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Biomedical subjects

I J Doull

Publications and source records attributed to I J Doull.

27 records · Page 2Linked to original sources

Descriptive study of cough, wheeze and school absence in childhood.

BACKGROUND: Respiratory symptoms such as cough and wheeze are associated with significant morbidity, including school absenteeism. METHODS: A respiratory questionnaire was sent to the parents of all 5727 children aged 7-9 years of age registered with 95 general practitioners in the Southampton area to determine (a) the prevalence of asthma, cough and wheeze, (b) the effects of respiratory symptoms on school absenteeism, and (c) the use of anti-asthma medication. RESULTS: A total of 4830 parents replied (response rate 86%). The 12 month prevalence of wheeze in the absence of cough was 5.5%, cough in the absence of wheeze was 10.0%, and 7.6% reported cough and wheeze; 15.2% of children had been diagnosed. Of the 4830 who replied, 12.7% were receiving bronchodilators, 0.6% xanthine derivatives, 1.7% sodium cromoglycate, and 4.1% inhaled corticosteroids. In all, 348 (7.2%) children had missed more than five days of schooling in the preceding year for respiratory symptoms, while 43 children (0.9%) had missed more than 20 days of schooling in the preceding year. Of the children who had missed more than five days of schooling, 43% reported cough and wheeze, 33% cough alone, and 16% wheeze alone in the preceding year. Compared with children who coughed, those who wheezed were significantly more likely to be diagnosed as asthmatic and to be receiving bronchodilators or inhaled corticosteroids. CONCLUSIONS: In this study, cough was the most frequently reported symptom amongst children missing more than five days of schooling per year.

Absenteeism↗

Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness.

To investigate genetic factors in asthma and atopy, we sought allelic associations for 12 markers near candidate loci for serum total, immunoglobulin E (IgE), and bronchial hyperresponsiveness (BHR) to inhaled histamine in 131 families comprising 685 individuals, selected randomly without regard to atopy or asthma. Nonparametric linkage and association analyses were performed with the Nonparametric Analysis of Lineage and Association (NOPAR) program, and parametric analyses were performed with the Complex Inheritance with Diathesis and Severity (COMDS) program on an ordered polychotomy of ranked scores. On chromosome 11q, allele 168 at the D11S527 locus was significantly associated with BHR (p<0.0003) but not with log IgE. At the D11S534 locus, allele 235 was significantly associated with log IgE (p = 0.007) but not with BHR. Both D11S527 and D11S534 were too distant from the gene encoding the high-affinity IgE receptor FcepsilonRIbeta to account for the association. At the interleukin-9 (IL-9) locus, the 118 allele showed significant association with serum total IgE (p<0.003) but not with histamine BHR. Parametric tests are more conservative, perhaps because they demand consistency with mendelian inheritance and tight linkage. These findings provide support for the view that both chromosomes 5 and 11 may contain genes relevant to asthma and atopy, a possible candidate being the interleukin-4 (IL-4) gene cluster. Because these associations are extremes in a large number of tests, they require confirmation in other samples.

Adolescent↗

Bloodspot cortisol in mild asthma: the effect of inhaled corticosteroids.

Bloodspot cortisol, where finger pricked blood is applied to blotting paper, is suitable for repeated measurements in the home environment. The use of bloodspot cortisol measurements in children with asthma and the effect of inhaled corticosteroids on daytime cortisol concentrations were assessed. Twenty children with mild asthma were randomised to receive double blind either placebo or beclomethasone dipropionate 200 micrograms twice daily. Blood was taken by finger prick at home on waking, and treatment administered. Blood was then taken one hour after treatment, at lunchtime, and in the evening. The area under the curve (AUC) for the four time points was calculated as a composite index of daytime cortisol. Mean (SEM) bloodspot cortisols fell progressively over the day from 199.2 (15.6) nmol/l to 58.4 (8.9) nmol/l. Cortisol in the group treated with beclomethasone dipropionate was lower at all time points, but was significant only after treatment (mean (SEM) 120.9 (14.3) v 177.5 (21.0) nmol/l) and at lunchtime (mean (SEM) 82.7 (12.4) v 128.9 (12.6) nmol/l). AUC for the beclomethasone dipropionate treated group was also significantly decreased (mean (SEM) 317 (31.4) v 446 (29.7)). Beclomethasone dipropionate at a dose of 400 micrograms/day significantly suppresses the daytime cortisol profile.

Administration, Inhalation↗

Reliability of infant length measurement.

The reliability of length measurement was determined in 38 infants less than 1 year of age. The SD of a single length measurement was 0.28 cm at birth and 0.42 cm both at 6 weeks and at 8 months of age, comparable with the SD of a single height measurement in previously reported older children. There is no technical reason to prevent reliable measurement of young infants.

Age Factors↗

Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate.

Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.

Administration, Inhalation↗

Effect of regular inhaled beclomethasone on exercise and methacholine airway responses in school children with recurrent wheeze.

The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA) in the previous 12 months, performed a methacholine challenge and exercise test on separate days at monthly intervals. The subjects had not received oral or inhaled corticosteroids for 12 months prior to the study. The dose-response relationship to inhaled methacholine was expressed as the cumulative dose provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following maximal exercise. Following the first methacholine challenge and exercise test, the children were randomized in a double-blind manner to receive inhaled beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or a placebo b.i.d. from a Diskhaler for 3 months. All children were asymptomatic at the time of testing, and there was no significant change in the baseline FEV1 of any subject prior to either challenge throughout the study period. When compared to placebo, the bronchial responsiveness to exercise and methacholine was significantly attenuated in the children who had received inhaled BDP for at least 1 month. There was no relationship between the bronchial responsiveness to methacholine and exercise. There was no significant difference in the bronchial responsiveness to either stimulus in the atopic and nonatopic children. The results of this study suggest that immunoglobulin E (IgE)- and non-IgE-mediated airway inflammation are important in exercise- and methacholine-induced bronchoconstriction in children with recurrent wheeze, although it is probable that different mechanisms are responsible.

Administration, Inhalation↗

Intraosseous infusion for resuscitation.

An 11 week old infant who had a cardiac arrest secondary to gastrointestinal haemorrhage and was successfully treated using intraosseous infusion is reported. The child was discharged with no apparent neurological deficit.

Bone Marrow↗