Interleukin-27 inhibits vaccine-enhanced pulmonary disease following respiratory syncytial virus infection by regulating cellular memory responses.

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also led to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. Interleukin-27 (IL-27) and IL-23 regulate Th1, Th17, and/or Th2 cellular immune responses. In this study, mice coimmunized with pcDNA3-IL-27 and G1F/M2 were fully protected and, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2-, and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice coimmunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2-, and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses and, in particular, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses.

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma.

Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract illness in infants and young children worldwide. The mechanism is largely unknown. RSV stimulates airway epithelial cells and resident leukocytes to release cytokines. Cytokines and chemokines involved in host response to RSV infection are thought to play a central role in the pathogenesis. In addition, RSV infection early in life has been associated with the development of asthma in later childhood. It is likely that the persistence of cytokines and chemokines in fully recovered patients with RSV in the long term can provide a substratum for the development of subsequent asthma. This review describes the genetic factors in cytokines and chemokines associated with severity of RSV disease, cytokines and chemokines synthesis in RSV infection, and the role of these innate immune components in RSV-associated asthma.

Respiratory Nurses Have Positive Attitudes But Lack Confidence in Advance Care Planning for Chronic Obstructive Pulmonary Disease: Online Survey.

Chronic obstructive pulmonary disease (COPD) is a progressive, life-limiting illness. Despite significant symptom burden, access to advance care planning (ACP) and palliative care are limited. Early initiation of ACP enables patients to articulate the values that underpin the decisions they would make if, in the future, they are unable to speak for themselves. Nurses constitute the majority of health care workforce and are well placed to initiate these discussions. This study explored knowledge, attitudes, and practice regarding ACP for patients with COPD among Australian and New Zealand respiratory nurses. A cross-sectional online survey tested knowledge about ACP and canvassed attitudes about current practice. Data were analyzed using descriptive statistics and content analysis of text data. The 112 participating respiratory nurses had substantial knowledge and positive attitudes regarding ACP in COPD; however, they lacked confidence and clarity regarding their role. Despite advances in end-of-life care provision for chronic disease, well-established barriers remained (inadequate training, fear of distressing patients, and time), and discussion triggers were still linked to acute deterioration, diagnosis of severe disease, and patient initiation. Better articulating the role of the respiratory nurse in ACP and building capacity and confidence within this workforce may improve ACP access for people living with COPD.

Pattern recognition receptors for respiratory syncytial virus infection and design of vaccines.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants and young children. Host immune response has been implicated in both the protection and immunopathological mechanisms. Pattern recognition receptors (PRRs) expressed on innate immune cells during RSV infection recognize the RSV-associated molecular patterns and activate innate immune cells as well as mediate airway inflammation, protective immune response, and pulmonary immunopathology. The resident and recruited innate immune cells play important roles in the protection and pathogenesis of an RSV disease by expressing these PRRs. Agonist-binding PRRs are the basis of many adjuvants that are essential for most vaccines. In the present review, we highlight recent advances in the innate immune recognition of and responses to RSV through PRRs, including toll-like receptors (TLRs), retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). We also describe the role of PRRs in the design of RSV vaccines.