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Biomedical subjects

W Lenney

Publications and source records attributed to W Lenney.

At least 19 recordsLinked to original sources

Preschool healthcare utilisation related to home oxygen status.

OBJECTIVE: To determine, in prematurely born children who had bronchopulmonary dysplasia (BPD), if respiratory morbidity, healthcare utilisation, and cost of care during the preschool years were influenced by use of supplementary oxygen at home after discharge from the neonatal intensive care unit. DESIGN: Observational study. SETTING: Four tertiary neonatal intensive care units. PATIENTS: 190 children, median gestational age 27 weeks (range 22-31), 70 of whom received supplementary oxygen when discharged home. INTERVENTIONS: Review of hospital and general practitioner records together with a parent completed respiratory questionnaire. MAIN OUTCOME MEASURES: Healthcare utilisation, cost of care, cough, wheeze, and use of an inhaler. RESULTS: Seventy children had supplementary oxygen at home (home oxygen group), but only one had a continuous requirement for home oxygen beyond 2 years of age. There were no significant differences in the gestational age or birth weight of the home oxygen group compared with the rest of the cohort. However, between 2 and 4 years of age inclusive, the home oxygen group had more outpatient attendances (p = 0.0021) and specialist attendances (p = 0.0023), and, for respiratory problems, required more prescriptions (p<0.0001). Their total cost of care was higher (p<0.0001). In addition, more of the home oxygen group wheezed more than once a week (p = 0.0486) and were more likely to use an inhaler (p<0.0001). CONCLUSIONS: Children with BPD who have supplementary oxygen at home after discharge have increased respiratory morbidity and healthcare utilisation in the preschool years.

Birth Weight↗

Asthma severity and atopy: how clear is the relationship?

BACKGROUND: The relationship between asthma severity and atopy is complex. Many studies have failed to show significant relationships between clinical severity or lung function and markers of atopic sensitisation. AIM: To determine whether increasing asthma severity is related to atopic sensitisation in a population of children with asthma. METHODS: A total of 400 children (7-18 years) with asthma were recruited as part of a multicentre study of the genetics of asthma. Detailed phenotypic data were collected on all participants. Associations between measures of asthma severity and atopic sensitisation were sought using multilevel models allowing variation at the individual and family level. RESULTS: Children recruited to the study had a range of asthma severities, with just over a third having mild persistent asthma. The logarithm of total serum IgE was associated with increased asthma severity score, decreased FEV1, increased airways obstruction, risk of hospital admission, and inhaled steroid use. Increasing skin prick test reactivity to a panel of seven aeroallergens was associated with increased risk of hospital admission, use of an inhaled steroid, and airways obstruction. The results remained highly significant after corrections for age, gender, and birth order. CONCLUSIONS: In children with asthma, increasing atopy is associated with increasing asthma severity. However, the relationships between asthma severity and skin prick tests, and asthma severity and total serum IgE values, appear subtly different.

Adolescent↗

Regional variation of airway hyperresponsiveness in children with asthma.

Families with asthmatic children were recruited to take part in a multi-centre collaborative study into the genetics of asthma. Detailed phenotypic information was collected on all family members including: lung function, anthropomorphic measurements, response to methacholine challenge, skin prick testing, serum IgE measurements and a detailed nurse-administered questionnaire. Families were eligible for entry into the study if they had two children with a doctor-diagnosis of asthma. Bennett/Twin nebulisers were supplied to each centre from a single source and these were calibrated to determine gravimetric nebuliser output prior to use. Asthmatic probands from each centre had similar degrees of asthma severity and atopy. There was no significant difference in the sex ratios or ages of the probands or numbers of parents with a history of smoking in the families recruited at each centre. However, there was a significant difference in the number of children with airway hyperresponsiveness, with 90% of the North Staffordshire group but only 60% of the Sheffield group having a PC20 of <8 mg/ml for methacholine. This difference highlights the difficulty of using families from different centres in genetic and epidemiological studies.

Asthma↗

Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families.

RATIONALE: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma. OBJECTIVES: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma. METHODS: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models. RESULTS: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values. CONCLUSIONS: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.

Adolescent↗

Maternal glutathione S-transferase GSTP1 genotype is a specific predictor of phenotype in children with asthma.

