Associations between outdoor fungal spores and childhood and adolescent asthma hospitalisations.

BACKGROUND: Childhood asthma is a significant public health problem and severe exacerbations can result in diminished quality of life and hospitalisation. OBJECTIVE: To examine the contribution of outdoor fungi to childhood and adolescent asthma hospitalisations. METHODS: The Melbourne Air Pollen Children and Adolescent (MAPCAH) study is a case-crossover study of 644 children and adolescents (aged 2-17 years) hospitalised for asthma. MAPCAH collected individual data on human rhinovirus (HRV) infection and sensitisation to Alternaria and Cladosporium; and daily counts of ambient concentrations of fungal spores, pollen and air pollutants. Conditional logistic regression models were used to assess associations with increases in spore counts while controlling for potential confounding and testing interactions. RESULTS: Exposure to Alternaria (aOR=1.07, 95%CI 1.03-1.11), Leptosphaeria (aOR=1.05, 95%CI 1.02-1.07), Coprinus (aOR=1.04, 95%CI 1.01-1.07), Drechslera (aOR=1.03, 95%CI1.00-1.05) and total spores (aOR=1.05, 95%CI 1.01-1.09) were significantly associated with child asthma hospitalisations independent of HRV infection. There were significant lagged effects up to 3-days with Alternaria, Leptosphaeria, Cladosporium, Sporormiella, Coprinus, and Drechslera. Some of these associations were significantly greater in participants with Cladosporium sensitisation. CONCLUSION: Exposures to several outdoor fungal spore taxa, including some not reported in previous research, are associated with the risk of child and adolescent asthma hospitalisation, particularly in individuals sensitised to Cladosporium. We need further studies to examine cross-reactivity causing asthma exacerbations. Identifying sensitisation to multiple fungal allergens in asthmatic children could support the design and implementation of more effective strategies to prevent asthma exacerbations.

Impact of genetic polymorphisms determining leukocyte/neutrophil count on chemotherapy toxicity

Nous avons investigué la relation entre les polymorphismes de nucléotides simples (SNPs) chez trois gènes/loci candidats : DARC, CXCL2 et le loci ORMDL3-GSDMA-CSF3 situés sur le chromosome 17q21 et les complications neutropéniques et infectieuses qui en résultent durant la chimiothérapie chez les patients atteints de la leucémie lymphoblastique aigue. Ces loci codent pour certaines composantes du système immunitaire altérant la concentration de chémokines et leur distribution (DARC), stimulant le relâchement et la migration des neutophiles de la moelle épinière (CXCL2) et régulant la prolifération et la survie des granulocytes (G-CSF). Il est possible que des polymorphismes dans ces loci lorsqu’associés à de la chimiothérapie puissent mettre des individus suceptibles à un risque plus élevé de complication reliées à la chimiothérapie. Une sélection des marqueurs SNPs dans ces gènes ont été génotypés chez des enfants traités au CHU Ste-Justine pour une ALL entre 1989 et 2005. Après correction pour tests multiples, un polymorphisme DARC rs3027012 situé dans le 5’UTR a été associé à un compte phagocytaire peu élevé (APC<500 et <1000 cellules/µL, p=0.001 and p=0.0005, respectivement) ainsi qu’une hospitalisation due à une neutropénie (p=0.007) ou due à une infection et/ou neutropénie (p=0.007). Un effet protecteur a été identifié pour la mutation non sense Gly42Asp variant rs12075 (p=0.006). Des polymorphismes sur le chromosome 17q2 étaient associés à une hospitalisation due à une infection (rs3859192, p= 0.004) et à une neutropénie (rs17609240, p=0.006) L’infection était aussi modulée par CXCL2 (rs16850408, p=0.008) Cette étude identifie pour la première fois que les loci modulant le décompte des leucocytes et des neutrophiles pourraient jouer un rôle dans de déclenchement de complications dues à la chimiothérapie et pourraient ainsi servir de marqueurs pour un ajustement et un suivi du traitement.

Impact of genetic polymorphisms determining leukocyte/neutrophil count on chemotherapy toxicity

Nous avons investigué la relation entre les polymorphismes de nucléotides simples (SNPs) chez trois gènes/loci candidats : DARC, CXCL2 et le loci ORMDL3-GSDMA-CSF3 situés sur le chromosome 17q21 et les complications neutropéniques et infectieuses qui en résultent durant la chimiothérapie chez les patients atteints de la leucémie lymphoblastique aigue. Ces loci codent pour certaines composantes du système immunitaire altérant la concentration de chémokines et leur distribution (DARC), stimulant le relâchement et la migration des neutophiles de la moelle épinière (CXCL2) et régulant la prolifération et la survie des granulocytes (G-CSF). Il est possible que des polymorphismes dans ces loci lorsqu’associés à de la chimiothérapie puissent mettre des individus suceptibles à un risque plus élevé de complication reliées à la chimiothérapie. Une sélection des marqueurs SNPs dans ces gènes ont été génotypés chez des enfants traités au CHU Ste-Justine pour une ALL entre 1989 et 2005. Après correction pour tests multiples, un polymorphisme DARC rs3027012 situé dans le 5’UTR a été associé à un compte phagocytaire peu élevé (APC<500 et <1000 cellules/µL, p=0.001 and p=0.0005, respectivement) ainsi qu’une hospitalisation due à une neutropénie (p=0.007) ou due à une infection et/ou neutropénie (p=0.007). Un effet protecteur a été identifié pour la mutation non sense Gly42Asp variant rs12075 (p=0.006). Des polymorphismes sur le chromosome 17q2 étaient associés à une hospitalisation due à une infection (rs3859192, p= 0.004) et à une neutropénie (rs17609240, p=0.006) L’infection était aussi modulée par CXCL2 (rs16850408, p=0.008) Cette étude identifie pour la première fois que les loci modulant le décompte des leucocytes et des neutrophiles pourraient jouer un rôle dans de déclenchement de complications dues à la chimiothérapie et pourraient ainsi servir de marqueurs pour un ajustement et un suivi du traitement.

