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Biomedical subjects

P J Helms

Publications and source records attributed to P J Helms.

At least 37 records · Page 2Linked to original sources
PubMed2001

Early environmental influences in the development of asthma and atopic disease.

Intrauterine and early life exposures are important contributors to allergic sensitisation and to the subsequent expression of allergic disease and asthma. The recent epidemic of asthma and atopy clearly underlines the strength of environmental factors such as respiratory and enteric infections, allergen exposure, diet and lifestyles including exposure to cigarette smoke. These and other as yet unidentified environmental contributors are also likely to interact with underlying genetic predisposition. Although recent research interest has focussed on host responses and priming of TH2 lymphocytes there are some paradoxes yet to be resolved. What are the determinants of "homing" of sensitisation to the airway and does persistent airway inflammation result in airway remodelling or are these features independent risk factors for persistence and disease? Evidence that environmental exposures in fetal life and infancy influence lifelong respiratory health remains controversial. However it is becoming apparent that a range of environmental exposures and conditions do influence the development of asthma and atopic disease and that whole population interventions aimed at primary prevention might soon become realistic.

Adolescent↗
PubMed2000

Issues and unmet needs in pediatric asthma.

Asthma is common and becoming more so in childhood. Although mild asthma may incur low average annual costs per child, these estimates need to be viewed in the context of the very large numbers of affected individuals. Whereas asthma and wheezing illness in childhood had in the past been broadly subdivided into asthma (often associated with atopy) and wheezy bronchitis (wheeze only, with associated upper respiratory tract infection), this distinction was lost during the 1970s in view of the demonstrated underdiagnosis and undertreatment of symptomatic school-age children. The acceptance of asthma as a chronic inflammatory disease and evidence for airway remodeling and progressive deterioration in airway function in association with symptoms and atopy have led to earlier use of topical steroids at higher starting doses delivered by improved age-appropriate devices. Treating all children as if they were destined to become atopic asthmatics and at risk of airway remodeling may not be rational, particularly in those whose symptoms will subsequently resolve. However, there are as yet no screening tests which can clearly identify individuals at risk of long-term chronic airway inflammation and airway remodeling. The large number of infants and young children with current symptoms suggestive of asthma and in whom resolution is likely in the majority poses problems for the clinician in deciding the best initial therapy. There is an urgent need to develop simple and reliable measures that can identify the early manifestations of atopic airway sensitisation and to establish the place of early intervention with nonsteroidal drugs, including leukotriene antigonists.

Airway Obstruction↗
PubMed2000

Early introduction of inhaled steroids in wheezing children presenting in primary care. A pilot study. EASE Study Group.

BACKGROUND: Recurrent wheezing illness in childhood is a frequent reason for consultation in both primary and secondary care and whilst there is widespread support for the earlier introduction of inhaled corticosteroids (ICS) concerns remain about potential adverse systemic effects. OBJECTIVE: We sought to identify the feasibility and size of study required to assess the benefits, adverse effects and cost-effectiveness of early introduction of ICS. METHODS: We entered 86 children (mean age 4.5 years) with at least two consecutive wheezing episodes into a pragmatic randomized controlled trial. All children were already being prescribed beta2-agonist and those allocated to ICS were prescribed twice daily beclomethasone dipropionate 200 microg or budesonide 200 microg. At entry and 3 and 6 months age appropriate lung function (FEV(1), T(ptef):T(e)), respiratory symptoms, quality of life of children and carers, growth and sexual maturation, bone mass and bone turnover, and health care costs were assessed. RESULTS: Drop out rate was 8% (7 of 86). No significant differences were found in FEV(1) or T(ptef):T(e) at 6 months. Respiratory symptoms and health-related quality of life of children and carers improved equally in both groups. No significant differences were found in growth rates or in bone mass. In the ICS group markers of bone turnover (Pyd:Cr) fell (271 vs 237 nmol/mmol) in contrast to a rise in those on beta(2) alone (255 vs 319 nmol/mmol) P < 0.05. Combined health care costs were higher in the ICS group. CONCLUSIONS: The low drop out rate provided evidence that the protocol was practical and acceptable. In order to confirm these results, and using the same study design, power estimates indicated that 260 children would need to be randomized.