Maternal factors are known to influence the heritability and expression of asthma and atopy. We report the association of maternal, paternal and proband GSTP1 genotype with lung function in 145 Caucasian children with asthma. GSTP1 Val105/Val105 and Ala114/Val114 genotypes in the child were associated with non-significant increases in lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio). Paternal genotype had no influence on lung function in the child. In contrast, maternal GSTP1 Val105/Val105 genotype was significantly associated with offspring lung function and was strongly predictive of FEV1/FVC (Val105/Val105 105.2%, Ile105/Val105 and Ile105/Ile105 97.9% p=0.006) and maternal GSTP1 Ala114/Val114 genotype was associated with significantly higher FEV1 (Ala114/Val114 109.0%, Ala114/Ala114 99.0% p=0.008), and FEV1/FVC ratios (Ala114/Val114 104.1%, Ala114/Ala114 98.2% p=0.04). The associations between maternal GSTP1 Val105/Val105 genotype and FEV1/FVC and maternal GSTP1 Ala114/Val114 genotype and FEV1 remained significant (p=0.003 and p=0.007) after correction for child and maternal atopic status, passive smoke exposure, smoking during pregnancy, individual and paternal GSTP1 genotype and was independent of transmission to the child. These data support the hypothesis that maternal GSTP1 genotype can act as a specific risk factor which has ex utero consequences for children with asthma. As a child's genotype is not independent of maternal genotype, effects seen in candidate gene studies may be due at least in part to this phenomenon.

Adolescent↗

Health care utilisation of prematurely born, preschool children related to hospitalisation for RSV infection.

BACKGROUND: In prematurely born infants with chronic lung disease (CLD), RSV hospitalisation is associated with increased health service utilisation and costs in the first two years after birth. AIMS: To determine whether RSV hospitalisation in the first two years was associated with chronic respiratory morbidity during the preschool years in prematurely born children who had had CLD. METHODS: Retrospective review of readmissions, outpatient attendances, and community care in years 2-4 and, at age 5 years, assessment of the children's respiratory status and their health related quality of life. Comparison was made of the results of children who had had at least one hospitalisation in the first two years after birth for RSV infection (RSV group) to those of the rest of the cohort. Participants were 190 of an original cohort of 235 infants with CLD and a median gestational age 27 (range 22-33) weeks. RESULTS: The 33 children in the RSV group, compared to the rest of the cohort, had a greater duration of hospital stay and more outpatient appointments. The RSV group had required more prescriptions for all treatments and respiratory medications, and more had used an inhaler. The cost of care of the RSV group was higher (median 2630 pounds sterling [4000 Euros, US4800 dollars], range 124-18,091 pounds sterling versus 1360 pounds sterling [2500 Euros, US3000 dollars], range 5-18 929 pounds sterling ) and their health related quality of life was lower. CONCLUSION: In prematurely born children who had developed CLD, RSV hospitalisation in the first two years was associated with chronic respiratory morbidity and increased cost of care.

Ambulatory Care↗

Further support for the association of CCR5 allelic variants with asthma susceptibility.

English and German nuclear families containing multiple asthmatic children and asthmatic parents were analysed to retest a recently reported association between resistance to asthma and the delta32 allele of chemokine receptor 5 (CCR5). Analysis of the families by the transmission-disequilibrium test (TDT) revealed a non-significant trend in the English families that provided marginal confirmation of the association (P < 0.125), but no similar trend was observed in the German families. Case-control comparison of delta32 allele and genotype frequencies in asthmatic vs. non-asthmatic parents revealed a significantly lower frequency of delta32 in asthmatic English parents (P < 0.009) and a similar but non-significant trend in German parents (P < 0.265). Taken together, the pattern of results provides confirmation for the previously observed delta32-asthma association and indicates that susceptibility to asthma may be influenced by CCR5 or another gene in chromosomal region 3p21.

Alleles↗

HPA-axis effects of nebulised fluticasone propionate compared with oral prednisolone in childhood asthma.

The aim of this study was to compare the effect of 7 days nebulised fluticasone propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion, systemic exposure and safety. This was a randomised, double-blind, double-dummy, two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8 years) with stable asthma were randomly assigned to 7 days treatment with either FP Nebules (2 x 0.5 mg/2 ml bd) or prednisolone tablets once daily (2 mg/kg/day for 4 days [maximum 40 mg] followed by 1 mg/kg/day or half the original dose for 3 days [maximum 20 mg]). After a 2-4 week washout period, patients received the second treatment for 7 days, followed by a 2-week follow-up visit. The primary outcome measure was 24-h urinary-free cortisol concentrations corrected for creatinine. Nebulised FP (1 mg bd) had significantly less effect on 24-h urinary-free cortisol excretion than oral prednisolone (8.9 ng/ml for FP and 5.0 ng/ml for prednisolone, P = 0.001). Systemic exposure to FP was also low. In conclusion, FP Nebules had significantly less effect on hypothalamic-pituitary-adrenal axis function than oral prednisolone in asthmatic children when used at doses recommended for the treatment of an acute exacerbation of asthma.

