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Lung transplantation for interstitial lung disease
Siddhartha G. Kapnadak, Ganesh Raghu
doi : 10.1183/16000617.0017-2021
European Respiratory Review 30 (161) 210017
Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.
A scoping review of palliative care outcome measures in interstitial lung disease
Rebecca A. Gersten, Amanda C. Moale, Bhavna Seth, Judith B. Vick, Hannah Brown, Michelle N. Eakin, Stephen C. Mathai, Sonye K. Danoff
doi : 10.1183/16000617.0080-2021
European Respiratory Review 30 (161) 210080
Interstitial lung disease (ILD) confers a high mortality and symptom burden, substantially impacting quality of life. Studies evaluating palliative care in ILD are rapidly expanding. Uniform outcome measures are crucial to assessing the impact of palliative care in ILD. This scoping review evaluates existing outcome measures in general health-related quality of life (HRQoL), physical health, mental health, social health and advance care planning (ACP) domains in patients with ILD. Articles in English with quantitative assessment of at least one measure of general HRQoL, physical health, mental health, social health or ACP in patients with ILD were included. Searches across three databases yielded 3488 non-duplicate articles. 23 met eligibility criteria and included three randomised controlled trials (RCTs) or secondary analysis of an RCT (13%), three cross-sectional studies or secondary analysis of cross-sectional study (13%), one prospective study (4%) and 16 retrospective studies (70%). Among eligible articles, 25 distinct instruments were identified. Six studies assessed general HRQoL (26%), 16 assessed physical health (70%), 11 assessed mental health (48%), six assessed social health (26%) and 16 assessed ACP (70%). The ability to compare results across studies remains challenging given the heterogeneity in outcome measures. Future work is needed to develop core palliative care outcome measures in ILD.
Human pluripotent stem cells for the modelling and treatment of respiratory diseases
Pien A. Goldsteen, Christina Yoseif, Amalia M. Dolga, Reinoud Gosens
doi : 10.1183/16000617.0042-2021
European Respiratory Review 30 (161) 210042
Respiratory diseases are among the leading causes of morbidity and mortality worldwide, representing a major unmet medical need. New chemical entities rarely make it into the clinic to treat respiratory diseases, which is partially due to a lack of adequate predictive disease models and the limited availability of human lung tissues to model respiratory disease. Human pluripotent stem cells (hPSCs) may help fill this gap by serving as a scalable human in vitro model. In addition, human in vitro models of rare genetic mutations can be generated using hPSCs. hPSC-derived epithelial cells and organoids have already shown great potential for the understanding of disease mechanisms, for finding new potential targets by using high-throughput screening platforms, and for personalised treatments. These potentials can also be applied to other hPSC-derived lung cell types in the future. In this review, we will discuss how hPSCs have brought, and may continue to bring, major changes to the field of respiratory diseases by understanding the molecular mechanisms of the pathology and by finding efficient therapeutics.
Airway granulation response to lung-implantable medical devices: a concise overview
Sharyn A. Roodenburg, Simon D. Pouwels, Dirk-Jan Slebos
doi : 10.1183/16000617.0066-2021
European Respiratory Review 30 (161) 210066
Increasing numbers of endoscopically implantable devices are implanted in the airways, such as airway stents, one-way valves and coils, to treat both malignant and benign diseases. They significantly improve patient outcomes, but their long-term effectiveness and sustainability is hampered by the reaction of the formation of granulation tissue. Factors including procedural-related tissue injury; micro-organism presence; device-related factors, such as the material, design and sizing in relation to the airway; and patient-related factors, including genetic susceptibility, comorbidities and medication use, might all effect the severity of the tissue response and the subsequent degree of granulation tissue formation. However, research into the underlying mechanism and risk factors is scarce and therefore our knowledge is limited. Joint efforts from the scientific community, both pre-clinical and clinical, are needed to gain a deeper understanding and eventually improve the long-term treatment effectiveness of lung-implantable devices.
