Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2020
ReviewImmunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer-A Stimulating Partnership.
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. ⋯ Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.
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Over the past 10 years, there has been substantial progress in the study and implementation of lung cancer screening using low-dose computed tomography (LDCT). The National Lung Screening Trial, the recently reported NELSON (NEderlands-Leuvens Longkanker Screenings ONderzoek) trial, and other European trials provide strong evidence for the efficacy of LDCT to reduce lung cancer mortality. ⋯ In this article, the authors discuss the evolution and current state of the evidence for LDCT screening for lung cancer. The authors will also review the associated risks, cost, and challenges of implementation of an LDCT screening program.
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Semin Respir Crit Care Med · Apr 2020
ReviewNew Developments in the Pathogenesis of Pulmonary Cysts in Birt-Hogg-Dubé Syndrome.
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in Folliculin gene (FLCN). BHD is characterized by lower lobe-predominant pulmonary cysts with risk of pneumothorax, benign skin tumors (fibrofolliculomas), and renal cell carcinoma, often of an unusual chromophobe/oncocytic hybrid histology. The FLCN protein functions in multiple signaling and metabolic pathways including positive regulation of mechanistic target of rapamycin complex 1 (mTORC1) activity via FLCN's GTPase (GAP) activity for Rag C, positive regulation of Wnt signaling (in mesenchymal cells), and negative regulation of TFE3 nuclear localization. ⋯ Folliculin also has functions in autophagy, mitochondrial biogenesis, cell-cell adhesion, 5' AMP activated protein kinase activity, and other pathways. The specific contributions of these pathways to the lung manifestations of BHD are largely unknown. This review is focused on the pulmonary manifestations of BHD, highlighting selected recent advances in elucidating the cellular functions of FLCN and current hypotheses related to the pathogenesis of cystic lung disease in BHD, including the "stretch hypothesis." We also discuss important knowledge gaps in the field, including the genetic, cellular and physical mechanisms of cyst pathogenesis, and the timing of cyst initiation, which may occur during lung development.
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Semin Respir Crit Care Med · Apr 2020
ReviewClinical Decision-Making in Hypersensitivity Pneumonitis: Diagnosis and Management.
This review provides an updated approach to the diagnosis and management of hypersensitivity pneumonitis (HP). The importance of using a multidisciplinary discussion to increase diagnostic and treatment confidence is emphasized. ⋯ Therapeutically, beyond antigen avoidance and newly available antifibrotic therapy for patients with a progressive fibrosing phenotype; the role, timing, and expected response to anti-inflammatory therapy in individual patients are unanswered questions. Since the evidence and validation of testing generally performed during the diagnostic work-up and longitudinal monitoring of HP is feeble at best, the viewpoints discussed are not intended to resolve current controversies but rather to provide a conceptual framework for evaluating discordant information when evaluating and caring for patients with HP.
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Lymphangioleiomyomatosis (LAM) is a slow albeit progressive rare neoplastic disease featured with diffuse thin-walled cysts in lungs and angiomyolipomas in kidneys. LAM affects almost exclusively women and has one of the strongest gender predispositions of any extragenital human disease. Two forms of LAM present clinically, sporadic (S-LAM) and tuberous sclerosis complex-associated (TSC-LAM). ⋯ Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Therapies targeting female sex hormones have shown preclinical efficacy in animal and cell culture-based experiments, but have not been properly investigated clinically. In this review, we summarize current recommendations in the diagnosis and treatment of LAM.