Administration, Inhalation↗

Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease.

OBJECTIVES: To determine whether the rehospitalisation and primary care requirements of infants with chronic lung disease (CLD) during the first two years after birth were influenced by a requirement for supplementary oxygen after discharge from the neonatal intensive care unit. METHODS: Review of records from both the hospital and general practitioner. PATIENTS: 235 infants, median gestational age 27 (range 22-31) weeks, 88 of whom were receiving supplementary oxygen when discharged home. RESULTS: Overall, the infants required a median of 2 (range 0-20) admissions per patient, 8 (0-41) outpatient attendances, 13 (0-76) contacts with the general practitioner, and 17 (0-169) consultations with other primary healthcare professionals. The home oxygen patients required significantly more and longer admissions (p < 0.01) and more outpatient attendances (p < 0.05). The total cost of care per infant of the home oxygen group was greater (p < 0.001); this reflected higher costs for hospital stay (p < 0.01), total inpatient care (p < 0.01), and primary care drugs (p < 0.01). CONCLUSION: Despite routine use of antenatal steroids and postnatal surfactant, certain patients with CLD, particularly those who receive home oxygen treatment, show high rates of utilisation of health service resources after discharge from the neonatal care unit.

Analysis of Variance↗

Inhaler devices for asthma: do we follow the guidelines?

BACKGROUND: Despite national guidelines for asthma treatment, many children have troublesome symptoms. AIM: To assess the extent to which the use of inappropriate inhaler devices contributes to this problem. METHODS: Of 14 813 questionnaires distributed to schoolchildren, 6996 (47%) were returned identifying 1444 children using asthma inhalers. Inhalers were categorised as age appropriate or inappropriate according to national guidelines and were compared with those used by 75 patients attending a hospital clinic. RESULTS: A total of 35% of "schools" and 4% of "clinic" children reported using an inappropriate inhaler device. Most were using metered dose inhalers alone. Twenty four per cent of "schools" children < or = 5 years old did not use a spacer. Both children and parents overestimated the child's ability to use their inhaler. CONCLUSIONS: Large numbers of children are given inhalers they cannot use. To improve asthma care we must ensure that prescriptions reflect the age and ability of the child. Recent recommendations by the Department of Health in England and Wales stress the importance of seamless care between primary and secondary services. As the management of childhood asthma is guided primarily by secondary care providers, it is therefore imperative that general paediatricians know the difficulties and issues which are occurring in the community. This will enable them to lead and support necessary change.

Administration, Inhalation↗

Guest editorial.

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Journal Article↗

Pseudomonas aeruginosa in cystic fibrosis: cross-infection and the need for segregation.

Evidence-based reasons for segregation of patients colonized with Pseudomonas aerugionsa in the outpatient setting are unclear. To clarify local decisions, Pseudomonas genotyping of the local environment, patients and patient contacts was undertaken in 1993. The hospital environment was re-swabbed in 1997. Pseudomonas genotyping of old and new patients attending the North Staffordshire cystic fibrosis clinic has subsequently been undertaken and more recently been repeated on an annual basis to assess whether the same Pseudomonas genotypes can be found in both the environment and in patients, and whether the same Pseudomonas genotype can be transferred from one patient to another. No Pseudomonas genotype found in the local environment in 1993 or in 1997 has been found in any of our patients. Nine children attending the same special school for many years and sharing the same physiotherapy facilities showed no evidence of cross-infectivity. Except for siblings living in the same household our cross-infectivity rate is very low and where cross-infection has potentially occurred the level of contact between these patients has been minimal. This study does not support the suggestion that patients with cystic fibrosis attending the North Staffordshire clinic and colonized with Pseudomonas aeruginosa should be segregated from non-colonized patients.

Adolescent↗

Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection.

AIMS: To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. METHODS: Review of community care, outpatient attendances, and readmissions in the first two years after birth. PATIENTS: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. RESULTS: The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. CONCLUSION: RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

Analysis of Variance↗

How should airways resistance be measured in young children: mask or mouthpiece?

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (MicroRint) obtained using a mouthpiece were compared with those using a face mask. Fifty children aged 4-7 yrs performed four sets of six Rint measurements; two using a mouthpiece and two using a face mask with integral mouthpiece. Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. Mean Rint values obtained using the mouthpiece were significantly lower than those using the face mask ((mean+/-SD) mouthpiece=0.81+/-0.18 kPa x L(-1) x s, mask=0.88+/-0.24 kPa x L(-1) x s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa x L(-1) x s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p = 0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice. Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.

Child↗