To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma.
Cross-sectional observational study.
The primary care Optimum Patient Care Research Database and the British ...Thoracic Society Difficult Asthma Registry.
Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control).
Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group.
748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified.
Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.
Type 1 diabetes (T1D) incidence in children and adolescents varies widely, and is increasing in many nations. The 10th edition of the International Diabetes Federation Atlas estimated incident cases ...in 2021 for 215 countries/territories (“countries”).
Studies on T1D incidence for young people aged 0–19 years were sourced and graded using previously described methods. For countries without studies, data were extrapolated from similar nearby countries.
An estimated 108,300 children under 15 years will be diagnosed in 2021, a number rising to 149,500 when the age range extends to under 20 years. The ratio of incidence in 15–19 years compared to those aged 0–14 years was particularly high in some countries in sub-Saharan Africa, North Africa/Middle East, and in Mexico.
Only 97 countries have their own incidence data, with extrapolation required for some very populous nations. Most data published were not recent, with 27 countries (28%) having data in which the last study year was 2015 or afterwards, and 26 (27%) having no data after 1999.
Many countries have recent data but there are large gaps globally. Such data are critical for allocation of resources, teaching, training, and advocacy. All countries are encouraged to collect and publish current data.
Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British ...Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.
More infants with bronchopulmonary dysplasia (BPD) now survive to adulthood, but little is known regarding persisting respiratory impairment. We report respiratory symptoms, lung function and ...health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full-term controls. Respiratory symptoms (European Community Respiratory Health Survey) and HRQoL (EuroQol (EQ)-5D) were measured in 72 adult BPD survivors (mean ± sd study age 24.1 ± 4.0 years; mean ± sd gestational age 27.1 ± 2.1 weeks; and mean ± sd birth weight 955 ± 256 g) cared for in the regional neonatal intensive care unit, Royal Maternity Hospital, Belfast, UK (between 1978 and 1993). These were compared with 57 non-BPD controls (mean ± sd study age 25.3 ± 4.0 years; mean ± sd gestational age 31.0 ± 2.5 weeks; and mean ± sd birth weight 1238 ± 222 g) and 78 full-term controls (mean ± sd study age 25.7 ± 3.8 years; mean ± sd gestational age 39.7 ± 1.4 weeks; and mean ± sd birth weight 3514 ± 456 g) cared for at the same hospital. Spirometry was performed on 56 BPD, 40 non-BPD and 55 full-term participants. BPD subjects were twice as likely to report wheeze and three times more likely to use asthma medication than controls. BPD adults had significantly lower forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity than both the preterm non-BPD and full-term controls (all p<0.01). Mean EQ-5D was 6 points lower in BPD adults compared to full-term controls (p<0.05). BPD survivors have significant respiratory and quality of life impairment persisting into adulthood.
Background: Fruit and vegetable (FV) intake, which is often low in older people, is associated with reduced chronic disease risk.Objective: We determined whether increased FV intake improves measures ...of immune function.Design: We conducted a randomized controlled trial (The Ageing and Dietary Intervention Trial) in 83 healthy volunteers aged 65–85 y with low FV intakes (≤2 portions/d); 82 subjects completed the intervention. Participants were assigned to continue their normal diets or to consume ≥5 FV portions/d for 16 wk. At 12 wk, tetanus toxoid (0.5 mL intramuscular) and Pneumovax II vaccine (0.5 mL intramuscular; both vaccines from Sanofi Pasteur) were administered. FV intake was monitored by using diet histories, and biomarkers of nutritional status were assessed. The primary endpoint was the antibody response to vaccination. Specific antibodies binding to tetanus toxoid (total IgG) and pneumococcal capsular polysaccharide (total IgG and IgG2) were assessed at baseline and 16 wk. Participants were recruited between October 2006 and June 2008.Results: The change in FV consumption differed significantly between groups mean change in number of portions (95% CI): in the 2-portion/d group, 0.4 portions/d (0.2, 0.7 portions/d); in the 5-portion/d group, 4.6 portions/d (4.1, 5.0 portions/d); P < 0.001) and also in micronutrient status. Antibody binding to pneumococcal capsular polysaccharide (total IgG) increased more in the 5-portion/d group than in the 2-portion/d group geometric mean (95% CI) of the week 16:baseline ratio: 3.1 (2.1, 4.4) and 1.7 (1.3, 2.1), respectively; P = 0.005). There was no significant difference in the increases in antibody binding to tetanus toxoid.Conclusion: Increased FV intake improves the Pneumovax II vaccination antibody response in older people, which links an achievable dietary goal with improved immune function. This trial was registered at clinicaltrials.gov as NCT00858728.
