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Biomedical subjects

A Bush

Publications and source records attributed to A Bush.

At least 55 records · Page 3Linked to original sources

Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial.

BACKGROUND: The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial. METHODS: 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat. FINDINGS: Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects. INTERPRETATION: A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.

Adolescent↗

Inflammatory endobronchial polyps in childhood: clinical spectrum and possible link to mechanical ventilation.

Inflammatory polyps of the airways are now regarded as histopathologically distinct nonneoplastic endobronchial lesions, which in adults are associated with a variety of chronic inflammatory insults. However, their clinical presentation in the pediatric population is extremely rare, with the etiology of such polyps poorly defined. The clinical and histopathological data from four pediatric patients, identified in the histopathology files of the Royal Brompton Hospital, were retrospectively reviewed. Three out of 4 patients had a history of mechanical ventilation in the neonatal period. In these 3 patients, the polyps were all situated in the proximal airways on the right side. These 3 patients presented at 6 weeks, 7 weeks, and 2 years, respectively, and were successfully treated by polypectomy at rigid bronchoscopy, with subsequent return to normality. One patient, presenting at 12 years of age without history of iatrogenic intervention, underwent a left lower lobectomy for a polyp sited in a segmental bronchus. Presentation in 3 of the 4 patients was with lobar collapse. The fourth patient presented with hyperinflation. We conclude that inflammatory endobronchial polyps may be associated with a history of mechanical ventilation in the neonatal period, polyp formation perhaps being secondary to airway trauma. The small caliber of the main airways in neonates may also be a contributory factor in presentation.

Bronchial Neoplasms↗

Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres--an open randomised crossover preference study.

Creon 10,000 Minimicrospherestrade mark (Creon) 10,000 MMS) is a pancreatic enzyme formulation that contains smaller spheres of pancreatin in a 50% smaller capsule than conventional microspheres (Creon) 8,000). This three-centre study investigated the preference of cystic fibrosis (CF) patients for these products. In one centre, 72 h stool fat excretion and coefficient of fat absorption (CFA) were also compared. Fifty-nine patients with a mean age 10 years (range 3-17) took Creon 8,000 ms for 14 days and were then randomised to 28 days of Creon 8,000 ms followed by 28 days of Creon 10,000 MMS, or vice versa. Dosing was lipase for lipase according to the labelled declaration. At the end of the second treatment period, 51 of 54 patients who completed the study expressed a preference, with a statistically significant preference in favour of Creon 10,000 MMS (47/51; 87%) vs. Creon 8,000 ms (4/51; 7.4%; P<0.0001). Stool fat (g/day) and CFA (%) were measured in 24 patients at the end of each treatment period: the products were therapeutically equivalent (Creon 10,000: 8.4 g/day, 91.3% CFA; Creon 8,000: 6.7 g/day, 93.5% CFA). Both products were well tolerated. In conclusion, in CF children we found a clear preference for Creon 10,000 MMS compared with Creon 8,000 ms with no difference in fat absorption between the two products. Creon 10,000s smaller capsules are easier to take and should aid patient compliance.

Administration, Oral↗

Primary ciliary dyskinesia: age at diagnosis and symptom history.

UNLABELLED: Age at diagnosis and the symptom history of children with primary ciliary dyskinesia (PCD) are described by reviewing the case notes in the paediatric PCD clinic. Mean age at diagnosis was 4.4 y despite a history of neonatal respiratory distress in 37/55 cases, situs inversus in 38/55 cases and early onset troublesome rhinitis in 42/55. CONCLUSION: Diagnosis of PCD is often delayed despite the presence of typical symptoms early in life. The key clinical features of unexplained neonatal respiratory distress, early onset rhinitis, situs inversus and a productive cough are highlighted, which, especially when occurring in combination, makes early referral for specific testing for PCD mandatory.

Adolescent↗

Are annual blood tests in preschool cystic fibrosis patients worthwhile?

AIM: To investigate whether routine annual assessment blood tests in cystic fibrosis (CF) patients under 5 years influence management. METHODS: Retrospective review of the results of the first annual assessment blood tests of patients with CF less than 5 years of age during a four year period (1995-99). Management changes were identified from a follow up letter to the general practitioner or local paediatrician. RESULTS: A total of 169 patients (100 female), median age 2.2 years (range 0.3-4.9) were identified. Venepuncture was successful in 93% of patients. Of the 32 individual blood parameters measured, the overall success rate in obtaining a result was 81%. Eleven per cent of patients underwent subsequent management changes, including liver ultrasound, fasting glucose, and a short course of iron. Of particular importance, vitamin A and E concentrations were low in 9% of patients, which prompted an increase in prescribed dose. CONCLUSIONS: These results support the recommendations for routine blood tests at annual review in preschool CF children. The results may help to rationalise which tests are performed and thus reduce laboratory costs.

Child, Preschool↗

Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis.

BACKGROUND: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). An alternative lower cost therapy is hypertonic saline (HS), which has been shown to improve lung function in short term studies. This study compares the costs and consequences of daily rhDNase with alternate day rhDNase and HS in children with CF. METHODS: In an open, randomised, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once daily 2.5 mg rhDNase, alternate day 2.5 mg rhDNase, and twice daily 5 ml 7% HS. Outcomes assessed included forced expiratory volume in 1 second (FEV(1)) and quality of life. All healthcare resource use was prospectively recorded for each patient. Unit costs were collected and combined with resource use data to give the total health service costs per patient for each treatment strategy. RESULTS: Daily rhDNase resulted in a significantly greater increase in mean FEV(1) than HS (8%, 95% CI 2 to 14) but there was no significant difference in FEV(1) between daily and alternate day rhDNase (2%, 95% CI -4 to 9). Over a 12 week period the mean incremental costs of daily rhDNase compared with HS was pound 1409 (95% CI pound 440 to pound 2318), and the incremental cost of using daily rather than alternate day rhDNase was pound 513 (95% CI - pound 546 to pound 1510). CONCLUSIONS: Daily rhDNase is more effective than 5 ml 7% HS twice daily delivered by jet nebuliser, but significantly increases healthcare costs. Administering rhDNase on an alternate day rather than a daily basis is as effective, with a potential for cost savings.