Administration, Inhalation↗
PubMed2000

Corticosteroid-sparing options in the treatment of childhood asthma.

During the last 30 years, a significant rise in wheezing illness has occurred in the child population. Despite its high prevalence there is no clear definition of the disease, which includes a heterogeneous group of syndromes ranging from transient wheezing in infancy to atopic asthma with persistence into adult life. Molecular advances and further epidemiological information from well characterised individuals and their families are likely to clarify the different subtypes of wheezing illness and inform therapeutic options. With the recognition that chronic airway inflammation is a feature of persistent disease, at least in adults, there has been a trend towards the early introduction of anti-inflammatory treatment and particularly inhaled corticosteroids (ICS). However, the natural resolution of much wheezing illness, particularly in young children and in children with viral-induced episodes, suggests that newly presenting children should remain on symptomatic therapy alone while the severity of the disease is being assessed. Although ICS have become a cornerstone of management of chronic persistent disease, their ability to protect against exacerbations in young and mildly affected children is questionable. Alongside concerns about long term use of ICS and possible systemic adverse effects, there remains a need for alternative approaches to the control of the disease in children. Extrapolation of the findings of large multicentre adult studies into childhood, particularly for doubling the doses of ICS and long-acting beta2-agonists, may be unsound. Other approaches include the early introduction of inhaled cromones, use of second generation antihistamines, low dose theophyllines and, more recently, leukotriene modifiers. As the majority of preschool children will become asymptomatic by mid-childhood, there is an urgent need to identify those in whom chronic airway inflammation is developing, as it is in this group that early introduction of ICS may be of maximum benefit. In the remainder, other approaches, including use of corticosteroid-sparing longacting P2-agonists and leukotriene modifying drugs, may be more appropriate. Safe and effective oral preparations such as leukotriene modifying drugs are likely to establish a significant role in the management of symptoms in children of all ages and with all types of asthma and wheezing illness.

Adrenal Cortex Hormones↗
PubMed2000

Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

OBJECTIVES: (1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study. DESIGN: A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months. SETTING: Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice. SUBJECTS: Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness. INTERVENTIONS: Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed. MAIN OUTCOME MEASURES: (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues. RESULTS: Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups. CONCLUSIONS: Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Adolescent↗
PubMed2000

Respiratory morbidity in primary care. A population based study, using practices from the Scottish Continuous Morbidity Recording Research Database.

OBJECTIVE: To elucidate the patterns and period prevalences of respiratory disease with special reference to asthma (including wheezing) in view of its increasing reported prevalence. DESIGN: Observational study based on prospectively entered data. SETTING/SUBJECTS: Fifty five Continuous Morbidity Recording (CMR) practices with 290,000 patients located throughout Scotland. RESULTS: Respiratory problems accounted for a large proportion (17%) of total general practice workload. Upper respiratory tract infections were the commonest presentation in pre-school children, followed by asthma but with an ever increasing proportion of consultations for bronchitis and lower respiratory tract infections with advancing adult age. There was no significant correlation between deprivation and the incidence of asthma. CONCLUSIONS: Observed rates and patterns of disease for CMR practices, were similar to previously reported studies. The large number of presentations by patients in early childhood with minor respiratory illnesses and in particular upper respiratory tract infections are likely to reflect a heightened level of parental anxiety where interpretation of clinical signs and separation of simple and significant illness can be difficult. CMR has also been shown to be of use in helping to investigate links between deprivation and disease incidence or severity. Potential uses for CMR include the study of whole population morbidity and utilisation of primary care services.

Database Management Systems↗
PubMed1999

Association of CCR5 delta32 with reduced risk of asthma.

We report that individuals carrying the CCR5 delta32 mutation, a naturally occurring variant of the C-C chemokine receptor 5 (CCR5), are at reduced risk of developing asthma. These data suggest a possible explanation for the high prevalence of this mutation in the general population.

Adolescent↗
PubMed1999

Development and integration of CAL: a case study in medicine.

