Expert review of respiratory medicine
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In non-small cell lung cancer (NSCLC), immunotherapy is one of today's most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with ≥25% PD-L1 tumor expression in the EGFR and ALK wild-type population. ⋯ Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.
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Expert Rev Respir Med · Jul 2018
ReviewRecognizing, quantifying and managing patient-ventilator asynchrony in invasive and noninvasive ventilation.
Patient-ventilator asynchrony may occur with modes of partial ventilatory support. Because this problem is associated with worsened outcomes, identifying and managing asynchronies has been recognized as a relevant clinical problem during both invasive and noninvasive (NIV) mechanical ventilation. Areas covered: In this review article, we first describe the different forms of patient-ventilator asynchrony and how they are classified and quantified. ⋯ Finally, we describe the actions that can be undertaken in order to limit the rate of asynchronies during both invasive ventilation and NIV mechanical ventilation, such as modifications of the ventilator mode and/or settings, variation of the sedation regimen (type and doses), and other technical pitfalls. Expert commentary: Detection of asynchronies is crucial in order to reduce their incidence, adopting adjustments of the ventilator settings, sedation regimen, and other technical pitfalls. It remains to be clarified whether the relationship between high incidence of asynchrony and worsened outcome is causative or just associative.
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Expert Rev Respir Med · Jun 2018
ReviewCFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.
Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. ⋯ This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.
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Rigid bronchoscopy is an invaluable tool for the management of airway disorders and an essential skill for an interventional pulmonologist. Since its introduction in the late 19th century, it has remained an important technique for the management of central airway obstruction, foreign body aspiration and massive hemoptysis. Areas covered: This article will review the history, indications, contraindication, technique and complications of rigid bronchoscopy. ⋯ Expert commentary: Although the rise of flexible bronchoscopy in the 1960s led to a decline in the use of rigid bronchoscopy, the last two decades have witnessed resurgence in its popularity. We anticipate that it will remain an important tool used by interventional pulmonologists for decades to come. We suggest that interventional pulmonologists must have training and develop expertise in this technique.
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Expert Rev Respir Med · Jun 2018
ReviewCurrent and emerging techniques for the diagnosis of hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is the result of an immunologically induced inflammation of the lung parenchyma in response to inhalation exposure to a large variety of antigens in genetically susceptible individuals. HP shares clinical and radiological features with other acute and chronic interstitial lung diseases and is sometimes difficult to diagnose if exposure to an antigenic agent is not detected. Several classifications and diagnostic criteria have been proposed but are not currently recommended by guidelines from any scientific society. ⋯ Areas covered: This article will provide a summary of the different classification and diagnostic criteria proposed in acute and chronic forms of HP. In addition, we review current diagnostic procedures including antigen detection, high resolution computed tomography, histopathology and provide an overview of emerging techniques. Expert commentary: Important changes are occurring in the field of HP and knowledge of the disease will likely progress enormously in the coming 5 to 10 years as many techniques continue to be developed, including genomic signature and diagnostic biomarkers.