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Biomedical subjects

J F Price

Publications and source records attributed to J F Price.

At least 19 recordsLinked to original sources

Sputum cysteinyl-leukotriene levels correlate with the severity of pulmonary disease in children with cystic fibrosis.

Sputum samples from 13 children with cystic fibrosis (CF) were analyzed for leukotrienes (LTs) LTB4, LTC4, LTD4, and LTE4. Distribution of LTB4 appeared to be normal, and of cysteinyl-LTs log normal. Total cysteinyl-LT levels, of which on average 75% was LTE4, were nearly 10 times higher than in earlier studies. Log LTE4 and total cysteinyl-LT levels correlated with the overall severity of pulmonary disease assessed by Chrispin-Norman chest radiograph score (Log LTE4: r = 0.701, r2 = 49.1%, P = 0.008. Log total cysteinyl-LTs: r = 0.715, r2 = 51.1%, P = 0.006). There was no apparent relationship between LTB4 levels and Chrispin-Norman chest radiograph score, nor between the level of any of the LTs and age or organism cultured from sputum. These findings suggest that the cysteinyl-LTs may be involved in the pathophysiology of pulmonary disease in CF.

Child

The IgG subclass antibody response to an inhalant antigen (Dermatophagoides pteronyssinus) during the first year of life: evidence for early stimulation of the immune system following natural exposure.

This study investigates the early humoral immune response following natural exposure to an inhalant antigen (Dermatophagoides pteronyssinus) in 36 babies, from birth until 1 year of age. The total IgG and subclass 1 and 4 D. pteronyssinus-specific antibody levels were assayed in sera collected at 7 days, 3 and 12 months by ELISA. After an initial fall, due to the progressive loss of maternal antibodies, an IgG specific response to D. pteronyssinus was seen between 3 and 12 months. This was restricted to the IgG1 subclass when the values at 12 months were significantly higher than those detected at the third month (P less than 0.001, paired t test). No D. pteronyssinus-specific IgG4 antibody was detected in any subject at any of the time points tested. The present study demonstrates that inhalant as well as food antigens are able to stimulate the immune system during the first year of life and that the antibodies produced are of the IgG1 subclass.

Administration, Inhalation

Higher risk of infantile atopic dermatitis from maternal atopy than from paternal atopy.

The risk of infantile atopic dermatitis (AD) posed by maternal atopy and paternal atopy, respectively, were compared in the infants from a birth cohort in whom one of the parents had been designated atopic by skin prick testing. Nineteen with atopic mothers were compared with 20 with atopic fathers. AD, other atopic manifestations and potentially influential factors such as breast-feeding were documented prospectively during the first year in all infants. At 3, 6 and 12 month assessments skin prick sensitivity and total serum IgE concentration were determined. Nine of 19 infants with atopic mothers and two of 20 with atopic fathers had AD (P = 0.023) giving a relative risk of 4.7 (95% confidence interval 2.5 to 9.0). Seven of 19 with atopic mothers and none with atopic fathers had AD with onset before 6 months (P = 0.007). When all types of disease evidence (AD, recurrent wheeze and food reactions) were analysed together no significant difference was apparent between the groups. The two groups were found to be well matched with regard to breast-feeding, time of starting cow's milk, solids and egg, sex, month of birth, parental AD and smoking, race, household pets and neonatal IgE concentration. IgE concentrations at each age and the prevalence of skin prick positivity were similar between the groups. Maternal atopy poses a higher risk for infantile AD and paternal atopy. Whether this may be due to genetic or congenital factors or both is uncertain, but clearly the finding is of relevance in the prediction of allergy in childhood.

Adult

Prevention of exercise induced asthma by inhaled salmeterol xinafoate.

The effect of inhaled salmeterol xinafoate, a long acting beta 2 agonist, on exercise induced asthma was studied in a double blind, crossover, and placebo controlled trial. Thirteen asthmatic children with a fall of at least 15% in their forced expiratory volume in one second (FEV1) after a standard exercise test on a motorised treadmill, on separate days performed the same test 1, 5, and 9 hours after a single dose of 50 micrograms salmeterol or placebo. FEV1 was measured before treatment, and before and for 30 minutes after each exercise test. After placebo the number of children with exercise induced asthma was: 10 at 1 hour, 11 at 5 hours, and 12 at 9 hours. Salmeterol prevented exercise induced asthma in all 13 children studied, at 1, 5, and 9 hours. Mean maximum falls in FEV1 after exercise were at 1 hour: salmeterol 2.7% and placebo 24.6%, 5 hours: salmeterol 5.3% and placebo 22.7%; and 9 hours: salmeterol 3.4% and placebo 26.6%. After salmeterol the mean increase in FEV1 was 17.8% at 1 hour, 19.6% at 5 hours, and 19.2% at 9 hours. Inhaled salmeterol prevents exercise induced asthma and produces significant bronchodilatation for at least 9 hours.