Liposomal drug delivery to manage nontuberculous mycobacterial pulmonary disease and other chronic lung infections
James D. Chalmers, Jakko van Ingen, Roald van der Laan, Jean-Louis Herrmann
doi : 10.1183/16000617.0010-2021
European Respiratory Review 30 (161) 210010
Nontuberculous mycobacterial (NTM) pulmonary disease is a chronic respiratory infection associated with declining lung function, radiological deterioration and significantly increased morbidity and mortality. Patients often have underlying lung conditions, particularly bronchiectasis and COPD. NTM pulmonary disease is difficult to treat because mycobacteria can evade host defences and antimicrobial therapy through extracellular persistence in biofilms and sequestration into macrophages. Management of NTM pulmonary disease remains challenging and outcomes are often poor, partly due to limited penetration of antibiotics into intracellular spaces and biofilms. Efficient drug delivery to the site of infection is therefore a key objective of treatment, but there is high variability in lung penetration by antibiotics. Inhalation is the most direct route of delivery and has demonstrated increased efficacy of antibiotics like amikacin compared with systemic administration. Liposomes are small, artificial, enclosed spherical vesicles, in which drug molecules can be encapsulated to provide controlled release, with potentially improved pharmacokinetics and reduced toxicity. They are especially useful for drugs where penetration of cell membranes is essential. Inhaled delivery of liposomal drug solutions can therefore facilitate direct access to macrophages in the lung where the infecting NTM may reside. A range of liposomal drugs are currently being evaluated in respiratory diseases.
Measuring pulmonary function in COPD using quantitative chest computed tomography analysis
Jens T. Bakker, Karin Klooster, Rozemarijn Vliegenthart, Dirk-Jan Slebos
doi : 10.1183/16000617.0031-2021
European Respiratory Review 30 (161) 210031
COPD is diagnosed and evaluated by pulmonary function testing (PFT). Chest computed tomography (CT) primarily serves a descriptive role for diagnosis and severity evaluation. CT densitometry-based emphysema quantification and lobar fissure integrity assessment are most commonly used, mainly for lung volume reduction purposes and scientific efforts.
Management of asthma exacerbations in the paediatric population: a systematic review
Sara Manti, Amelia Licari, Salvatore Leonardi, Gian Luigi Marseglia
doi : 10.1183/16000617.0367-2020
European Respiratory Review 30 (161) 200367
Background Asthma exacerbations in children is one of the most common medical conditions requiring urgent visits to primary healthcare providers or emergency departments, and even hospitalisations. Currently, there is significant variation in the management of asthma exacerbations expressed in guideline recommendations versus clinical practice. This disconnect affects diagnostic and treatment decisions for the clinician and patient.
Recent developments in the treatment of small cell lung cancer
Birgitta I. Hiddinga, Jo Raskin, Annelies Janssens, Patrick Pauwels, Jan P. Van Meerbeeck
doi : 10.1183/16000617.0079-2021
European Respiratory Review 30 (161) 210079
Small cell lung cancer (SCLC) comprises about 15% of all lung cancers. It is an aggressive disease, with early metastasis and a poor prognosis. Until recently, SCLC treatment remained relatively unchanged, with chemotherapy remaining the cornerstone of treatment. In this overview we will highlight the recent advances in the field of staging, surgery, radiotherapy and systemic treatment. Nevertheless, the prognosis remains dismal and there is a pressing need for new treatment options. We describe the progress that has been made in systemic treatment by repurposing existing drugs and the addition of targeted treatment. In recent years, immunotherapy entered the clinic with high expectations of its role in the treatment of SCLC. Unravelling of the genomic sequence revealed new possible targets that may act as biomarkers in future treatment of patients with SCLC. Hopefully, in the near future, we will be able to identify patients who may benefit from targeted therapy or immunotherapy to improve prognoses.