The inter-rater reliability of the Risk Instrument for Screening in the Community

Predicting risk of adverse healthcare outcomes is important to enable targeted delivery of interventions. The Risk Instrument for Screening in the Community (RISC), designed for use by public health nurses (PHNs), measures the one-year risk of hospitalisation, institutionalisation and death in community-dwelling older adults according to a five-point global risk score: from low (score 1,2), medium (3) and high (4,5). We examined the inter-rater reliability (IRR) of the RISC between student PHNs (n=32) and expert raters using six cases (two low, medium and high-risk), scored before and after RISC training. Correlations increased for each adverse outcome, statistically significantly for institutionalisation (r=0.72 to 0.80,p=0.04) and hospitalisation, (r=0.51 to 0.71,p<0.01) but not death. Training improved accuracy for low-risk but not all high-risk cases. Overall, the RISC showed good IRR, which increased after RISC training. That reliability reduced for some high-risk cases suggests that the training programme requires adjustment to further improve IRR.

Cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. Due to ageing of the general population and improved survival from cardiac disease the prevalence of heart failure is rising. Despite the fact that the majority of patients with heart failure are aged over 65 years old, many with multiple co-morbidities, the association between cognitive impairment and heart failure has received relatively little research interest compared to other aspects of cardiac disease. The presence of concomitant cognitive impairment has implications for the management of patients with heart failure in the community. There are many evidence based pharmacological therapies used in heart failure management which obviously rely on patient education regarding compliance. Also central to the treatment of heart failure is patient self-monitoring for signs indicative of clinical deterioration which may prompt them to seek medical assistance or initiate a therapeutic intervention e.g. taking additional diuretic. Adherence and self-management may be jeopardised by cognitive impairment. Formal diagnosis of cognitive impairment requires evidence of abnormalities on neuropsychological testing (typically a result ≥1.5 standard deviation below the age-standardised mean) in at least one cognitive domain. Cognitive impairment is associated with an increased risk of dementia and people with mild cognitive impairment develop dementia at a rate of 10-15% per year, compared with a rate of 1-2% per year in healthy controls.1 Cognitive impairment has been reported in a variety of cardiovascular disorders. It is well documented among patients with hypertension, atrial fibrillation and coronary artery disease, especially after coronary artery bypass grafting. This background is relevant to the study of patients with heart failure as many, if not most, have a history of one or more of these co-morbidities. A systematic review of the literature to date has shown a wide variation in the reported prevalence of cognitive impairment in heart failure. This range in variation probably reflects small study sample sizes, differences in the heart failure populations studied (inpatients versus outpatients), neuropsychological tests employed and threshold values used to define cognitive impairment. The main aim of this study was to identify the prevalence of cognitive impairment in a representative sample of heart failure patients and to examine whether this association was due to heart failure per se rather than the common cardiovascular co-morbidities that often accompany it such as atherosclerosis and atrial fibrillation. Of the 817 potential participants screened, 344 were included in this study. The study cohort included 196 patients with HF, 61 patients with ischaemic heart disease and no HF and 87 healthy control participants. The HF cohort consisted of 70 patients with HF and coronary artery disease in sinus rhythm, 51 patients with no coronary artery disease in sinus rhythm and 75 patients with HF and atrial fibrillation. All patients with HF had evidence of HF-REF with a LVEF <45% on transthoracic echocardiography. The majority of the cohort was male and elderly. HF patients with AF were more likely to have multiple co-morbidities. Patients recruited from cardiac rehabilitation clinics had proven coronary artery disease, no clinical HF and a LVEF >55%. The ischaemic heart disease group were relatively well matched to healthy controls who had no previous diagnosis of any chronic illness, prescribed no regular medication and also had a LVEF >55%. All participants underwent the same baseline investigations and there were no obvious differences in baseline demographics between each of the cohorts. All 344 participants attended for 2 study visits. Baseline investigations including physiological measurements, electrocardiography, echocardiography and laboratory testing were all completed at the initial screening visit. Participants were then invited to attend their second study visit within 10 days of the screening visit. 342 participants completed all neuropsychological assessments (2 participants failed to complete 1 questionnaire). A full comprehensive battery of neuropsychological assessment tools were administered in the 90 minute study visit. These included three global cognitive screening assessment tools (mini mental state examination, Montreal cognitive assessment tool and the repeatable battery for the assessment of neuropsychological status) and additional measures of executive function (an area we believe has been understudied to date). In total there were 9 cognitive tests performed. These were generally well tolerated. Data were also collected using quality of life questionnaires and health status measures. In addition to this, carers of the study participant were asked to complete a measure of caregiver strain and an informant questionnaire on cognitive decline. The prevalence of cognitive impairment varied significantly depending on the neuropsychological assessment tool used and cut-off value used to define cognitive impairment. Despite this, all assessment tools showed the same pattern of results with those patients with heart failure and atrial fibrillation having poorer cognitive performance than those with heart failure in sinus rhythm. Cognitive impairment was also more common in patients with cardiac disease (either coronary artery disease or heart failure) than age-, sex- and education-matched healthy controls, even after adjustment for common vascular risk factors.