Administration, Inhalation

Early immune responses to Dermatophagoides pteronyssinus and atopic predisposition.

Responses to the house dust mite during infancy may be important determinants of asthma in susceptible individuals. This study assessed early IgG subclass antibody responses to Dermatophagoides pteronyssinus in children of atopic parents. Sixteen atopic and 15 non-atopic children were selected from a birth cohort, and atopic status was established according to follow up over the first two years. IgG1 and IgG4 antibodies to D pteronyssinus were measured by enzyme linked immunosorbent assay at 7 days and 3, 6, 12, and 24 months. In all children D pteronyssinus IgG1 fell at 3 months (indicating maternal antibody loss), rose progressively to 12 months, and waned at 24 months. D pteronyssinus IgG4 was only detectable at 7 days. Children who were atopic by 2 years and therefore at greater risk of asthma, tended to have higher D pteronyssinus IgG1 at 6 and 12 months. These data suggest greater exposure or responsiveness to dust mite during infancy than in the second year.

Aging

The effect of postexsanguination infusion of beef on composition, tenderness, and functional properties.

Ninety culled dairy cows were used in this study and were paired by weight and conformation similarity. Forty-five cows were arterially infused immediately after bleeding with 10% volume by weight of a solution composed of dextrose (.23%), glycerin (.21%), a phosphate blend (.14%) and maltose (.1%). The remaining cows (45) served as controls. In infused carcasses, some quantity of solution retained was in the following order: supraspinatus, chuck greater than longissimus, loin greater than semitendinosus, round muscles. Accordingly, percentage of protein, ether-extractable fat, and protein fat-free amounts were lowered (P less than .05) and percentage of moisture and moisture protein ratio were raised (P less than .05) in the supraspinatus muscle. Tenderness (P less than .01) and protein extractability (P less than .15) were improved. No difference was observed in water-holding capacity between infused and control carcasses. Percentages of moisture fat-free (r = .85) and protein fat-free (r = -.97) were highly correlated to moisture-protein ratio. Moisture percentage of the fat-free tissue was shown to be a more consistent indicator of added moisture in infused whole carcasses compared with moisture:protein ratio and percentage of protein fat-free. Very low correlations were observed between tenderness, percentage of moisture, percentage of water-holding capacity, and ether-extractable fat. The economics of the infusion process to the beef industry is discussed.

Animals

Importance of using lung function regression equations appropriate for ethnic origin.

Functional residual capacity (FRC) can be assessed reliably in young children using a helium gas dilution technique. The aim of the present study was to determine if differences in lung volume are found in asthmatic children of different ethnic origins. Eighty-eight children were studied, 53 of Caucasian origin and 35 of Afro-Caribbean origin. Their median age was 6.1 years (range, 5.3-9.0 years). FRC measured by helium gas dilution is reported as a percentage of predicted for height, using a published regression equation as well as regression equations appropriate for the ethnic origin of the child. In the majority of both groups FRC was elevated above the ethnically appropriate regression equation for healthy children. The Caucasian children apparently had higher FRCs than the Afro-Caribbean children if comparing the absolute lung volume, and if lung volume was expressed as percent of predicted for height, by a regression equation uncorrected for ethnic origin (P less than 0.02). This difference disappeared when ethnically appropriate regression equations were used. We conclude that lung volumes are similar in asthmatic children of different ethnic origin and that it is important to use ethnically appropriate regression equations.

Asthma

The IgE and IgG subclass antibody response to foods in babies during the first year of life and their relationship to feeding regimen and the development of food allergy.

This follow-up study of 191 babies investigated the development of food allergy in an unselected population and its relationship to total and antigen-specific IgE and IgG subclass levels. Sensitization to egg, as indicated by a positive skin test or RAST, was found in 5% of 1-year-old babies, but none of the babies in this series fulfilled the clinical criteria for immediate-type milk allergy. For both bovine casein (CAS) and egg albumin, the IgG response was largely restricted to IgG1 in contrast to the predominant IgG4 response to these antigens that is found in adults. The level of IgG4, but not IgG1, antibody to CAS and ovalbumin (OV) was lower in some of the babies compared with that of their mothers (N = 166; p less than 0.05, Student's paired t test). However, there was no difference in the total serum IgG subclass levels between mothers and babies. These results demonstrate that, in the population of babies studied, (1) type I hypersensitivity to egg occurred in 5% of 1-year-old babies, (2) the predominant IgG subclass of antibodies to CAS and OV in babies is IgG1, and (3) in the 22% of babies, there was substantially (greater than 1000-fold) less IgG4 antibody to CAS and OV than in their mothers, suggesting specific exclusion of some IgG4 antibodies.

Antibody Specificity

A 2-year longitudinal study of lung hyperinflation in young asthmatics.