Cough symptom severity in patients with refractory or unexplained chronic cough: a systematic survey and conceptual framework
Elena Kum, Gordon H. Guyatt, Tahira Devji, Yuting Wang, Layla Bakaa, Lucy Lan, Eva Liu, Alexander Mastrolonardo, Rachel Couban, Paul M. O'Byrne, Imran Satia
doi : 10.1183/16000617.0104-2021
European Respiratory Review 30 (161) 210104
Background Cough severity represents an important subjective endpoint in assessing the effectiveness of therapies for patients with chronic cough. Although cough-specific quality of life questionnaires exist, a widely available cough severity instrument with established measurement properties remains unavailable.Aims To identify and summarise the results of studies reporting on the experience of patients with chronic cough and, in the process, develop a conceptual framework to inform development of a patient-reported outcome measurement (PROM) addressing cough severity.
Update on recent key publications in lung oncology: picking up speed
Achim Rittmeyer, Annett Schiwitza, Lejla Sahovic, Bastian Eul, Stefan Andreas
doi : 10.1183/16000617.0300-2020
European Respiratory Review 30 (161) 200300
Introduction As incidence rates for lung cancer are still very high and lung cancer remains the most deadly cancer since the turn of the millennium, efforts have been made to find new approaches in cancer research. This systematic review highlights how therapeutic options were extended and how the development of new drugs has picked up speed during the last 20?years.
Update on molecular pathology and role of liquid biopsy in nonsmall cell lung cancer
Pamela Abdayem, David Planchard
doi : 10.1183/16000617.0294-2020
European Respiratory Review 30 (161) 200294
Personalised medicine, an essential component of modern thoracic oncology, has been evolving continuously ever since the discovery of the epidermal growth factor receptor and its tyrosine kinase inhibitors. Today, screening for driver alterations in patients with advanced lung adenocarcinoma as well as those with squamous cell carcinoma and no/little history of smoking is mandatory. Multiplex molecular platforms are preferred to sequential molecular testing since they are less time- and tissue-consuming. In this review, we present the latest updates on the nine most common actionable driver alterations in nonsmall cell lung cancer. Liquid biopsy, a simple noninvasive technique that uses different analytes, mostly circulating tumour DNA, is an appealing tool that is used in thoracic oncology to identify driver alterations including resistance mutations. Additional roles are being evaluated in clinical trials and include monitoring the response to treatment, screening for lung cancer in high-risk patients and early detection of relapse in the adjuvant setting. In addition, liquid biopsy is being tested in immune-oncology as a prognostic, predictive and pharmacodynamic tool. The major limitation of plasma-based assays remains their low sensitivity when compared to tissue-based assays. Ensuring the clinical validity and utility of liquid biopsy will definitely optimise cancer care.
Contemporary issues in the implementation of lung cancer screening
Stephen Lam, Martin Tammemagi
doi : 10.1183/16000617.0288-2020
European Respiratory Review 30 (161) 200288
Lung cancer screening with low-dose computed tomography can reduce death from lung cancer by 20–24% in high-risk smokers. National lung cancer screening programmes have been implemented in the USA and Korea and are being implemented in Europe, Canada and other countries. Lung cancer screening is a process, not a test. It requires an organised programmatic approach to replicate the lung cancer mortality reduction and safety of pivotal clinical trials. Cost-effectiveness of a screening programme is strongly influenced by screening sensitivity and specificity, age to stop screening, integration of smoking cessation intervention for current smokers, screening uptake, nodule management and treatment costs. Appropriate management of screen-detected lung nodules has significant implications for healthcare resource utilisation and minimising harm from radiation exposure related to imaging studies, invasive procedures and clinically significant distress. This review focuses on selected contemporary issues in the path to implement a cost-effective lung cancer screening at the population level. The future impact of emerging technologies such as deep learning and biomarkers are also discussed.
