Biomedical subjects
Publications and source records attributed to F Carswell.
Air samples taken from the clean air over Bristol were examined using scanning, transmission and X-ray probe micro-analysis. A diversity of material was identified demonstrating the importance of man-made pollutants which have the potential to produce lung damage in addition to pollen moulds.
The sites and concentrations of Der p I within the house dust mite were determined. Highest concentrations were found in the epithelium of the posterior end of the mite stomach, implying that this is the site of Der p I synthesis and secretion.
Forty-seven patients with cystic fibrosis (CF) studied in 1977 have been followed up and reviewed, with respect to the development of immediate cutaneous hypersensitivity to Aspergillus fumigatus and other allergens, and the date of Pseudomonas aeruginosa colonization. The prevalence of cutaneous hypersensitivity to inhaled allergens in CF increases with longer allergen exposure, to the extent that the CF patients develop a prevalence of atopy greater than normal controls. Allergen-sensitive patients were found to develop Pseudomonas colonization later, but to have a shorter survival subsequently; there was no relationship between skin tests and overall survival.
Uncontrolled studies of avoidance of house dust mite (Dermatophagoides pteronyssinus) by atopic subjects have reported clinical improvement in the severity of eczema. The aim of the present study was to examine the temporal relationship between environmental exposure to the major mite allergen (Der pI) and clinical disease severity in children with chronic atopic eczema. Twelve children were identified as being house dust mite-sensitive on the basis of skin prick test and RAST to Der pI. They were examined on two occasions with a median interval of 63 days. Clinical severity of eczema improved in nine children and deteriorated in two children during this period. Der pI concentration in dust from mattresses changed significantly in only three subjects and there was no correlation between changes in clinical severity and changes in environmental Der pI exposure. Change in RAST against Der pI did correlate positively with change in Der pI exposure (rho = 0.56, P less than 0.05) but these changes were not associated significantly with changes in eczema severity or skin test response to Der pI. It is concluded that the observed changes in clinical severity were unlikely to be due to immediate hypersensitivity responses to natural variations in Der pI concentrations in the personal environments of these subjects.
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Seventy four asthmatic children aged 7 to 11 years were examined along with controls matched by age and sex. Clinical and laboratory investigations preceded a 28-day follow-up where data about morning and evening peak expiratory flow rate (PEF), symptoms and treatment were recorded. The coefficient of variation of PEF was found to be an objective measurement of asthma severity that has statistically significant correlation with both symptoms (rs = .36) and treatment (rs = .60). Moreover, it separates mild and severe asthmatics, as confirmed by statistically significant differences (p = .008 or less) in symptoms, treatment, skin allergy and airways response to exercise. Skin allergy and airways responsiveness to exercise were found to be predictors of both disease and severity. By means of logistic regression analysis it was possible to establish the probabilities for both asthma and severe asthma when children presenting and not presenting these characteristics are compared. One single positive skin test represent a probability of 88% for the development of asthma and a probability of 70% for severe disease. A PEF reduction of 10% after an exercise test implies a probability of 73% for disease and a probability of 64% for severe disease. Increases in these variables imply geometrically increased risks and their presence together have a multiplicative effect in the final risk.
Eighty-six families, each with an asthmatic child, were studied in their normal environment. The relationships between the physical severity of asthma and the families' knowledge and feelings about the asthma were measured. The mean peak expiratory flow rate recorded prospectively for one week correlated (R = 0.33) with the symptom score. In the 73 families who knew their child had asthma, there was a significant relationship (R = +0.28) between the knowledge of physical signs of attack severity and knowledge of the drugs available for emergency therapy. The mean peak expiratory flow rate was inversely related to the practical effectiveness of the inhaler technique (R = 0.62) only when the 12 families in whom the child's mean peak expiratory flow rate was less than 90 per cent of predicted were examined. The parents' feelings of worry and fear, measured independently, related to the family's knowledge of physical indications of the severity of asthma attacks. Although the families' overall knowledge scores were poor, they were apparently adjusting appropriately to asthma as a psychological stress as it appeared that they sought more information if they were worried. Their comprehension should improve if such knowledge was correctly delivered. There is a need to explore more effective techniques for the education of such families.
A study was undertaken to examine the circadian rhythm of peak flow rate in asthmatic and normal children in the community by means of cosinor analysis. An initial study of 12 matched pairs of asthmatic and normal children was used to determine the mean amplitude of peak expiratory flow (PEF) variability in the two groups (7.8% and 4.4%) and the number of subjects required to show a significant difference. On the basis of this study 37 community based children with asthma diagnosed by questionnaire and 40 control subjects measured PEF four times daily for 14 days. Cosinor analysis of the data produced a significant fit in 20 asthmatic and 18 control children. A small but significant difference in amplitude was observed between the asthmatic (6.2%) and the control (4.2%) children. There was no significant phase difference between the rhythms in the two groups. Cosinor analysis explained 14% of PEF variance. It did not provide a reproducible estimate of phase between week 1 and week 2; the acrophase changed by more than one hour in 26 of 37 asthmatic children. The cosinor model may be inappropriate for the investigation of low amplitude circadian rhythms, especially when measurements are made infrequently.
