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Biomedical subjects

A Bush

Publications and source records attributed to A Bush.

At least 37 records · Page 2Linked to original sources

Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms.

BACKGROUND: The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. METHODS: The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RESULTS: RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. CONCLUSION: In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.

Adolescent↗

Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis.

BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.

Adolescent↗

Case-control study of Stenotrophomonas maltophilia acquisition in cystic fibrosis patients.

The aims of this case-control study were to describe the characteristics of cystic fibrosis (CF) patients who isolated Stenotrophomonas maltophilia in sputum, to determine risk factors for acquisition, to assess persistence of the organism and clinical outcomes postacquisition. Data were collected from 1991-1999. CF patients and controls (who had never isolated S. maltophilia) were matched for age (+/- 1 yr), sex and forced expiratory volume in one second (+/- 10%). Data were collected from the year prior and for 2 yrs postacquisition of S. maltophilia. The prevalence of S. maltophilia increased from 3.3% to 15%. Factors associated with S. maltophilia acquisition were more than two courses of intravenous antibiotics, isolation of Aspergillus fumigatus in sputum and oral steroid use. The effect of A. fumigatus was independent of steroid use. Clinical status did not change postacquisition. The majority of patients cleared the organism from the sputum. Long-term infection or an accelerated deterioration in lung function or nutrition is not likely post-Stenotrophomonas maltophilia acquisition in cystic fibrosis. This is the first documentation of an association between Aspergillus fumigatus isolation and Stenotrophomonas maltophilia acquisition in cystic fibrosis, independently of steroid therapy.

Adult↗

Normal nasal mucociliary clearance in CF children: evidence against a CFTR-related defect.

Studies on mucociliary clearance (MCC) in cystic fibrosis (CF) have produced conflicting results. This study aimed to differentiate primary (ion transport-related) from secondary (inflammatory) causes of delayed MCC in CF. Nasal MCC was measured in 50 children (CF, primary ciliary dyskinesia (PCD) and no respiratory disease). Nasal lavage fluid was analysed for interleukin (IL)-8 and tumour necrosis factor-alpha. Similar measurements were obtained in adult CF patients with and without chronic sinusitis (CS). Children with CF had neither delayed MCC nor increased levels of cytokines. Conversely, children with PCD had prolonged MCC times (all >30 min) and significantly raised levels of IL-8. CS-positive CF adults had significantly slower MCC than CS-negative subjects, but IL-8 levels were low and similar in both groups. Decreased airway surface liquid and delayed mucociliary clearance are the postulated primary mechanisms in cystic fibrosis. However, the current study reports that cystic fibrosis children have normal nasal mucociliary clearance. Abnormalities appeared in cystic fibrosis adults with symptoms of chronic sinus disease, suggesting a secondary rather than primary phenomenon. Studies to explore this mechanism in the distal, more sparsely-ciliated airways could aid an understanding of pathogenesis and the development of new treatments.

Adolescent↗

HRCT lung abnormalities are not a surrogate for exercise limitation in bronchiectasis.

In paediatric bronchiectasis, there has been limited work on the relationship between disease severity as assessed by exercise limitation and high resolution computed tomography (HRCT). An observational study was performed on 36 children who completed a questionnaire, physical examination, spirometry and sputum analysis, followed by a low dose of radiation protocol chest computed tomography (CT) scan and cycle ergometry incremental exercise test. A modified Bhalla score was used to score the HRCT abnormalities. The exercise variables used to assess functional status were heart rate, oxygen consumption, oxygen saturations and time of exercise. The results were compared with established normal paediatric values. The median (range) age of the children was 13 yrs (10.6-17.1). Age, sex, height, weight or pubertal status were equally distributed between the children with cystic fibrosis (CF) or non-CF bronchiectasis. The children with non-CF bronchiectasis had a lower median forced expiratory volume in one second % predicted than the children with CF (69% versus 76%, respectively). The distribution of lung disease differed between the two groups. The children with CF bronchiectasis had predominantly right upper lobe disease, and scored higher for the presence and extent of bronchiectasis. Otherwise, there was no statistical difference in the overall CT score or the individual CT parameters between the groups. There was evidence of exercise limitation in both CF and non-CF bronchiectasis compared to normal children. No consistent relationships were identified between the lung function parameters, HRCT findings or exercise parameters in either disease group. In this study, high resolution computed tomography features were not found to be markers of exercise capacity. As spirometry, high resolution computed tomography features and exercise testing give different information in children with cystic fibrosis and non-cystic fibrosis bronchiectasis, the current authors suggest all three may be required for the comprehensive assessment of respiratory status.

Adolescent↗

Three-minute step test to assess exercise capacity in children with cystic fibrosis with mild lung disease.

The information obtained from a simple submaximal test (the 3-min step test) was compared with that from a maximal cycle ergometry study, in a group of children with CF with relatively mild abnormalities of lung function (FEV(1) > 50% predicted). Nineteen subjects with CF undertook both exercise tests on the same day. Measurements included heart rate (HR), oxygen saturations (SaO(2)), visual analogue score of perceived breathlessness (VAS), 15-count breathlessness score (15c), and peak oxygen consumption (VO(2)). There were significant differences in the median changes in HR and VAS during the cycle test compared to the step test, 78 vs. 46 beats per minute (P < 0.05) and 51 mm vs. 42 mm (P < 0.05), respectively. There were no differences between median changes in 15c and SaO(2), but 3 subjects had significant desaturations (>4%) during the cycle test only. Significant exercise desaturations may occur in mild CF lung disease and will not be detected by a 3-min step test. The 15c did not discriminate between a maximal and a submaximal test, and was less useful than VAS. Important information may be missed by the step test which is detected by more complex exercise tests.

