Therese Burke

Spatial variability in the pollen count in Sydney, Australia: can one sampling site accurately reflect the pollen count for a region?

BACKGROUND There is increasing interest in the daily pollen count, with pollen-sensitive individuals using it to determine medication use and researchers relying on it for commencing clinical drug trials and assessing drug efficacy according to allergen exposure. Counts are often expressed qualitatively as low, medium, and high, and often only 1 pollen trap is used for an entire region. OBJECTIVES To examine the spatial variability in the pollen count in Sydney, Australia, and to compare discrepancies among low-, medium-, and high-count days at 3 sites separated by a maximum of 30 km. METHODS Three sites in western Sydney were sampled using Burkard traps. Data from the 3 sites were used to compare vegetation differences, possible effects of some meteorological parameters, and discrepancies among sites in low-, medium-, and high-count days. RESULTS Total pollen counts during the spring months were 14,382 grains/m3 at Homebush, 11,584 grains/m3 at Eastern Creek, and 9,269 grains/m3 at Nepean. The only significant correlation between differences in meteorological parameters and differences in pollen counts was the Homebush-Nepean differences in rainfall and pollen counts. Comparison between low- and high-count days among the 3 sites revealed a discordance rate of 8% to 17%. CONCLUSIONS For informing the public about pollen counts, the count from 1 trap is a reasonable estimation in a 30-km region; however, the discrepancies among 3 trap sites would have a significant impact on the performance of a clinical trial where enrollment was determined by a low or high count. Therefore, for clinical studies, data collection must be local and applicable to the study population.

Cortical dysfunction underlies disability in multiple sclerosis.

Background: Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance. Objectives: Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS. Methods: Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing–remitting MS patients (RRMS) and 66 controls. Results: Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale. Conclusion: Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.

Allergic Rhinoconjunctivitis in Elite Athletes Optimal Management for Quality of Life and Performance

Allergic rhinoconjunctivitis is a common condition with a peak incidence in the age range of the majority of elite athletes. The condition has been shown to have a significant impact on the quality of life of those affected and poses particular challenges when present in the elite athlete. When an athlete is looking for exceptional performance at events such as the Olympic Games, any factor which affects quality of life by interfering with sleep, decreasing the ability to concentrate, or reducing peak physical fitness, may have a significant impact on the ability to perform at one’s best.Optimal management begins with correct diagnosis and identification of triggering factors.There are a number of therapeutic options available to the treating physician. When formulating a management plan for the elite athlete, the physician must consider ‘doping’ rules and the possible effect of medication on athletic performance.Medication choices include the newer, non-sedating antihistamines, used either orally or topically, and the prophylactic use of intranasal corticosteroids. When allergic conjunctivitis is the principal problem, the newer, topical antihistamines are highly effective and have a rapid onset of action. Since avoidance strategies are rarely practical for the athlete, consideration should be given to strategies such as immunotherapy, where long-term benefit is possible.

Effects of intranasal budesonide on symptoms, quality of life, and performance in elite athletes with allergic rhinoconjunctivitis.

ObjectiveTo assess change in symptoms, quality of life (QOL), and performance ability before, during, and after treatment with budesonide in a group of Olympic and Paralympic athletes with seasonal allergic rhinoconjunctivitis (SAR/C). DesignBecause budesonide has already been proven to be an effective and well-tolerated treatment of SAR/C, 1 an open-label treatment format was used. SettingThe study was community-based with participating athletes preparing for Olympic competition. ParticipantsOlympic and Paralympic athletes were screened for the presence of SAR/C using history and positive skin test results for pollen allergens. InterventionsAll were offered treatment with intranasal budesonide, applied to each nostril, once daily for eight weeks. Outcome MeasurementsSymptom and medication diaries were completed before treatment and after 4 and 8 weeks of treatment. Similarly, Quality of Life (QOL) was measured with the Rhinoconjunctivitis Quality of Life Questionnaire. As a secondary outcome measure, the ability to train and compete was assessed using a performance diary. ResultsOf the 236 athletes eligible for the study, 145 (61%) agreed to participate. Forty-six percent of the athletes who were dispensed treatment did not return questionnaires. For those returning questionnaires, scores between baseline (week 0) and weeks 4 and 8 were calculated for total symptoms, QOL, and performance scores.There were statistically significant improvements in symptoms, QOL, and performance scores in athletes who used intranasal budesonide. ConclusionSAR/C is a common condition and has demonstrable negative effects on athletes. Better education of coaches and athletes is necessary to ensure that the condition is correctly diagnosed and treated, with safe, effective, permitted medication.