CONTEXT: The Faculty of Medicine and Medical Sciences at the University of Aberdeen viewed the use of Computer Assisted Leaning (CAL) and other IT based learning resources as a possible way of coping with an increase in student numbers whilst maintaining or increasing the quality of medical teaching. OBJECTIVES: Our primary objective was to develop and integrate Computer Assisted Learning (CAL) applications into the undergraduate medical curriculum. SUBJECTS/MATERIALS: A wide spectrum of CAL applications were developed dealing with many topics in the curriculum. METHODS: We formulated a structured approach to CAL development by establishing a team of professionals (forming a CAL Unit), using existing expertise and by implementing a process to ensure that the CAL had a maximum impact upon the curriculum. The CAL included multimedia tutorials, learning guides, computer aided assessment (CAA) and Model Patients. RESULTS: There are now over 150 IT based learning resources in our curriculum and course evaluation has showed that these have been well received by students. CONCLUSIONS: We conclude that with the wise use of the many skills and facilities usually available within an institution and by promoting collaborative projects with others, the production of high quality CAL is possible within most institutions.

Computer-Assisted Instruction↗
PubMed1999

Influence of socioeconomic conditions on growth in infancy: the 1921 Aberdeen birth cohort.

OBJECTIVES: To identify environmental influences on infant growth using data from a birth cohort established in 1921. DESIGN: A longitudinal cohort study. SETTING: Aberdeen 1921-22. SUBJECTS: Five hundred and sixteen individuals (263 boys and 253 girls) born in Aberdeen during 1921. Health visitor assessments ranged from two to 40 (47% received at least 10 visits). No records were available for infants who died. Individuals were grouped as those who did not breast feed, those who breast fed initially but not at 6 months, and those who were continuing to breast feed at 6 months. MAIN OUTCOME MEASURE: Rate of weight gain over the 1st year of life. A random effects model was used to identify environmental factors and conditions contributing to rate of weight gain in the 1st year of life. RESULTS: Breast feeding rates were about 80% and 50% at 10 days and 6 months, respectively. Breast fed infants were significantly heavier than bottle fed infants at 28 days but this difference disappeared by 12 months. Significant negative effects on rate of weight gain, independent of initial body weight, were found for overcrowding in family homes and maternal parity, whereas social class had no effect. CONCLUSION: Studies based on historical cohorts that have controlled socioeconomic variables only in terms of social class (derived from parental occupation) may have been subject to residual confounding. Growth in the 1st year of life is likely to reflect a number of environmental influences, some of which may continue to have effects throughout early life and beyond.

Aged↗
PubMed1999

Asthma, wheezy bronchitis, and atopy across two generations.

Although the prevalence of asthma has risen significantly during the last 30 yr, it is not clear whether this has occurred primarily in persons with a strong genetic predisposition to asthma and atopy or in other sections of the population. We have investigated outcomes in children of nuclear families selected through probands previously characterized by studies in 1964 and 1989 as having histories of persistent childhood onset atopic asthma, transient childhood wheezy bronchitis, and no respiratory symptoms or atopy. Children of wheezy bronchitic probands had a significantly better symptomatic outcome in adolescence, irrespective of the atopic status of the parent proband, than do children of either asthmatic or asymptomatic probands, suggesting that this may be a syndrome that shows familial aggregation and is distinct from asthma. Total serum IgE levels were significantly lower in children of nonatopic asymptomatic probands, including those with wheezing symptoms. In contrast children of nonatopic asymptomatic probands had an unexpectedly high prevalence of wheezing (33%), positive skin prick tests (56%), and positive specific serum IgE to common allergens (48%) that was similar to that found in children of atopic asthmatic probands. Our findings support the concept that wheezy bronchitis is a separate syndrome from atopic asthma. High total serum IgE levels within our population appear to be an important marker of genetic predisposition to atopy. Our data also suggest that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk of developing asthma or atopy.

Adolescent↗
PubMed1999

Seasonality, but not prevalence of sudden infant death syndrome varies by region in mainland Britain.

