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Biomedical subjects

C F Robertson

Publications and source records attributed to C F Robertson.

At least 37 records · Page 2Linked to original sources

Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins.

We measured asthma in the last 12 mo, diagnosed by a respiratory physician at interview; atopy, defined by a positive skin prick test to any of eight common allergens; and bronchial hyperresponsiveness (BHR) to hypertonic saline, in 381 twin pairs aged 8 to 18 yr selected from the Australian Twin Registry-183 monozygous (MZ) and 198 dizygous (DZ). The associations between twins, as measured by an odds ratio, were greater in MZ pairs compared with DZ pairs for asthma: 25.6 (95% confidence interval 11.3- 57.8) versus 1.9 (1.0-3. 5); atopy: 14.6 (7.1-30.1) versus 2.5 (1.4- 4.5); and BHR: 14.1 (6. 4-31.0) versus 4.2 (2.1-8.6) (all p < 0.002). The associations between each pair of traits within an individual were slightly greater than the association between one trait in a twin and the other trait in the cotwin (cross-trait cross-pair) in MZ pairs. Further, the associations in MZ pairs were greater than in DZ pairs (p < 0.05). Under the assumptions of the classic twin model, these data suggest that the strong cross-sectional associations between these three traits are due to an overlap between the genetic factors involved in each of these three traits.

Adolescent↗

Vallecular cysts in newborns and young infants.

Vallecular cyst is a rare cause of stridor and respiratory distress in infancy and has been associated with sudden airway obstruction resulting in death. In a retrospective review of eight cases over a 20-year period all infants developed symptoms during the first week of life. All had stridor and feeding difficulties and two required endotracheal intubation. Other common findings included signs of increased work of breathing and episodes of cyanosis. Failure to thrive was present in five patients diagnosed later than the first week of life. An abnormal or a hoarse cry was present in only two patients. Diagnosis in all cases was made by endoscopy. Where a VC is clinically suspected, it is important to stress the need to visualize the base of the tongue during any diagnostic endoscopic procedure. At endoscopy, a smooth localized mass arising from and distorting the lingual surface of the epiglottis was identified. Histologically, the cysts contained respiratory epithelium with mucous glands with an external lining of squamous epithelium. Treatment by cyst marsupialization is safe and definitive, in particular when performed by CO2 laser.

Airway Obstruction↗

Bronchoalveolar lavage fluid cellularity and soluble intercellular adhesion molecule-1 in children with colds.

Viral colds are an important cause of respiratory symptoms in normal children. Studies in adults suggest that inflammation in the lower respiratory tract is associated with viral colds, but there are no data regarding inflammation and viral infection in the lower airway of normal children with colds. We, therefore, studied the lower airway of two groups of children: Group I, those with active coryzal symptoms and a respiratory virus isolated from bronchoalveolar lavage fluid (BALF); and Group II: asymptomatic children who had had a clinical cold within the previous 2 weeks and no respiratory virus in BALF. Both groups were compared to age- and weight-matched normal noninfected controls, who had had no coryzal symptoms for at least 8 weeks. Viruses isolated from BALF of Group I (n = 7) were: respiratory syncytial virus (n = 2), rhinovirus (n = 3), parainfluenza I (n = 1), and echovirus 11 (n = 1). Compared to normal controls, Group I had an increased BALF lymphocyte and neutrophil differential count (P < 0.05), a concomitant depressed alveolar macrophage differential count (P < 0.05), and increased BALF concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) (P < 0.05, n = 6), total protein (P < 0.05, n = 6) and albumin (P < 0.05, n = 7). Similar changes were seen in Group II (n = 22), with an increased BALF neutrophil (P < 0.05) and lymphocyte (P < 0.01) differential count, and increased concentrations of sICAM-1 (P < 0.01, n = 15), total protein (P < 0.0001, n = 9) and albumin (P = 0.05, n = 17). Our results suggest that inflammation and viral infection in the lower airway are present during active colds, and that inflammation is also present during the convalescent period.

Adolescent↗

Soluble intercellular adhesion molecule-1 in the bronchoalveolar lavage fluid of normal children exposed to parental cigarette smoke.

