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Biomedical subjects

J Grigg

Publications and source records attributed to J Grigg.

At least 19 recordsLinked to original sources

Parental understanding of wheeze and its impact on asthma prevalence estimates.

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

Asthma↗

Locally generated particulate pollution and respiratory symptoms in young children.

BACKGROUND: Particulate matter <10 mum (PM(10)) from fossil fuel combustion is associated with an increased prevalence of respiratory symptoms in children and adolescents. However, the effect of PM(10) on respiratory symptoms in young children is unclear. METHODS: The association between primary PM(10) (particles directly emitted from local sources) and the prevalence and incidence of respiratory symptoms was studied in a random sample cohort of 4400 Leicestershire children aged 1-5 years surveyed in 1998 and again in 2001. Annual exposure to primary PM(10) was calculated for the home address using the Airviro dispersion model and adjusted odds ratios (ORS) and 95% confidence intervals were calculated for each microg/m(3) increase. RESULTS: Exposure to primary PM(10) was associated with the prevalence of cough without a cold in both 1998 and 2001, with adjusted ORs of 1.21 (1.07 to 1.38) and 1.56 (1.32 to 1.84) respectively. For night time cough the ORs were 1.06 (0.94 to 1.19) and 1.25 (1.06 to 1.47), and for current wheeze 0.99 (0.88 to 1.12) and 1.28 (1.04 to 1.58), respectively. There was also an association between primary PM(10) and new onset symptoms. The ORs for incident symptoms were 1.62 (1.31 to 2.00) for cough without a cold and 1.42 (1.02 to 1.97) for wheeze. CONCLUSION: In young children there was a consistent association between locally generated primary PM(10) and the prevalence and incidence of cough without a cold and the incidence of wheeze which was independent of potential confounders.

Air Pollution↗

New insights into pulmonary inflammation in cystic fibrosis.

Persistent lower airway infection with inflammation is the major cause of morbidity and mortality in cystic fibrosis. This review examines the recent advances in the understanding of airway inflammation in cystic fibrosis, and focuses on the evidence that pulmonary inflammation is, under some circumstances, disassociated from infection, and the potential implications for therapeutic intervention.

Child↗

Objective perimetry using the multifocal visual evoked potential in central visual pathway lesions.

AIMS: To examine the ability of the multifocal pattern visual evoked potential (mVEP) to detect field loss in neurological lesions affecting the visual pathway from the chiasm to the cortex. METHOD: The mVEPs recorded in the clinic were retrospectively reviewed for any cases involving central neurological lesions. Recordings had been performed with the AccuMap V1.3 objective perimeter, which used an array of four bipolar occipital electrodes to provide four differently oriented channels for simultaneous recording. 19 patients with hemianopias were identified. Of these there were 10 homonymous hemianopias with hemifield type loss, two bitemporal hemianopias, and seven homonymous hemianopias with quadrantanopic distribution. A comparison with subjective field results and CT/MRI findings was done to determine the relation between the two methods of visual field mapping and any relation with the anatomical location of the lesion and the mVEP results. RESULTS: In all hemianopic type cases (12) the defect was demonstrated on the mVEP and showed good correspondence in location of the scotoma (nine homonymous and two bitemporal). The topographic distribution was similar but not identical to subjective testing. Of the seven quadrantanopic type hemianopias, only four were found to have corresponding mVEP losses in the same areas. In the three cases where the mVEP was normal, the type of quadrantanopia had features consistent with an extra-striate lesion being very congruous, complete, and respecting the horizontal meridian. CONCLUSIONS: The mVEP can detect field loss from cortical lesions, but not in some cases of homonymous quadrantanopia, where the lesion may have been in the extra-striate cortex. This supports the concept that the mVEP is generated in V1 striate cortex and that it may be able to distinguish striate from extra-striate lesions. It implies caution should be used when interpreting "functional" loss using the mVEP if the visual field pattern is quadrantic.

Adult↗

Management of paediatric asthma.

Paediatric asthma best practice not only includes prescribing the correct therapeutic mix based on consensus guidelines, but also reducing therapy once control has been achieved. Clinicians should also be aware that asthma in young children is a heterogeneous entity, and a beneficial response to bronchodilators and/or inhaled steroids is not inevitable. In general, preschool children and infants should not be prescribed inhaled corticosteroids above 200 microg beclometasone dipropionate equivalent twice a day, or regular oral steroids, or long acting beta2-adrenoceptor agonists. New therapies such as anti-IgE antibodies are on the horizon, but these are unlikely to replace the established drug combinations. More likely is that the delivery of established drugs will become more convenient (for example, once a day inhaled corticosteroids, or season dependent prophylactic therapy).

Acute Disease↗

Systemic neutrophil activation in acute preschool viral wheeze.

