The very first Breathing Together Journal Club took place on 22nd February 2019. Since we are spread out all over the UK, we had a teleconference-style journal club.
Journal clubs are commonly held in research groups around the world. JCs allow us to get together and review publications to learn what others are working on; helping us stay up to date. On this occasion, we had two papers for discussion.
For the first paper, we were lucky to have Prof Turner, the first author himself, to present.
Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze.
Turner S, Miller D, Walsh GM, Scaife A, Power UF, Shields MD, Devereux G.
Pediatr Pulmonol. 2018 Jan;53(1):10-16. doi: 10.1002/ppul.23915. Epub 2017 Nov 14.
The first paper we talked about reported outcomes from a study where cells were taken from the inside of babies noses within two days of birth. The cell properties were compared between those babies who later went on to wheeze at the age of four years and those who had no asthma symptoms by four years of age.
The researchers grew the cells using what is now an old method called “submerged culture”, where the cells grow on the bottom of a tiny dish and on top of these cells is a thin layer of liquid media which gives the cells nutrients and also collects things made by the cells. The researchers measured in the layer of fluid a number of things that the cells produced. Many of the things measured (molecules called cytokines and chemokines, which act as messengers between cells) have been linked to asthma in other studies. Parents of the babies were contacted when their child was four years old, and 120 of the 139 replied to say whether their child did or did not have wheeze.
The main finding was that production of a cytokine called interleukin-8 (thought to be important to causing the irritation in the breathing tubes, also called airway inflammation) was less in the cells from the 11 babies who went on to have wheeze compared to those who did not wheeze. Not all babies with low interleukin-8 production had wheeze, but no babies with high interleukin-8 production went on to wheeze.
This study suggests that when babies are born, having low interleukin-8 production in cells lining their breathing tubes may be a predisposition to later asthma symptoms. Additional factors may be needed for the low interleukin-8 level to be linked to later asthma symptoms. It is likely that cytokines and chemokines in addition to interleukin-8 will be important. We hope that Breathing Together, with its much larger number of babies and more thorough testing of babies, can take these preliminary findings to a much higher level.
For the second paper Piotr and Charlotte, PhD students at the University of Edinburgh, jointly presented.
Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze.
Turi KN, Shankar J, Anderson LJ, Rajan D, Gaston K, Gebretsadik T, Das SR, Stone C, Larkin EK, Rosas-Salazar C, Brunwasser SM, Moore ML, Peebles RS Jr, Hartert TV.
Am J Respir Crit Care Med. 2018 Oct 15;198(8):1064-1073. doi: 10.1164/rccm.201711-2348OC.
Respiratory Syncytial Virus (RSV) acute respiratory infection during infancy increases the risk for recurrent wheeze and asthma. In this paper, the authors attempted to identify the classes of molecules that are being produced in response to RSV infection (immune responses), which might be associated with recurrent wheeze. Researchers recruited healthy infants at birth and followed their respiratory health throughout the first year. Immune responses were assessed in the nasal cavity of infants that suffered from acute respiratory RSV infection. Those infants were then followed for two years; any recurrent wheeze episodes were recorded.
Utilizing specialized self-learning algorithms, the authors looked at the different immune molecules produced in the nose and they were identified two distinct immune response patterns to RSV. One of these patterns, characterized by high production of inflammatory mediators and low production of non-interferon mediators (interferons are molecules essential for antiviral responses) was associated with recurrent wheeze while the other pattern was not. A similar immune response to rhinovirus (cause of most “common cold” infections) was not associated with recurrent wheeze.
This discovery, if confirmed by other large-scale studies, has the potential to help explain why there is such a strong association between asthma and RSV infection. The study is also helpful to Breathing Together researchers as it highlights molecules that might be involved in asthma development. This might help with better planning of experiments.
Photo courtesy of Ralph Hodgson, Imperial College London.