This study sought to test the hypothesis that normal children exposed to parental cigarette smoke have increased bronchoalveolar lavage (BAL) fluid levels of soluble intercellular adhesion molecule (sICAM)-1. Cells and solutes from the lower airway of normal children were obtained by nonbronchoscopic BAL using three aliquots of 1 mL x kg body weight(-1) normal saline, prior to elective orthopaedic surgery. Children with evidence of recent or ongoing infection, atopic disease, previous history of wheeze, and chronic respiratory symptoms were excluded. Twelve children with parents who smoked (group 1) were paired with 12 age- and weight-matched controls with self-reported nonsmoking parents (group 2). There was no significant difference (group 1 versus 2) in the volume of BAL fluid recovered (median 29.0 versus 28.7 mL), the percentage of alveolar macrophages (92.5 versus 91.8%), neutrophils (1.1 versus 2.1%), lymphocytes (5.3 versus 5.6%) and eosinophils (0 versus 0%), and the total BAL fluid leukocyte concentration (80 versus 61 x 10(3) cells x mL(-1)). BAL fluid albumin concentration was similar between the two groups (0.033 versus 0.020 mg x mL(-1)). sICAM-1 was detected in all BAL fluid samples, and was significantly increased in group 1 (39.2 versus 22.5 ng x mL(-1), p<0.01). It was concluded that exposure of children to parental cigarette smoke is associated with increased soluble intercellular adhesion molecule-1 concentrations in the bronchoalveolar lavage fluid and this may reflect an altered activation of pulmonary immune cells.

Adolescent↗

Early use of inhaled nedocromil sodium in children following an acute episode of asthma.

BACKGROUND: Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma. METHODS: A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment). RESULTS: One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group. CONCLUSIONS: Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber.

Acute Disease↗

Alveolar macrophage immaturity in infants and young children.

Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (<2 yrs), group 2 (> or =2-< or =5 yrs) and group 3 (> or =6-< or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: <2 yrs and > or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children <2 yrs expressed less human leukocyte antigen (HLA)-DR (versus > or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children <2 yrs and > or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.

Adolescent↗

Asthma and other atopic diseases in Australian children. Australian arm of the International Study of Asthma and Allergy in Childhood.

OBJECTIVE: To determine the prevalence of asthma, eczema and allergic rhinitis in Australian schoolchildren using the protocol of the International Study of Asthma and Allergy in Childhood (ISAAC). DESIGN: Questionnaire-based survey. SETTING: Melbourne, Sydney, Adelaide (in winter-spring, 1993) and Perth (in winter-spring, 1994). SUBJECTS: All children in school years 1 and 2 (ages 6-7 years) or in year 8 (ages 13-14 years), attending a random sample of 272 schools, stratified by age and city. MAIN OUTCOME MEASURES: Parent-reported (for 6-7 year olds) or self-reported (for 13-14 year olds) symptoms of atopic disease in the previous 12 months, or ever; treatment of asthma; and country of birth. RESULTS: 10,914 questionnaires were completed for 6-7 year olds and 12,280 for 13-14 year olds (84% and 94% response rates, respectively). Prevalence of wheeze in the past 12 months was 24.6% for the 6-7 year olds and 29.4% for the 13-14 year olds, and, among 6-7 year olds, was significantly higher in boys (27.4%) than girls (21.7%). Children born in Australia were more likely to report current wheeze than those born elsewhere (6-7 year olds: odds ratio [OR], 1.82; 95% confidence interval [CI] 1.55-2.15; and 13-14 year olds: OR, 1.88; 95% CI, 1.68-2.11). Prevalences of current eczema and allergic rhinitis were 10.9% and 12.0%, respectively, for the 6-7 year olds, and 9.7% and 19.6%, respectively, for the 13-14 year olds. Asthma, eczema and rhinitis coexisted in 1.8% of 6-7 year olds and 2.8% of 13-14 year olds. CONCLUSION: This study provides evidence that asthma prevalence in Australian schoolchildren is continuing to increase and is higher among Australian-born children than among those born elsewhere. Asthma, eczema and allergic rhinitis coexist to a lesser extent than expected. These results form the basis for future Australian and international comparisons.

Adolescent↗

Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.

OBJECTIVE: To compare the efficacy of salbutamol delivered by jet nebuliser (JN) with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume spacer (Volumatic) for management of acute asthma. STUDY POPULATION: A total of 160 children aged from 4 to 12 years presenting to an Emergency Department with acute asthma. METHODS: The study was of multicentre (n=5) randomised, double blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5 mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI. Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and 15, 30, 45 and 60 mins post administration. RESULTS: The improvement from baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI (P=0.001). CONCLUSION: Administration of salbutamol via a PMDI and a large volume spacer device provides effective relief in the management of acute asthma in children, but to a lesser extent than a jet nebuliser. This difference may represent a dose response effect.

Acute Disease↗

Multiple leiomyosarcomas of both donor and recipient origin arising in a heart-lung transplant patient.

The occurrence of Epstein-Barr virus-associated smooth-muscle tumors in immunocompromised patients has been reported, particularly in the pediatric population. In posttransplantation tumors, the tissue of origin has been either donor or recipient. Mixed-genotype sarcomas within the same patient have not yet been reported. We describe the occurrence of multiple leiomyosarcomas of both donor (arising in the lung allograft) and recipient (arising in the host liver) origin in a 15-year-old boy 3 years after heart-lung transplantation. Analysis of premortem lung tumors demonstrated the presence of Epstein-Barr virus DNA. Despite decreasing immunosuppression and commencing acyclovir, the patient died of systemic Pseudomonas infection. Immunohistochemical analysis revealed that both lung and liver tumors were negative for the Epstein-Barr virus receptor (CD21), and suggests that Epstein-Barr virus entry into the cells was not via this receptor but via an alternate mechanism such as cell fusion.

