Research Research Digest Research Digest 29/01/21 Welcome to the 62nd Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. A hierarchical logistic regression predicting rapid respiratory rates from post-exertional malaise Author: Cotler J, Katz BZ, Reurts-Post C, Vermeulen R, Jason LA (DePaul University, USA)Publication: Fatigue: Biomedicine, Health & BehaviorLink: https://www.tandfonline.com/doi/abs/10.1080/21641846.2020.1845287?journalCode=rftg20 Past research indicates that ME/CFS patients have high rates of hyperventilation. While hyperventilation is commonly associated with psychological factors such as anxiety or somatisation, tachypnea (rapid respiratory rates) is commonly associated with asthma and chronic pulmonary conditions. In this study, researchers examined the possible predictors of tachypnea (rapid respiratory rates) in ME/CFS.A total of 216 adults were involved and participants underwent a two-day cardiopulmonary exercise test (CPET). Participants’ resting respiratory rates were measured on both day one and day two of the CPET and participants answered a series of questionnaires to assess the relationship between tachypnea and various possible factors including post-exertional malaise (PEM).On the first day, 72 participants (32.9%) met the criteria for tachypnea. On the second day, 65 (30.1%) met the criteria. The difference between the two days was not significant, meaning that participants’ tacypnea characterisation was consistent across the two days of the CPET. Hierarchical logistic regression found that PEM was a good predictor of tachypnea, whereas psychological/somatic assessments and sedentary behaviours were not significantly predictive of tachypnea.The authors acknowledge that the limitations of their study include a lack of activity logging, making it difficult to fully determine the contribution of a sedentary lifestyle on respiratory rates, and not confirming the diagnostic criteria used by the participants' physicians. The findings suggest respiratory rates may be used as an objective clinical measurement of PEM. A Literature Review of GP Knowledge and Understanding of ME/CFS: A Report from the Socioeconomic Working Group of the European Network on ME/CFS (EUROMENE) Authors: Pheby DFH, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin J, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X (University of Warwick, UK)Publication: MedicinaLink: https://www.mdpi.com/1010-660X/57/1/7/htm Previous research by these authors revealed significant under-diagnosis of ME/CFS by GPs, resulting in an underestimation of both the prevalence of the condition and its economic impact. In this literature review, the authors examined GP knowledge and understanding of ME/CFS. A total of 30 papers were included, the majority from the UK. The heterogenous nature of the methodologies employed did not allow for a metanalysis to be conducted.The results from papers which surveyed GPs showed that a third to half of those surveyed did not accept ME/CFS as a genuine clinical entity, and more than half lacked confidence to diagnose or manage the condition.Studies which surveyed patients’ experiences with GPs found only a third reported that their GP had experience with ME/CFS, and less than a quarter reported that their GP knew enough to be able to treat their condition. Up to two-thirds of patients surveyed reported feeling dissatisfied with the primary care they received and that their GP needed better education about ME/CFS.These results were consistent across the papers in the review, which were published over a 14-year period, suggesting these issues are long-standing and have changed very little over time.The authors conclude that this widespread disbelief and lack of knowledge and understanding of ME/CFS among GPs results in delayed diagnosis, increasing the risk of severe or prolonged disease. These factors also hamper accurate estimates of the prevalence and economic impact of ME/CFS. Informatics Inference of Exercise-Induced Modulation of Brain Pathways Based on Cerebrospinal Fluid Micro-RNAs in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Authors: Narayan V, Shivapurkar N, Baraniuk JN (Georgetown University, USA)Publication: Network and Systems MedicineLink: https://www.liebertpub.com/doi/10.1089/nsm.2019.0009 MicroRNAs (miRNAs) play an important role in regulating the gene expression that is responsible for normal development and biological functioning. Aberrant miRNA expression is implicated in many disorders (i.e. cancer, autoimmune diseases, and Alzheimer’s disease) and therefore provide a promising candidate for research into understanding, diagnosing and treating disease. Given that post-exertional malaise (PEM) is one of the cardinal symptoms of ME/CFS, this paper sought to determine how exercise affects global micro-RNA (miRNA) expression in patients with ME/CFS.The authors modelled PEM in 15 ME/CFS patients (Fukuda criteria) by having them perform a submaximal bicycle exercise stress test on two consecutive days. 45 additional ME/CFS patients were rested and served as non-exercised controls. Cerebral spinal fluid was collected via lumbar puncture from all patients and miRNA levels were quantified and analysed.The authors discovered five miRNAs whose levels were significantly reduced in patients experiencing PEM compared to rested controls. Informatic analysis of the downstream pathways and targets of the five miRNA candidates were not entirely conclusive but revealed that their pathways generally related to cell adhesion. Further studies will be required to determine the origin of the measured miRNAs. Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study Authors: Giloteaux L, O’Neal A, Castro-Marrero J, Levine SM, Hanson MR (Cornell University, USA)Publication: Journal of Translational MedicineLink: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02560-0 There has been considerable research into cytokine profiles in ME/CFS although to date this has yielded inconsistent results. These authors previously found that circulating extracellular vesicles (EV) were increased in a number in ME/CFS patients compared to healthy controls. This pilot study aimed to examine the cytokine composition of EVs in ME/CFS patients. The study included 35 ME/CFS patients (diagnosed according to the Fukuda criteria) and 35 healthy, age- and sex-matched controls. Circulating EVs were purified from blood samples, and size and concentration of EVs measured. Samples from a subset of 19 patients and 19 healthy controls were further analysed for levels of 45 cytokines and growth factors. The mean total concentration of EVs was not significantly different between ME/CFS patients and healthy controls although there was a significantly greater concentration of EV particles larger than 130nm in the ME/CFS patients. There were no significant differences in cytokine levels between ME/CFS patients and controls, although the authors note the low power of their study to detect such differences. There were significant cytokine-cytokine correlations which differed between the groups. The authors conclude that cross-sectional study designs may be contributing to the inconsistency found in cytokine studies. They recommend longitudinal studies with larger samples, and subgroup analysis based on illness duration and severity.