PubMed Health⌕ Search

Biomedical subjects

P J Helms

Publications and source records attributed to P J Helms.

At least 19 recordsLinked to original sources
PubMed2004

Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography.

The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P < 0.001); respective relationships for change after bronchodilator were r = 0.09 (ns) and r = 0.64 (P < 0.001). FEF50 also correlated significantly with Rint (R = 0.769, P < 0.001) but not with T(PTEF)/T(E). FEV1 and FEF50 both increased postbronchodilator, with respective mean changes of 11.4% and 28% (P < 0.001), while Rint decreased by 24.3% (P < 0.001). No significant changes were noted for T(PTEF)/T(E). T(PTEF)/T(E) derived from inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.

Age Factors↗
PubMed2004

Eosinophil activation and cysteinyl leukotriene production in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: It has been suggested that acute infantile bronchiolitis associated with respiratory syncytial virus (RSV) may share some pathogenic features with atopic asthma in that virus-specific IgE is produced and cysteinyl leukotrienes (cLTs) and eosinophil cationic protein (ECP) have been detected in airway secretions. ECP is a specific marker of eosinophil activation although leukotrienes can be released from a variety of cells including mast cells, eosinophils and monocytes. OBJECTIVE: To test the association between eosinophil activation and cysteinyl leukotriene production in the upper airway secretions of infants with RSV positive (RSV+ve) bronchiolitis. METHODS: Nasal lavage samples were performed in 78 infants (0.0-11.5 months) admitted to hospital with RSV+ve bronchiolitis soon after admission (0-48 h). Leukotriene C4 (LTC4) was assayed by enzyme immunoassay (EIA) and eosinophil cationic protein (ECP) by fluoroimmunoassay (FIA). RESULTS: LTC4 was detectable in 51 and ECP in 57 of 78 samples with a significant positive relationship between LTC4 and ECP (r=0.557, P<0.001). CONCLUSION: In the majority of our subjects with RSV+ve bronchiolitis ECP and LTC4 were detectable in upper airway secretions and were significantly associated with each other. In this clinical setting much of the detected LTC4 within upper airway secretions is likely to originate from the eosinophil, an observation that may have implications for clinical management and for delineation of the underlying mechanisms associated with this illness.

Blood Proteins↗
PubMed2004

Higher incidence of SIDS at weekends, especially in younger infants.

BACKGROUND: An increased incidence of sudden infant death syndrome (SIDS) at weekends has been previously noted, although it has not been found in all studies. Where a weekend effect has been found it is most prominent on Sundays. AIM: To identify the magnitude of this effect in British data before and after the fall in prevalence associated with the "back to sleep" campaign. METHODS: Aggregated data from England Wales, Scotland, and Northern Ireland for the years 1986-98 during which there were 12,762 deaths from SIDS were examined. RESULTS: Comparing the periods before (1986-90) and after (1993-98) the fall in incidence associated with the "back to sleep" campaign, the percentage of infants dying at the weekend in the later period (32.24%) was slightly greater than for the earlier period (31.30%), although this difference was not statistically significant. In both periods the observed weekend incidences were significantly higher than the expected weekend percentage of 28.6%. Although the proportion of infants aged < or =4 months and > or =5 months at death did not change between the two periods, the weekend effect was more marked in the younger infants, particularly in the 1993-98 period. There was no consistent Saturday effect. In 1993-98 deaths appeared to be more evenly distributed throughout the week for infants > or =5 months. CONCLUSION: The excess of SIDS at weekends still appears to be present despite the overall fall in prevalence associated with the "back to sleep" campaign. Increased risks at weekends might have implications for support to high risk families.

Age Factors↗
PubMed2003

Association of CCR5Delta32 with reduced risk of childhood but not adult asthma.

BACKGROUND: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5Delta32 mutation on asthma and allergy in the transition from childhood to adulthood. METHODS: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5Delta32 status was also characterised and the association with childhood and adulthood symptoms determined. RESULTS: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5Delta32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% CI 0.14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the same population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5Delta32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status. CONCLUSIONS: In a population with a high allelic frequency for the CCR5Delta32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

Adult↗
PubMed2002

Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.

BACKGROUND: The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. OBJECTIVE: An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. METHODS: Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. RESULTS: There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. CONCLUSION: It is concluded that Th1- and Th2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th2-mediated inappropriate responses to non-pathological antigens.

Adolescent↗
PubMed2001

Normal values for phrenic nerve latency in children.