Ventilatory efficiency in athletes, asthma and obesity
Sophie ?. Collins, Devin B. Phillips, Andrew R. Brotto, Zahrah H. Rampuri, Michael K. Stickland
doi : 10.1183/16000617.0206-2020
European Respiratory Review 30 (161) 200206
During submaximal exercise, minute ventilation (V?E) increases in proportion to metabolic rate (i.e. carbon dioxide production (V?CO2)) to maintain arterial blood gas homeostasis. The ratio V?E/V?CO2, commonly termed ventilatory efficiency, is a useful tool to evaluate exercise responses in healthy individuals and patients with chronic disease. Emerging research has shown abnormal ventilatory responses to exercise (either elevated or blunted V?E/V?CO2) in some chronic respiratory and cardiovascular conditions. This review will briefly provide an overview of the physiology of ventilatory efficiency, before describing the ventilatory responses to exercise in healthy trained endurance athletes, patients with asthma, and patients with obesity. During submaximal exercise, the V?E/V?CO2 response is generally normal in endurance-trained individuals, patients with asthma and patients with obesity. However, in endurance-trained individuals, asthmatics who demonstrate exercise induced-bronchoconstriction, and morbidly obese individuals, the V?E/V?CO2 can be blunted at maximal exercise, likely because of mechanical ventilatory constraint.
Impact of ageing and pregnancy on the minute ventilation/carbon dioxide production response to exercise
Michele R. Schaeffer, Jordan A. Guenette, Dennis Jensen
doi : 10.1183/16000617.0225-2020
European Respiratory Review 30 (161) 200225
Ventilatory efficiency can be evaluated using the relationship between minute ventilation (V?E) and the rate of CO2 production (V?CO2). In accordance with the modified alveolar ventilation equation, this relationship is determined by changes in dead space volume (VD) and/or the arterial CO2 tension (PaCO2) equilibrium point. In this review, we summarise the physiological factors that may account for normative ageing and pregnancy induced increases in V?E/V?CO2 during exercise. Evidence suggests that age-related increases in VD and pregnancy-related decreases in the PaCO2 equilibrium point are mechanistically linked to the increased V?E/V?CO2 during exercise. Importantly, the resultant increase in V?E/V?CO2 (ratio or slope), with normal ageing or pregnancy, remains below the critical threshold for prognostic indication in cardiopulmonary disease, is not associated with increased risk of adverse health outcomes, and does not affect the respiratory system's ability to fulfil its primary role of eliminating CO2 and maintaining arterial oxygen saturation during exercise.
Ventilatory efficiency in pulmonary vascular diseases
Jason Weatherald, Brianne Philipenko, David Montani, Pierantonio Laveneziana
doi : 10.1183/16000617.0214-2020
European Respiratory Review 30 (161) 200214
Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation (V?E) relative to carbon dioxide output (V?CO2), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these patients. The mechanisms of ventilatory inefficiency are multiple and include high physiologic dead space, abnormal chemosensitivity and an altered carbon dioxide (CO2) set-point. A normal V?E/V?CO2 makes a pulmonary vascular disease such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) unlikely. The finding of high V?E/V?CO2 without an alternative explanation should prompt further diagnostic testing to exclude PAH or CTEPH, particularly in patients with risk factors, such as prior venous thromboembolism, systemic sclerosis or a family history of PAH. In patients with established PAH or CTEPH, the V?E/V?CO2 may improve with interventions and is a prognostic marker. However, further studies are needed to clarify the added value of assessing ventilatory inefficiency in the longitudinal follow-up of patients.
Tuberous sclerosis complex for the pulmonologist
Yasmine Rebaine, Mouhamad Nasser, Barbara Girerd, Caroline Leroux, Vincent Cottin
doi : 10.1183/16000617.0348-2020
European Respiratory Review 30 (161) 200348
Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either the TSC1 or TSC2 gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions. LAM is a multisystem disorder characterised by cystic destruction of lung parenchyma, and may occur in either the setting of TSC (TSC-LAM) or sporadically (S-LAM). LAM occurs in 30–40% of adult females with TSC at childbearing age and is considered a nonmalignant metastatic neoplasm of unknown origin. TSC-LAM is generally milder and, unlike S-LAM, may occur in males. It manifests as multiple, bilateral, diffuse and thin-walled cysts with normal intervening lung parenchyma on chest computed tomography. LAM is complicated by spontaneous pneumothoraces in up to 70% of patients, with a high recurrence rate. mTOR inhibitors are the treatment of choice for LAM with moderately impaired lung function or chylous effusion. MMPH, manifesting as multiple solid and ground-glass nodules on high-resolution computed tomography, is usually harmless with no need for treatment.