BACKGROUND: In preschool children, attacks of wheeze are usually triggered by viral colds. The inflammatory substrate in preschool viral wheeze (PVW) is unclear, but epidemiological data suggest that most PVW is not caused by allergic inflammation. We therefore speculated that the neutrophils are an important effector cell. Systemic neutrophil activation is the first stage for the development of pulmonary neutrophilia. Markers of neutrophil activation are shedding of the adhesion molecule L-selectin from the cell surface, upregulation of Mac-1 expression, and an increase in serum soluble L-selectin. AIMS: To obtain evidence for systemic neutrophil activation during PVW. METHODS: Preschool children (1-5 years) admitted to hospital with acute PVW (n = 20) and normal controls (n = 18) were studied. Adhesion molecule expression on CD16 positive neutrophils was determined in both groups and expressed as molecules of equivalent fluorochrome (MEF). Serum soluble L-selectin was analysed by ELISA. RESULTS: Compared with controls, children with PVW had reduced neutrophil L-selectin expression (median MEF (IQR): 69 (11 to 96) units versus 136 (109 to 163) units, p < 0.001) and higher serum soluble L-selectin (2.8 (2.3 to 3.1) versus 2.4 (2.2 to 2.6) micro g/ml, p = 0.04). There was no significant difference in neutrophil Mac-1 expression. CONCLUSION: Systemic neutrophil activation is associated with acute PVW.

Acute Disease↗

Penetrating keratoplasty in children: visual and graft outcome.

AIMS: To review factors affecting graft survival and determinants of visual acuity after penetrating keratoplasty in children. METHODS: All cases of penetrating keratoplasty performed in an ophthalmic unit, in children aged less than 15 years at the time of operation, for the period 1984 to 2002 were included. RESULTS: 19 penetrating keratoplasties were done in 18 eyes of 16 children, age range 2 weeks to 14 years 8 months (mean 9.24 years), with mean follow up 6.6 years. 73.7% of grafts have remained clear for up to 14 years. Postoperative visual acuity among congenital indications for graft was better than 6/60 in only 14.2% of cases, but was better than or equal to 6/12 in all cases of keratoconus. CONCLUSION: This series shows that prolonged corneal graft survival can be achieved in children, but successful restoration of visual acuity depends upon a period of normal visual development before the onset of corneal opacification.

Adolescent↗

Eosinophil activation and preschool viral wheeze.

BACKGROUND: A study was undertaken to ascertain whether systemic eosinophil activation is associated with preschool viral wheeze (PVW). METHODS: Urinary eosinophil protein X (uEPX) and serum total IgE (IgE) levels were measured in children admitted to hospital with PVW, and uEPX was measured 6 weeks after discharge. Two years after admission, current wheeze in children aged > or =5 years was determined by questionnaire. Controls were recruited from children undergoing elective surgery (normal controls) and from those with skin prick test reactivity to foods (atopic controls). RESULTS: There was no difference in uEPX levels between normal controls (n=15) and atopic controls (n=8). uEPX levels were increased in children with acute PVW (n=84; p<0.001 v normal controls, p<0.01 v atopic controls) and fell on convalescence (n=20, 95% CI -217 to -31 microg/mmol creatinine, p<0.05). In children with acute PVW there was no association between uEPX and serum IgE levels or markers of clinical severity. Respiratory questionnaires were returned for 25/55 eligible children. There was no difference in uEPX level during acute PVW when stratified by "current wheeze" (n=18) or "no wheeze" (n=7) 2 years later. CONCLUSIONS: Systemic eosinophil activation is associated with PVW but is not associated with serum IgE, clinical severity, or persistence of wheeze into the early school age period.

Child, Preschool↗

Urinary leukotriene E4 in preschool children with acute clinical viral wheeze.

Cysteinyl leukotrienes (cystLTs) are important mediators of wheeze in atopic asthma, but the role of cystLTs in the pathogenesis of preschool viral wheeze (PVW) is unclear. Therefore, evidence for increased production of cystLTs in PVW was sought. Urinary leukotriene E4 (uLTE4) and serum total immunoglobulin (Ig)E were measured in children (1-5 yrs) with PVW during an acute attack (n=44) and in the convalescent phase (n=19), and compared with normal controls (n=15). The effect of atopic sensitisation was assessed in a separate group of atopic controls (n=6) in whom only uLTE4 was measured. The levels of uLTE4 were similar in normal and atopic controls and increased in acute PVW (median (interquartile range) 165 (101-285) versus 125 (82-163) ng x mM creatinine(-1)). Stratification by IgE showed that whereas uLTE4 was increased in 23 children with acute PVW and IgE > 95th percentile (median 211 (118-312) ng x mM creatinine(-1)), uLTE4 was not increased in the 21 children with acute PVW and IgE < or = 95th percentile. In the convalescent phase, uLTE4 fell in the subgroup with high IgE but not in the subgroup with low IgE. It is concluded that increased cysteinyl leukotriene production during acute preschool viral wheeze is associated with high serum immunoglobulin E.