Functional residual capacity (FRC) was measured at 6-monthly intervals for at least 2 years in 42 young asthmatic children. Over the 2-year period FRC decreased in the 42 children from a median of 136% to 117% of that predicted for height (P less than 0.05). These changes in FRC were associated with a reduction in the number of children receiving no regular treatment (ten at recruitment, 0 at 2 years), P less than 0.05, and an increase in the number of children receiving inhaled steroids (ten at recruitment and 29 at 2 years), P less than 0.01. Twenty-five children were hyperinflated at recruitment (FRC greater than 120% of that predicted for height) with median FRC 152% compared to only 16 children at 2 years median FRC 117%, P less than 0.01. We conclude that FRC decreases as asthmatic children get older but some children, worryingly and despite increased use of prophylactic therapy, remain chronically overdistended which may put them at serious risk of chronic obstructive airways disease in later life.

Anti-Inflammatory Agents

Neonatal IgE: a poor screen for atopic disease.

Screening for atopic disease using neonatal serum IgE has been advocated on the basis of the predictive value of elevated levels. However, this is only one measure of validity. The test was validated fully in 92 infants with a bi-parental history of atopy using 0.7 IU/ml as the cut-off. All infants were assessed prospectively for evidence of atopic disease (eczema, recurrent wheezing or food reactions) and skin-prick test positivity in the first year. Total serum IgE was measured by ultrasensitive ELISA on 61 cord blood samples and 92 samples taken at 7 days. All cord samples were re-analysed by PRIST and the first 33 by ultrasensitive RIA giving, respectively, 82% and 94% concordance (regarding undetectable, detectable and elevated levels) with ELISA. Maternal contamination was indicated in 7% of cord samples by high serum IgA. Ninety-five per cent of cord/7-day IgE pairs showed no change or minor rises at 7 days. Forty-nine per cent of the infants had evidence of atopic disease. Only 5% had elevated 7-day IgE. The positive and negative predictive values of the 7-day test were 60% and 52%, respectively, and specificity 96% but the sensitivity was only 7%. High levels did not distinguish the infants with the most unequivocal evidence of disease, i.e. eczema with a positive skin test. In conclusion IgE at 7 days is comparable to and more reliable than cord IgE. However, neonatal IgE screening is too insensitive to have clinical application.

Enzyme-Linked Immunosorbent Assay

Relation between nocturnal symptoms and changes in lung function on lying down in asthmatic children.

Nocturnal symptoms are common in young asthmatic children. Such symptoms may be caused by increased impairment of lung function when they adopt the supine posture. Thirty one children aged 2.8-8.3 years were studied, of whom 20 had asthma (10 with frequent nocturnal symptoms) and 11 had no respiratory problems (control subjects). Peak expiratory flow (PEF) was measured with a Wright's peak flow meter and functional residual capacity (FRC) by a helium gas dilution technique after 30 minutes of lying supine; the values were compared with FRC measured sitting and PEF standing. Peak flow fell significantly on adoption of the supine posture in the asthmatic children, but there was no difference in this fall between the asthmatic children with and without nocturnal symptoms. FRC also fell on adoption of the supine posture, but the decrease in FRC was significant only in the control children and the asthmatic children without nocturnal symptoms. The failure to find a greater fall in PEF or a greater change in FRC on adoption of the supine posture among asthmatic children with nocturnal symptoms suggests that mechanisms other than increased impairment of lung function are responsible for nocturnal asthma.

Asthma

Acute and long-term effects of viral bronchiolitis in infancy.

About 1% of infants are admitted to hospital with acute bronchiolitis; 85% of cases are caused by infection with Respiratory Syncytial Virus (RSV). The pathophysiological changes during the acute illness are inflammatory obstruction in the small airways with submucosal cellular infiltration, epithelial necrosis and mucous plugging; FRC increases and dynamic compliance falls. Failure to respond to bronchodilator drugs suggests that muscle spasm contributes relatively little to the airway narrowing. Affected infants become increasingly dyspnoeic and hypoxic for 3-4 days then spontaneously improve. After an attack of acute bronchiolitis up to 75% of children have recurrent lower respiratory tract symptoms, many continue to have hyperinflated lungs and bronchial hyperresponsiveness. In the majority, symptoms of cough and wheezing have subsided by the time they start school, but abnormalities of small airway function are detectable at least 13 years later. Children with a genetic predisposition to atopy do not appear to have an increased risk of developing bronchiolitis. Evidence of genetic predisposition to bronchial hyperresponsiveness in those with persistent wheezing is controversial. There is little to suggest that neonatal lung damage or an adverse home environment are important factors in determining susceptibility to post-bronchiolitis wheezing. IgE antibodies to RSV, and leukotriene C4, are found more frequently in the respiratory secretions of infants who wheeze during and after bronchiolitis than in those who do not. The possibility of viral-induced alteration of the immune response at the time of infection needs further investigation.

Bronchial Provocation Tests