This study aimed to investigate whether seasonal variation in day length contributed to winter/summer variation in sudden infant death syndrome (SIDS) at different latitudes in mainland Britain. Over 11 yrs 13,973 deaths were studied. Using appropriate analytic techniques a sine curve was fitted to monthly rates with the amplitude indicating magnitude of seasonal change. The rate of SIDS per 1,000 live births was the same (1.73) in the north as in the south. The amplitude was a quarter less in the north (41.3%) than in the south (54.2%) (p<0.001). While annual rates did not differ, the within year distribution did. The findings for seasonality of SIDS births were similar (amplitudes: north 213%, south 32.3%). Correlations were made between SIDS amplitude and individual environmental factors, particularly temperature and day length. These complex issues, while reported briefly, do not allow firm conclusions. In the north the winter day length is shorter, sunshine hours are less and temperature is lower, but the winter increment in SIDS is less. The extent of seasonal variation of sudden infant death syndrome is greater in the south as compared with the colder, darker north but this has no effect on sudden infant death syndrome rates. Changing photoperiod by latitude, amongst other environmental influences, may hold clues to the aetiology of sudden infant death syndrome.

Humans↗
PubMed1998

Seasonality of sudden infant death syndrome (SIDS) by age at death.

Seasonality of sudden infant death syndrome (SIDS) is a well-established epidemiological finding. The purpose of the study was to determine whether this feature varied significantly with age at death. In total, 13990 cases of SIDS in Scotland, England and Wales during 1982-1992 were studied by age group at death. Seasonality was established by fitting a sinusoidal curve and for each set of monthly data the peak position in the year and its magnitude were determined. Weighted regression revealed significant differences in peak position and amplitude of seasonal variation between those dying at < or = 4 months and those aged > or = 5 months at death. Those infants in the younger age group were more likely to die earlier in the winter months and had a smaller variation in seasonality. The peak (acrophase) months were January for < or = 4 months and February for > or = 5 months at death. Weighted regressions of peak position and amplitude on age at death had p-values of <0.001 and <0.01, respectively. A log linear model relating SIDS incidence to month of birth, month of death and age was able to explain some of these findings. The findings support the hypothesis that in SIDS there may be more than one infant cohort, each of which passes through a vulnerable developmental window at different ages.

Age Factors↗
PubMed1998

Seasonality of sudden infant death syndrome in mainland Britain and Ireland 1985-95.

By the end of 1995 four years had passed since the dramatic fall in the incidence of sudden infant death syndrome (SIDS), following the "back to sleep" campaign. This time lag permitted a more definitive epidemiological reassessment than had been possible before. The extent of seasonal variation from 1992-5 fell by about half, occurring mainly as a single step down in 1992. The fall was relatively greater in winter than in summer. Before 1992 the extent of seasonal variation (amplitude) was greater in those age > or = 5 months compared with those aged < or = 4 months. Since 1992 the falls in incidence and amplitude have been greater in the younger group, suggesting that SIDS deaths in younger and older babies may have different causes.

Age Factors↗
PubMed1998

Is the increase in asthma prevalence occurring in children without a family history of atopy?

We investigated the familial associations of asthma and atopic disease in a population in which the prevalence of asthma and atopy is increasing. Interviewer administered abbreviated family history questionnaires were applied in 416 families with a total of 1005 children ascertained through index children attending fracture and dressing clinics. The prevalence of reported asthma (22.5%), eczema (24%) and hayfever (20%) in the children was high but similar to previous studies in this population. Asthma was reported in 20.8% of children of parents without a history of asthma and 18% of children of parents without any history of atopic disease. Logistic regression analysis of outcomes in the index children showed increased risk of atopic disease associated with parental history of the same atopic disease. The presence of an affected sibling was associated with an increased risk of eczema (OR 3.04 CI 1.83-5.05) or hayfever (OR 1.79 CI 0.97-3.3) but not asthma (OR 1.18 CI 0.66-2.08). Increasing number of siblings was associated with reduced risk although this was significant only for hayfever (OR 0.62 CI 0.41-0.86). Although the presence of affected relatives is associated with an increased risk of atopic disease the high prevalence of reported atopic disease, particularly asthma. in children of parents without a family history of atopic disease suggests that much of the increase in asthma prevalence is occurring in children without a significant genetic predisposition. Childhood asthma developing in what would previously have been regarded as low risk families may differ in its aetiology from classical atopic asthma.

Adult↗