Adolescent↗

Difficult asthma in children.

Asthmatic children on high dose corticosteroids need to be fully assessed to ensure that such dosages are really necessary. Further work needs to be undertaken to find the best approach to poor treatment adherence and false claims for financial support. The benefits of particular components of specialist assessment need to be evaluated prospectively and multicentre collaboration is needed to evaluate phenotype specific treatment and new treatments for truly difficult asthma.

Adrenal Cortex Hormones↗

Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance.

BACKGROUND: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. METHODS: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. RESULTS: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3-920), 533.6 (80-2053), 491.3 (31-1140), and 716 (398-1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2-5.2), 5.4 (1.0-22.1), 2.6 (0.8-12.9), 10.7 (1.6-46.7), and 4.85 (2.5-18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. CONCLUSIONS: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD.

Adolescent↗

Airway function in infants newly diagnosed with cystic fibrosis.

The lung function of infants with cystic fibrosis is often reduced shortly after diagnosis. We measured the airway function of newly diagnosed infants to test whether this reduction is independent of clinically recognised lower respiratory illness. We compared the airway function of 33 infants with cystic fibrosis and 87 healthy controls after adjustment for sex, age, bodyweight and length, and exposure to maternal smoking. Airway function was significantly reduced in children with cystic fibrosis, even in those without clinically recognised previous lower respiratory illness. Our findings raise important questions about the onset and natural history of impaired airway function in infants with cystic fibrosis.

Case-Control Studies↗

Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial.

BACKGROUND: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis. METHODS: In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care. FINDINGS: Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments. INTERPRETATION: Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.

Adolescent↗

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone.

Exhaled nitric oxide (FE(NO)) has been proposed as a noninvasive marker of airway inflammation in asthma, and may reflect airway eosinophilia. We examined the relationship between FE(NO) and eosinophilic inflammation in endobronchial biopsies from 31 children with difficult asthma (mean age [range] 11.9 [6-17] yr), following 2 wk of prednisolone (40 mg/d). Endobronchial biopsy was also performed in seven children without asthma. Biopsy eosinophils were detected using antibody to major basic protein, and point-counting used to derive an "eosinophil score." FE(NO) readings and suitable biopsies for analysis were both obtained in 21 of 31 children with asthma. Adherence to prednisolone was demonstrated in 17 of these 21. Within this group, there was a correlation between FE(NO) and eosinophil score (r = 0.54, p = 0.03). The relationship was strongest in patients with persistent symptoms after prednisolone, in whom FE(NO) > 7 ppb was associated with a raised eosinophil score. For all patients, FE(NO) < 7 ppb was associated with an eosinophil score within the nonasthmatic range, regardless of symptoms. We propose that FE(NO) is associated with eosinophilic inflammation in children with difficult asthma, following prednisolone, and may help in identifying patients in whom persistent symptoms are associated with airway eosinophilia.

Administration, Oral↗

Tryptophan hydroxylase gene variant and smoking behavior.

Approximately 50% of the variance in smoking behavior is attributable to genetic factors. Genes in the serotonin system are plausible candidates because of serotonin's role in mood regulation. The present study examined the association of smoking behavior with a polymorphism in the TPH gene, which codes for a rate limiting enzyme in the biosynthesis of serotonin. A polymorphism in intron 7 has been linked with a variety of traits involving poor impulse control. Participants in this study were 249 Caucasian smokers and 202 nonsmokers recruited through newspaper advertisements. Smokers completed smoking history and nicotine dependence assessments. The overall frequencies of the A- and C-allele were 42% and 58%, respectively. There was no association of TPH alleles with smoking status. However, case series analysis indicated that individuals with the A/A genotype started smoking at age 15.6 years, compared with 17.3 years among smokers with other genotypes. This association was significant in a multivariate regression model controlling for age, education, body mass index (BMI), alcohol use, and medication use. This finding is consistent with previous studies relating the A-allele to impulsive behavior and suggests that it may predispose to early smoking initiation. Future family-based studies are needed to confirm this finding. Published 2001 Wiley-Liss, Inc.

Adult↗

Pulmonary artery occlusion from tuberculous lymphadenopathy in a child.

Occlusion of the pulmonary artery is a rare complication of mediastinal tuberculosis. We report on a 10-year-old girl who presented with a tuberculous pericardial effusion in whom subsequent imaging showed a totally occluded right pulmonary artery from tuberculous lymphadenopathy. Diagnosis was confirmed by polymerase chain reaction from a lymph node biopsy. Failure of medical therapy necessitated surgical reconstruction of her right pulmonary artery. Postoperatively she has normal perfusion of the right lung and normal lung function.

Arterial Occlusive Diseases↗

Cystic fibrosis and Down's syndrome: not always a poor prognosis.

A child developed a bronchiolitis-like illness and was found to have mosaic Down's syndrome (diagnosed on karyotype) and also cystic fibrosis, diagnosed on the basis of a high sweat osmolality (247 mosmoles/kg sweat; normal, 62-137) and a homozygous delta F508 genotype. Despite two potentially life-threatening conditions, the child is doing well at the age of 7 years, despite pancreatic insufficiency.

Bronchiolitis↗