Adolescent↗

Preventable factors in hospital admissions for asthma.

Asthma remains the second most common cause for admissions to a paediatric hospital bed. The aim of this study was to describe the characteristics of children admitted to hospital with an acute asthma attack and to identify factors that may prevent future hospital admissions. Parents of all children aged 3 to 15 years admitted to hospital for acute asthma were interviewed and the child's case record reviewed. Children were recruited consecutively in two groups: 141 summer/autumn and 125 winter/spring 1996. According to the pattern of symptoms in the previous 12 months, 61% of the children had infrequent episodic asthma, 26% had frequent episodic asthma, and 13% persistent asthma. Only 8% of children aged 8 years or less had persistent asthma, in contrast to 22% of those aged > 8 years. There was evidence of both inadequate prescription of preventive treatment and poor compliance in the frequent episodic and persistent asthma groups. Of the whole group, 44% had previously been given an acute asthma management plan, but only 9% of them used it before the current hospital admission. There was a delay in seeking medical advice (> 24 hours after the onset of symptoms) in 27% of all admissions. This study has identified potential areas where intervention may reduce the number of future admissions.

Acute Disease↗

A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough.

AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response. DESIGN: Randomised, double blind, placebo controlled trial. METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests. RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR. CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.

Administration, Inhalation↗

Totally implantable venous access devices in children with cystic fibrosis: incidence and type of complications.

BACKGROUND: Totally implantable vascular access devices (TIVADs) are accepted as a safe and effective method of facilitating long term intravenous therapy. We report our experience of the use of these devices in children with cystic fibrosis with a particular focus on the incidence and type of complications. METHODS: The medical records of patients with cystic fibrosis who underwent placement of a TIVAD at the Royal Children's Hospital, Melbourne, Australia from January 1987 to October 1996 were reviewed. Venous ultrasonography with Doppler was performed in surviving patients with a TIVAD in situ from November 1996 to April 1997 to detect occult thrombotic complications. RESULTS: A total of 57 TIVADs were implanted in 44 children with a median functional duration of 700 days (range 27-3347 days). Twenty one children had devices inserted without complications. Forty eight complications (30 mechanical, 18 infectious) occurred in 36 devices in 23 children during a total functional duration of 53,057 catheter days. Mechanical complications occurred in 53% of devices (one per 1712 catheter days). Symptomatic venous thrombosis occurred five times in four patients (9%). Infectious complications occurred in 32% (one per 2948 catheter days) while sepsis occurred in five devices (9%). Doppler ultrasonography detected unsuspected thrombosis in two of 10 patients examined. CONCLUSIONS: While TIVADs provided effective long term intravenous access, septic and thrombotic complications caused significant morbidity in this population. Careful patient selection, adherence to aseptic technique for access and blood sampling, and periodic ultrasonography with Doppler to detect early thrombosis may help reduce these risks.

Adolescent↗

Subjective scoring of cough in children: parent-completed vs child-completed diary cards vs an objective method.

Cough is often used as an outcome measure, although the reporting of cough is unreliable. Using a 24 h ambulatory cough meter to measure cough frequency, the aim of this study was to compare: 1) the correlation of child-completed diary cards to the objective measurement, with that of parent-completed diary cards; and 2) the visual analogue scale (VAS) to the verbal category descriptive (VCD) score. The cough meter consisted of a previously validated Holter monitor and a cough processor. Eighty four children (39 with recurrent cough and 45 controls, aged 6-17 yrs) used a cough meter at least once. Thirty three subjects used the cough meter twice. Parents and children completed separate diary cards using the VAS and VCD scores. The strength of the relationship between the subjective scores and the objective recordings was analysed by spearman's rank correlation coefficient. For daytime cough, child-completed diary cards and the VCD correlated better to the objective measurement than parent-completed diary cards and the VAS, respectively. In subjects that used the cough meter twice, the difference between the cough frequency correlated to the difference in the subjective scores. The confidence intervals for the correlation coefficients were wide. The agreement between the objective and subjective presence of daytime cough was good but that for night-time cough was poor. We conclude that the severity of cough defined on diary cards may not represent cough frequency. Objective readings are first choice but currently not yet practical. The verbal category descriptive diary card completed by children and assisted by parents has the highest correlation to cough frequency measured objectively.