Data derived from detailed studies of normal phrenic nerve latency in a large group of children are presented. They highlight the major differences between the three previously published studies of normal children. Phrenic nerve latency shows a curvilinear relationship with age, averaging 6.0 ms at 0-6 months, falling to 4.8 ms between 1 and 2 years, then rising to 6.3 ms between 10 and 18 years of age. These data represent the largest published study on normal phrenic nerve latency in children.

Adolescent↗
PubMed2001

Genetic/environmental determinants of adult chronic obstructive pulmonary disease and possible links with childhood wheezing.

Epidemiological evidence and similarities in underlying inflammatory mechanisms suggest that childhood respiratory conditions and adult onset chronic obstructive pulmonary disease (COPD) may have a common aetiology. The prevalence of COPD in the UK has been estimated to be 10% in males and 11% in females, and like asthma, is thought to have a polygenic contribution with a complex interplay between genetic and environmental factors. The only proven genetic factor so far identified in its pathogenesis is alpha1-antitrypsin deficiency, although this accounts for less than 1% of individuals with disease. Environmental exposures are significant but the observation that only 15% of smokers develop COPD and only some young children exposed in utero develop recurrent wheezing points to as yet undefined contributory genetic factors. The similarity in response to medication also suggests some features in common and a central question must be whether those adults who develop COPD had transient viral-associated wheeze (VAW) or non-specific bronchial hyperresponsiveness (BHR) in childhood? Similarities between some of the childhood wheezing syndromes and adult onset COPD invites a re-examination of possible links between the two conditions.

Adolescent↗
PubMed2001

Guest editorial.

Explore the source record for details and available documents.

Adolescent↗
PubMed2001

Parents' quality of life and respiratory symptoms in young children with mild wheeze. EASE Study Group.

The Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), measures the impact of child asthma symptoms on family activity (CGAct) and parental anxiety (CGEmot). It has not been validated for families of children <7 yrs, with wheezing illness. This study assessed the sensitivity of the PACQLQ to symptom change in 62 preschool children with wheezing illness. The median age of children was 3 yrs (range 0.8-6 yrs). At entry and 3-month follow-up, parents recorded child respiratory symptoms in a 1-month diary and completed the PACQLQ. On average, children in the study had 7 symptomatic days per month. On entry, mothers < or = 30 yrs had worse scores than those > 30 (p < 0.02), and mothers in less affluent socioeconomic groups had worse scores than those in higher groups (p = 0.05). Change in symptom scores and symptom free days between entry and follow-up was associated with change in PACQLQ scores (r = 0.54-0.57, p <0.001). Thirty-three parents had absolute change in PACQLQ of <0.5 over three months (which has been previously defined as not being clinically significant). Compared to parents with higher PACQLQ change, parents with PACQLQ scores <0.5, did not differ in frequency of child symptoms or in social-demographic factors, but had better quality of life scores on entry to the study (p<0.01). It is concluded that the Paediatric Asthma Caregiver's Quality of Life Questionnaire is sensitive to group measures of child symptom change over 3 months, among preschool children, and this supports its use as an outcome measure in clinical trials. The absolute impact of child symptoms on parent quality of life varies among parents.

Adult↗
PubMed2001

Issues in pediatric asthma.

Different wheezing syndromes can carry the diagnostic label of "asthma," especially in very young children, and an accurate differential diagnosis is essential for improving outcomes. Because presenting symptoms are similar, making a rapid, accurate differential diagnosis is often daunting. Asthma can, eventually, be distinguished from other wheezing disorders based on differences in symptomatology, pathophysiology, and disease evolution. Once diagnosed, inhaled corticosteroids (ICS) remain the cornerstone of treatment in persistent pediatric asthma. Compelling evidence supports the benefits of these agents in reducing asthma-related morbidity and mortality and in preventing airway remodeling. As a result, ICS use in young children with asthma has grown substantially in recent years. Questions are being raised about the appropriateness of early and long-term use of ICS in young children, and whether ICS are overused in this population. Because of the challenges faced by clinicians in differentiating asthma from the other childhood wheezing disorders often present in young children, it may be best to delay the use of regular ICS therapy until a definitive diagnosis can be established. Alternatives to ICS (such as the leukotriene receptor antagonists) should also be considered to avoid the growth-suppressing potential of steroids in the management of mild asthma.

Adrenal Cortex Hormones↗
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↗