The care of asthmatic children is commonly sub-optimal. Accordingly the costs and benefits of sending a district health authority community nurse, who had specific training in asthma management, into the homes of 43 families with asthmatic children were assessed. During the six months the asthma nurse visited these homes, the children developed and sustained, higher peak expiratory flow rates than 43 control asthmatics. The direct costs of the asthma nurse was 15 pounds/patient/six months.
In the 11 years 1977 to 1987, 36 confirmed cases of tracheobronchial foreign body were seen in the Bristol Children's Hospital. The distribution of ages, sites, and natures of the objects inhaled are similar to those in other reviews. Complications of removal of the foreign body once diagnosed were few, and have been absent since the Storz rod lens system was introduced in 1982. Eleven patients experienced delay of at least 7 days between the beginning of the symptoms and diagnosis, of whom 3 subsequently required open thoracotomy. Six of these had sought medical advice during this period, of whom 4 had a positive history of choking or inhalation. Inhaled foreign bodies remain a source of diagnostic difficulty, although this should be improved by greater attention to history and appropriate investigation. Technical advances have ensured their safe bronchoscopic removal in most cases.
A rat model of immediate pulmonary hypersensitivity was used to investigate the permeability changes in the tracheal epithelium produced by aerosol challenge with antigen. The rats were sensitised by the intraperitoneal injection of antigen (dinitrophenyl (DNP19) ovalbumin). Sensitised and control animals were then challenged for 60 minutes with an aerosol of the same antigen, which also contained the electron dense pore marker lanthanum. Histological examination and x ray probe microanalysis showed a greater intercellular concentration of lanthanum in the tracheal epithelium in sensitised than in control animals. The results show that in sensitised rats increased intercellular penetrance of antigen can occur after antigen challenge.
The natural production of Der pl, the major faecal allergen from the house dust mite (Dermatophagoides pteronyssinus), was investigated. Mite cultures grown on radiolabelled substrate were examined at intervals over a period of 21 days and incorporation of radiolabel into the mite proteins measured over the time course. Mite proteins were extracted, purified by chromatofocussing and characterized by immunodiffusion, SDS-PAGE, electroblotting and autoradiography. The faecal allergen, Der pl, did not incorporate a significant level of label until the 14th day (p less than 0.05). The results suggest that Der pl is a protein synthesized and excreted by the house dust mite.
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An aqueous house dust mite extract was separated by SDS-PAGE and transferred to nitrocellulose membranes by Western Blotting. Two major allergens, Der pI and Der pII associated with the mite faeces and body, respectively, were identified on the protein blot. The blot was then probed with atopic sera and the bound antibodies were labelled with 125I anti-IgE and visualized by autoradiography. Using this technique it is shown that serum samples from eczema patients contain a higher proportion of anti-mite body IgE antibodies, whereas those from asthma patients contain a higher proportion of antibodies against the major mite faecal allergen Der pI. Minor mite body allergens are also shown to be important in eczematous patients. The role of mite allergens in atopic conditions is discussed, along with the significance of the findings presented here.
Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract, completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo. The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo.
The concentrations of serum IgE with specificity for the faecal and body allergens of the house dust mite, Dermatophagoides pteronyssinus, were compared in 69 children with various combinations of asthma, eczema and/or rhinitis. The concentration of IgE antibodies to the mite body was higher in those with eczema than those with asthma but the concentrations of anti-faecal antibodies were similar. Our results suggest that anti-mite body antibodies are characteristic of eczema and that sensitization to the body allergen may occur because of its passage through the skin.
Inbred rats were sensitized by intraperitoneal injection of DNP19 ovalbumin (DNP-OA) or saline. The rats were subsequently challenged by exposure to an aerosol of DNP-OA or bovine gamma globulins (BGG) for 10 min. Tracheal tissue was processed immediately after challenge in fixative containing 1% lanthanum. Planimetry of transmission electron micrographs showed 59% of the intraepithelial membranes were stained with lanthanum in the DNP-OA-sensitized and DNP-OA-challenged group; 39% in the saline-sensitized, DNP-OA-challenged group, and 26% in the DNP-OA-sensitized, BGG-challenged group. X-ray static probe microanalysis confirmed that most lanthanum penetrated in the DNP-OA-sensitized and DNP-OA-challenged group. In this group, the magnitude of the mechanical response, measured by body plethysmography, correlated directly (r = 0.74) with the lanthanum penetration. Our results confirm that increased permeability of the intercellular spaces occurs in immediate pulmonary hypersensitivity. They suggest that this change in permeability may be involved in producing the mechanical response.