I Snell, Bronwyn J Levvey, Kovi Levin, Miranda Paraskeva, Glen Westall
Lung transplantation (LTx) has traditionally been limited by a lack of suitable donor lungs. With the recognition that lungs are more robust than initially thought, the size of the donor pool of available lungs has increased dramatically in the past decade. Donation after brain death (DBD) and donation after circulatory death (DCD) lungs, both ideal and extended are now routinely utilized. DBD lungs can be damaged. There are important differences in the public's understanding, legal and consent processes, intensive care unit strategies, lung pathophysiology, logistics, and potential-to-actual donor conversion rates between DBD and DCD...
April 2018: Seminars in Respiratory and Critical Care Medicine
Thomas M Egan
As lung transplantation became established therapy for end-stage lung disease, there were not nearly enough suitable lungs from brain-dead organ donors to meet the need, leading to a focus on how lungs are allocated for transplant. Originally lungs were allocated by the United Network for Organ Sharing (UNOS) like hearts-by waiting time, first to listed recipients in the organ procurement organization of the donor, then to potential recipients in concentric 500 nautical mile circles. This resulted in long waiting times and increasing waitlist deaths...
April 2018: Seminars in Respiratory and Critical Care Medicine
Jonathan B Orens, Christian A Merlo
Lung transplantation is a widely accepted treatment to manage the advanced stages of many lung diseases that have failed to respond to all other therapeutic interventions. There have been ever-expanding indications for lung transplantation as a treatment for lung disease. The International Society for Heart and Lung Transplantation (ISHLT) updated guidelines for candidate selection in 2014. This document was published to serve as a guide in selecting appropriate candidates for lung transplantation. Ideal candidates for lung transplantation are those with near-end stage disease, limited life expectancy due to their lung disease, and who experience significant loss in quality of life...
April 2018: Seminars in Respiratory and Critical Care Medicine
John A Belperio, Allan R Glanville
No abstract text is available yet for this article.
April 2018: Seminars in Respiratory and Critical Care Medicine
Ravi K Viswanathan, William W Busse
Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease...
February 2018: Seminars in Respiratory and Critical Care Medicine
Kian Fan Chung
Severe therapy-resistant asthma has been defined as "asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy". Patients who usually present with 'difficult-to-treat asthma' should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant...
February 2018: Seminars in Respiratory and Critical Care Medicine
Helen K Reddel
Asthma management is in an intriguing phase, with acceptance of asthma as a heterogeneous condition with different phenotypes and underlying mechanisms and the potential for personalized asthma care, in parallel with increasing evidence about the population-level impact of basic strategies to increase access to medicines and improve inhaler technique and adherence. These changes have been facilitated by a more comprehensive view of evidence, including both randomized controlled trials with high internal validity and pragmatic and observational studies with high generalizability to patients in clinical practice...
February 2018: Seminars in Respiratory and Critical Care Medicine
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
Hui Fang Lim, Parameswaran Nair
Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E...
February 2018: Seminars in Respiratory and Critical Care Medicine
Peter A B Wark, James Michael Ramsahai, Prabuddha Pathinayake, Bilal Malik, Nathan W Bartlett
Asthma remains the most prevalent chronic respiratory disorder, affecting people of all ages. The relationship between respiratory virus infection and asthma has long been recognized, though remains incompletely understood. In this article, we will address key issues around this relationship. These will include the crucial role virus infection plays in early life, as a potential risk factor for the development of asthma and lung disease. We will assess the impact that virus infection has on those with established asthma as a trigger for acute disease and how this may influence asthma throughout life...
February 2018: Seminars in Respiratory and Critical Care Medicine
William C Anderson, Stanley J Szefler
Strategies to control the risk domain of NHLBI EPR-3 (National Heart, Lung, and Blood Institute Expert Panel Report-3) asthma guidelines, which includes exacerbations requiring systemic corticosteroids, reduction in lung growth, and progressive loss of lung function, and treatment-related adverse effects, are evolving in children and adolescents. Increasing evidence demonstrates that children and adolescents with asthma are at risk of a reduction in lung growth, leading to lower lung function and potentially chronic obstructive pulmonary disease as adults...
February 2018: Seminars in Respiratory and Critical Care Medicine
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