Adolescent↗

Effect of capsaicin on airway responsiveness to hypertonic saline challenge in asthmatic and non-asthmatic children.

Recurrent cough and asthma are common problems in children. In the evaluation of children with recurrent cough, the sequential measurements of airway responsiveness (AR) and capsaicin cough receptor sensitivity may be useful. However, the effect of capsaicin on AR induced by an indirect stimulus such as hypertonic saline (HS) is not known. Current evidence suggests that a common pathway is involved in both capsaicin and HS challenges. This study was designed to determine whether inhalation of capsaicin for the cough receptor sensitivity test before HS challenge will alter AR of asthmatic and non-asthmatic children to that challenge. Twenty-one children (12 asthmatics, 9 non-asthmatics; mean age, 11.3 years) performed the HS challenge alone or 2 min after capsaicin inhalation on 2 different days in random order. The end point of the capsaicin inhalation was when > or = 5 coughs were stimulated from a single inhalation. The power of the study was > 90% at a significance level of 0.05. Capsaicin inhalation prior to HS challenge did not alter the AR of normal children. In the asthmatic group, the PD15 (provocation dose causing a fall in forced expiratory volume in 1 s of > or = 15% from the baseline) without prior inhalation of capsaicin (mean, 2.44 +/- SEM 1.21 ml) was not significantly different from that when HS challenge was performed after capsaicin inhalation (mean, 2.19 +/- SEM 0.83 ml). The mean of the difference in log PD15 of the HS challenge with and without capsaicin was -0.02 (95% CI, -0.16, 0.12), i.e. within the equivalence range of the HS challenge in children with asthma. We conclude that in normal and asthmatic children, capsaicin inhalation does not alter AR to HS; consequently the capsaicin cough sensitivity test can be performed validly before an HS challenge.

Adolescent↗

Pulmonary diseases in children with severe combined immune deficiency and DiGeorge syndrome.

Pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. We retrospectively reviewed 15 children with severe combined immune deficiency (SCID) and 19 children with DiGeorge syndrome at the time of their first presentation to the Royal Children's Hospital in the 15-year period from 1981 to 1995. In children with SCID, pulmonary disease was a common (67%) presenting feature and the organisms identified were Pneumocystis carinii (PCP) (n = 7), bacteria (n = 4), viruses (n = 3), and a fungus (n = 1). Late pulmonary complications included lower respiratory tract infections, bronchiolitis obliterans, and lymphointerstitial pneumonitis. Pulmonary infections were common (17 occasions) and the organisms identified were bacteria (n = 7), viruses (n = 6), fungi (n = 3), and Mycobacterium tuberculosis (n = 1). Pulmonary complications were responsible for 5 of 9 deaths. PCP was not identified as a late complication in any child, presumably as a result of effective prophylactic therapy. Although pulmonary disease was not a major presenting feature in children with DiGeorge syndrome, pulmonary complications were common. These included recurrent bacterial and viral infections and bronchomalacia, which complicated management and predisposed to morbidity and mortality, even in those without a T-cell defect. We conclude that pulmonary disease is a common manifestation in children with SCID and DiGeorge syndrome.

CD4 Lymphocyte Count↗

Subglottic haemangioma.

OBJECTIVES: To describe experience with subglottic haemangioma in a unit where conservative treatment has been favoured. METHODS: Retrospective case note review of infants presenting with subglottic haemangioma over a 25 year period. RESULTS: Thirty one infants were identified. Diagnosis was difficult where skin haemangiomas were absent and where the lesion was circumferential rather than asymmetrical. Tracheostomy was safe, well tolerated, and managed by the patients' family at home. Major complications were seen only when laser treatment was used. CONCLUSIONS: Aggressive treatment with substantial risks of long term complications may not be necessary in this spontaneously resolving disorder.

Female↗

Cough sensitivity in children with asthma, recurrent cough, and cystic fibrosis.

In adults, cough sensitivity is influenced by gender and is heightened in those with non-productive cough. This study examined if cough sensitivity is (i) altered in children with asthma, recurrent cough, and cystic fibrosis and (ii) influenced by age, gender, or forced expiratory volume in one second (FEV1). Cough sensitivity to capsaicin and spirometry were performed on 209 children grouped by the diagnosis of asthma, recurrent dry cough, cystic fibrosis, and controls. Cough sensitivity was increased in children with recurrent cough, and lower in children with cystic fibrosis when compared with children with asthma and controls. Age influenced cough sensitivity in the controls. In the asthmatics, FEV1 (% predicted) correlated to cough sensitivity measures. There was no gender difference in cough sensitivity. It is concluded that cough sensitivity is different among children with recurrent dry cough, asthma, and cystic fibrosis. In children, age, but not gender, influences cough sensitivity measures and when cough sensitivity is used in comparative studies, children should be matched for age and FEV1.

Adolescent↗