Child, Preschool↗

Suppression of autologous peripheral blood mononuclear cell proliferation by alveolar macrophages from young infants.

Maintenance of lung homeostasis involves a complex interaction between T lymphocytes and alveolar macrophages (AM), in which AM suppress pulmonary T cell proliferation to antigenic stimuli. To assess whether AM-mediated suppression is attenuated in healthy young infants, AM and peripheral blood mononuclear cells (PBMC) were sampled prior to elective surgery. Children were divided into <4 months of age (Group I) and >4 months (Group II). Autologous PBMC and AM were co-cultured in vitro with phytohaemaglutinin (PHA) at AM : PBMC ratios ranging from 2:1 to 1 : 5. Methyl-tritiated thymidine was added after 48 h and uptake determined at 72 h. Percentage suppression or enhancement of PBMC proliferation by AM was determined relative to proliferation of PBMC with PHA. To determine the role of soluble factors of suppression, cell-free supernatants from paediatric AM and PBMC co-cultures were added to PHA-stimulated adult PBMC. The median age was 3 months for Group I (n = 9) and 7 years 2 months (n = 13) for Group II. Percentage suppression of PBMC proliferation was attenuated in Group I (versus Group II) at AM : PBMC ratios of 2:1 (median 78 versus 92, P< 0 x 05) and 1 : 1 (45 versus 87, P< 0 x 01). Cell-free supernatants from Groups I and II suppressed proliferation of adult PBMC, but there was no difference in suppression between the age groups. We conclude that suppression of autologous PHA-stimulated PBMC proliferation by AM is attenuated in young infants, and this immaturity is not explained by reduced release of soluble factors.

Adolescent↗

The health effects of fossil fuel derived particles.

Over the past 10 years there has been increasing evidence that particles generated by the combustion of fossil fuels adversely affect health. To what extent should paediatricians be concerned about particle pollution? This review assesses what we know, and what we still need to know about the health effects of fossil fuel particles.

Adolescent↗

Applicability of laser scanning cytometry to study paediatric alveolar macrophages.

Laser scanning cytometry (LSC) generates quantitative information on immune receptor expression from cells cytocentrifuged onto a microscope slide. In children, the description of developmental changes in immune receptor expression on alveolar macrophages (AM) has been limited by the small number of cells recovered by bronchoalveolar lavage (BAL). The applicability of LSC to the study of AM from normal children was therefore assessed. AM were obtained by BAL of normal children following intubation prior to elective surgery. The ability of LSC to identify the cytoplasm of AM was assessed using either: 1) autofluorescence; 2) forward scatter; 3) nuclear staining with propidium iodide; or 4) a fluorescent-labelled monoclonal antibody to CD68, a pan-macrophage antigen. LSC could only reliably identify individual AM when stained with CD68. The sensitivity for detecting single whole AM using CD68 was 0.97 and the positive predictive value was 0.88, respectively, with excellent repeatability. In addition, a range of immunofluorescence parameters were generated for CD68. It is concluded that laser scanning cytometry is suited to the study of immune receptor expression from small numbers of paediatric alveolar macrophages, when CD68 is used for cell identification.

Antigens, CD↗

Ultrafine particles in alveolar macrophages from normal children.

BACKGROUND: Increased ambient levels of particulate matter <10 microm (PM(10)) from fossil fuel combustion are associated with an increased prevalence of respiratory symptoms in children. However, it is unknown whether, and to what extent, pollutant particles penetrate the paediatric lower airway. The capacity of alveolar macrophages (AM) to phagocytose inhaled material was used to directly assess exposure of normal children to particles. METHODS: AM from 22 children aged 3 months to 16 years with no respiratory symptoms were obtained by non-bronchoscopic bronchoalveolar lavage prior to elective surgery. In each child the size and composition of environmental particles within single sections from 100 separate AM was determined by electron microscopy and microanalysis. RESULTS: Single and clusters of particles were seen in AM from all children. The percentage of particle-containing AM ranged from 1% to 16% per child. Particles consisted of a carbonaceous core and all were ultrafine (<0.1 microm). Other elements such as metals and silicon were not detected. The percentage of particle-containing AM did not change with age, but was increased in children whose parents lived on a main road compared with those living on a quiet residential road (median 10% v 3%, p = 0.014). CONCLUSIONS: All children had AM containing ultrafine carbonaceous particles. The predominant source of these particles is most likely to be from the combustion of fossil fuels.

Adolescent↗