Jeffrey Bowden

Neutrophils induce damage to respiratory epithelial cells infected with respiratory syncytial virus

The mechanisms by which respiratory syncytial virus (RSV) infection induces bronchiolitis and airway disease are unclear. The presence of large numbers of polymorphonuclear leukocytes (PMN) in the airways of infants with RSV infection suggests a potential role of PMN in airway injury associated with RSV infection. To investigate the potential role of neutrophils in RSV bronchiolitis, human alveolar type II cells (A549 cells) were infected with different doses of RSV for 6-48 h. A 51Cr-releasing assay was used to measure PMN-induced damage and image analysis was used to determine PMN adhesion and detachment of epithelial cells. The results showed that RSV infection of epithelial cells enhanced PMN adherence in a dose- and time-dependent pattern, RSV infection alone could damage and detach epithelial cells to a limited extent and PMN significantly augmented RSV infection-induced damage and detachment of epithelial cells. These data suggest that respiratory syncytial virus infection of respiratory epithelial cells enhances neutrophil adhesion to the epithelium and that activated neutrophils augment the damage and detachment of epithelium infected with the virus. Polymorphonuclear leukocytes may contribute to the pathogenesis of respiratory syncytial virus airway disease by inducing epithelial damage and cell loss.

The Microvasculature as a Participant in Inflammation

Publisher Summary This chapter emphasizes the increase in endothelial permeability and plasma leakage that occur in the inflammatory response of the airway mucosa. The chapter reviews observations made in experimental models of airway inflammation and in human disease with a particular focus on asthma. Asthma is a respiratory illness characterized by variable and reversible airflow obstruction. In view of the potential clinical importance of edema of the airway mucosa, the chapter reviews the evidence that vascular permeability can increase in the airways of asthmatics, assess the methods that have been used to study this change, and examine evidence that functional disturbances can result from the plasma leakage. This chapter also reviews what has been learned in studies of animal model regarding the mechanism of plasma leakage and the identity of inflammatory mediators that trigger the leakage. The chapter also discusses the experimental evidence showing that plasma leakage can be reversed by anti-asthma drugs. The microvascular endothelium, by regulating the leakage of plasma and the emigration of cells into the airway mucosa, plays a key role in coordinating the inflammatory response of the trachea and bronchi.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations: Treatable traits in severe asthma

A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk.

Australian recommendations for EGFR T790M testing in advanced non–small cell lung cancer

First‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as first‐line therapy in patients with non–small cell lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene. Unfortunately, resistance to these therapies often occurs within 10 months of commencing treatment and is mostly commonly due to the development of the EGFR T790M mutation. Treatment with the third‐generation EGFR TKI, osimertinib can prolong progression free survival in patients with the T790M mutation, so it is important to determine the resistance mechanism in order to plan ongoing therapeutic strategies. Here we review the evidence and make recommendations for the timing of T790M mutation testing, the most appropriate specimens to test and the available testing methods in patients progressing during treatment with first line EGFR TKIs for NSCLC.

Delayed onset of benign pleural effusion following concurrent chemoradiotherapy for inoperable non-small-cell lung cancer.

Chronic benign pleural effusion (BPE) is a rare complication of concurrent chemoradiotherapy (CRT) for inoperable stage IIIA non‐small‐cell lung cancer (NSCLC). This report presents three cases of BPE, the workup to differentiate this benign condition from recurrence of cancer and recommends a pleural biopsy as part of the diagnostic process. These inflammatory exudates often remain indolent, and may not require drainage or surgical intervention. In the absence of clinical, radiological and pathological evidence of recurrent disease, we recommend clinicians manage these patients expectantly, using regular clinical assessment and imaging.

Working while unwell: Workplace impairment in people with severe asthma.

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.