The utility of multimodal evoked potentials in multiple sclerosis prognostication

The ability to predict disability development in multiple sclerosis (MS) is limited. While abnormalities of evoked potentials (EP) have been associated with disability, the prognosticating utility of EP in MS remains to be fully elucidated. The present study assessed the utility of multimodal EP as a prognostic biomarker of disability in a cohort of clinically heterogeneous MS patients. Median and tibial nerve somatosensory, visual, and brainstem auditory EP were performed at initial assessment on 63 MS patients (53 relapsing-remitting and 10 secondary progressive) who were followed for an average of 2 years. A combined EP score (CEPS) was calculated consisting of the total number of abnormal EP tests, and was correlated with the Expanded Disability Status Scale (EDSS) at baseline and follow-up. There was a significant correlation between multimodal EP and baseline and follow-up EDSS. Specifically, tibial nerve P37 latencies correlated with EDSS (R(BASELINE)=0.49, p<0.01; R(FOLLOW-UP)=0.47, p<0.01), as did the median nerve N13 (R(BASELINE)=0.40, p<0.01; R(FOLLOW-UP)=0.35, p<0.05) and N20 latencies (R(BASELINE)=0.43, p<0.01; R(FOLLOW-UP)=0.47, p<0.01), and P100 full-field (R(BASELINE)=0.50, p<0.001; R(FOLLOW-UP)=0.45, p<0.001) and central field latencies (R(BASELINE)=0.60, p<0.001; R(FOLLOW-UP)=0.50, p<0.001). In addition, there was a significant correlation between the CEPS with baseline (R=0.65, p<0.001) and follow-up (R=0.57, p<0.01) EDSS. In contrast, white matter disease burden, as measured by T2 lesion load, exhibited a weaker correlation with EDSS (R(BASELINE)=0.28, p<0.05). In conclusion, these findings suggest that abnormalities of EP, as quantified by the novel CEPS, may be a useful biomarker for prognosticating clinical disability in MS, and may aid in the quantification of MS disease severity and in guiding therapeutic decisions.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

Early relapse outcomes in long‐term stable patients switching from interferon β/glatiramer acetate (IFNβ/GA) to oral therapy are unknown.

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

A 7 year pollen profile of major Olympic Games venues in Sydney, Australia

The year 2000 Olympic and Paralympic Games heldin Sydney, Australia were unique in the historyof the Games because they were staged in theearly to mid spring. This led to the concernthat pollen-sensitive athletes may havesignificant problems with allergic symptomstriggered by pollen exposure and that this mayhave compromised their ability to attain theirbest performance. Unfortunately, there was nosystematic pollen count data available for thecity of Sydney up until this time so thepurpose of this study was to obtain a profileof the pattern and type of pollens in theregion so that Olympic team managers andmedical staff could be adequately advised andable to prepare allergic athletes for anyexposures encountered while training andcompeting.We performed pollen monitoring of three majorOlympic venues over the six years before theGames to provide a profile of the mostprevalent species appearing over the spring.The pollen counts obtained at the major siteswere extremely high over the periods oftraining and competition. Tree pollens appearedfrom late July, peaking in August andSeptember, whilst grass pollens appeared fromSeptember and peaked in mid October. Arelatively small number of pollen varietiescomprise the majority of the pollen count.

Differentiating patterns of oligoclonal banding in the cerebrospinal fluid improves diagnostic utility for multiple sclerosis

Background: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is an important adjunct to the diagnosis of multiple sclerosis (MS) and clinically isolated syndromes (CIS). OCBs are considered present if two or more extra IgG bands are present in CSF in comparison to a simultaneously collected serum sample. However, using isoelectric focusing and immunofixation with anti-IgG, we observed two distinct banding patterns, one in which the bands were numerous and prominent (which we termed ‘delta’) and a much more subtle pattern, with fewer, more indistinct bands (‘theta’). Aim: To perform a prospective study to determine the diagnostic implications of the two OCB patterns for multiple sclerosis. Methods: Over a 2-year period, 56 consecutive CSF samples with OCBs were identified. Clinical information and radiological data were collected and correlated with the two banding patterns. Results: Of the 56 positive CSF samples, 46 (82%) demonstrated a delta pattern, and 10 (18%), a theta pattern. The delta pattern was associated with MS/CIS in 34 of 46 (74%) samples, compared with zero of the 10 theta samples (0%, p < 0.001). Exclusion of the theta pattern samples increased the positive predictive value of OCB testing from 61% to 74% for MS/CIS. Conclusion: The diagnostic significance of oligoclonal bands in CSF for MS/CIS can be improved by restricting interpretation to the delta banding pattern alone.

Data characterizing the ZMIZ1 molecular phenotype of multiple sclerosis

The data presented in this article are related to the research article entitled “The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of a molecular phenotype of multiple sclerosis” Fewings et al. (2017) [1]. Here we identify the set of genes correlated with ZMIZ1 in multiple cohorts, provide phenotypic details on those cohorts, and identify the genes negatively correlated with ZMIZ1 and the cells predominantly expressing those genes. We identify the metabolic pathways in which the molecular phenotype genes are over-represented. Finally, we present the flow cytometry gating strategy we have used to identify the immune cells from blood which are producing ZMIZ1 and RPS6.