To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.
Relevant ...studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.
Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little.
The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
Aims/hypothesis
The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published ...literature and performing meta-analyses where possible.
Methods
A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.
Results
In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.
Conclusions/interpretation
This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.
Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity; however, there is little direct trial evidence to support the concept ...that fruit and vegetable consumption improves vascular function. This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension.
After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day, participants were randomized to consume either 1, 3, or 6 portions daily for the next 8 weeks. Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention. Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers. A total of 117 volunteers completed the 12-week study. Participants in the 1-, 3-, and 6-portions/d groups reported consuming on average 1.1, 3.2, and 5.6 portions of fruit and vegetables, respectively, and serum concentrations of lutein and beta-cryptoxanthin increased across the groups in a dose-dependent manner. For each 1-portion increase in reported fruit and vegetable consumption, there was a 6.2% improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine (P=0.03). There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside, an endothelium-independent vasodilator.
The present study illustrates that among hypertensive volunteers, increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis.
Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in ...the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids. The most frequent therapeutic intervention was maintenance oral corticosteroids and most steroid sparing agents (apart from omalizumab) demonstrated minimal steroid sparing benefit. A significant unmet clinical need remains in this group, specifically a requirement for therapies which reduce systemic steroid exposure.
Osteoporosis is a global health issue, and modifiable behavioural factors need to be identified in childhood to reduce the risk of osteoporosis in later life. The aim of this study was to investigate ...the influence of diet and physical activity on bone density of children aged 5–7 years participating in the Belfast Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Family study.
Pregnant women were recruited to the Belfast centre of the HAPO study at 24–32 weeks gestation. Offspring were followed up at 5–7 years as part of the Belfast HAPO Family Study. Heel bone mineral density (BMD) and bone mineral apparent density (BMAD) were measured and calculated, respectively. Physical activity in the offspring was measured by accelerometery and dietary intakes were measured using a 4-day food diary.
Results from 793 offspring were analysed. Mean age of the offspring ± standard deviation was 6.4 ± 0.5 years. A mean of 48.3 ± 22.4 min each day was spent in moderate to vigorous physical activity (MVPA). Median (interquartile range) dietary calcium and vitamin D intakes were 844 (662–1073) mg/day and 1.7 (1.1–2.5) μg/day, respectively. Neither dietary vitamin D nor calcium intakes were significantly associated with offspring heel BMD or BMAD in multiple regression. However, controlling for confounders, a 30-min greater MVPA was associated with significantly larger heel BMD (0.018 g/cm2 in boys and 0.010 g/cm2 in girls) and BMAD (0.005 g/cm3 in boys and 0.003 g/cm3 in girls).
Physical activity was associated with better BMD and BMAD in 5–7-year-old children. Dietary calcium and vitamin D were not predictive of BMD and BMAD.
•The aim was to explore the influence of diet and physical activity on bone mineral density (BMD) of children aged 5-7 years.•Neither dietary vitamin D/calcium intakes were significantly associated with child heel BMD or BMAD in multiple regression.•Physical activity was associated with better BMD and BMAD in 5–7-year-old children.•More research is needed regarding blood concentrations of vitamin D and calcium to determine association with BMD.
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