Adolescent↗

Multiresistant Pseudomonas aeruginosa in a pediatric cystic fibrosis center: natural history and implications for segregation.

It has been suggested that cystic fibrosis (CF) patients harboring multiresistant (MR) Pseudomonas aeruginosa (PA) should be seen in separate clinics. The aim of this study was to test the feasibility of this by longitudinally studying the consistency of isolates of MRPA in individuals. We analyzed all respiratory tract cultures undertaken in 1 year from a pediatric CF clinic population (n = 367). PA was classified as MR according to the definition of the American CF Foundation: resistance to all agents in at least two of the following groups of antibiotics: beta-lactams, aminoglycosides, and fluroquinolones. PA was cultured from 96 children during the year of study. Thirty-six were infected with at least one MR strain. Following initial identification of MRPA, MR in subsequent cultures was highly variable. Twenty-three of 36 patients had subsequent cultures in which PA was identified. However, 21 of 23 patients had at least one isolate that was not MR following detection of MRPA. The variability with time in isolation of MR strains from individuals demonstrates the potential difficulties in designing segregation policies based on antibiotic sensitivity patterns.

Adolescent↗

Oral health and related factors in cystic fibrosis and other chronic respiratory disorders.

AIM: To compare the prevalence of dental caries, dental calculus, and enamel defects in children with cystic fibrosis (CF) and children with other chronic respiratory disorders. METHODS: A cross sectional observational survey. One examiner (AN) undertook oral examinations to assess dental caries, periodontal health, and enamel defects in children attending respiratory outpatient clinics. RESULTS: A total of 74 patients with CF (35 male; mean age 10.7 years, range 2.5-16.5) were compared with a control group of 106 patients with other chronic respiratory disorders (52 male; mean age 9.1 years, range 3.0-16.5). There were significantly more defects of enamel in the permanent teeth of CF patients, compared with the teeth of those children with other chronic respiratory disorders. In addition, non-significant trends towards a lower caries prevalence in both dentitions, increased numbers of sextants with calculus deposits, and a reduced number of healthy gingival sextants were observed in the patients with cystic fibrosis. CONCLUSIONS: Enamel defects, particularly enamel opacities, which can be disfiguring, are more common in CF patients. Early, regular dental visits may prevent such defects becoming dentally disabling and would also permit the removal of dental calculus deposits. The use of long term antibiotics and pancreatic enzymes may confer some protection against the development and progression of dental caries in patients with cystic fibrosis. The inclusion of a specialist paediatric dentist, as part of the multiprofessional team managing the care of these children, would be an advantage.

Adolescent↗

Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count.

BACKGROUND: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. METHODS: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively). CONCLUSIONS: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Adolescent↗

The safety and quality of endobronchial biopsy in children under five years old.

BACKGROUND: Little is known about the airway pathology of wheezing disorders in infants and preschool children, partly owing to the difficulty of undertaking invasive studies in this age group. The safety of endobronchial biopsy and the quality of biopsies obtained were reviewed in infants and preschool children. METHODS: Case notes of children under five years of age who underwent bronchoscopy and endobronchial biopsy were reviewed. The safety of the procedure was compared in a control group matched for weight and age, undergoing bronchoscopy without endobronchial biopsy. A consultant histopathologist assessed biopsy quality. RESULTS: 33 patients (mean age 31 months, range 4 to 59) underwent bronchoscopy and endobronchial biopsy, and were matched with 33 controls (mean age 28 months, range 3 to 52). There was no significant difference between groups in the number, type, or severity of complications occurring during or after the procedure. Biopsies from 30 of the 33 subjects could be assessed. Reticular basement membrane was identified in all 30; inflammation could be assessed in 26; areas of smooth muscle were present in 23. CONCLUSIONS: In a group of preschool children undergoing bronchoscopy under general anaesthetic, performance of endobronchial biopsy carried no extra risk. The quality of biopsies obtained was usually sufficient to allow an assessment of remodelling and inflammation.

Biopsy↗

Flexible endoscopy of paediatric airways.

Paediatric fibreoptic bronchoscopy is used for ever wider indications, and increasingly used in many contexts, including paediatric and neonatal intensive care. The report of this Task Force contains an overview on the current applications of paediatric bronchoscopy. The report discusses the facilities and equipment needed for the procedure, including the newly developed bronchoscopes which are allowing intervention even in very small children. The indications of both flexible and rigid bronchoscopes in the context of newer and smaller flexible endoscopic equipment are also considered. The care of the instruments, including disinfection and sterilisation, is fully documented. Patient management is described, including the relative merits of conscious sedation and general anaesthesia, as well as special settings for the procedure, including the needs in intensive care. Special procedures, increasingly performed bronchoscopically are described. These include bronchoalveolar lavage, endobronchial and transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of bronchoscopic procedures, including bronchoscopic research in children. Advances in instrumentation, and also improved anaesthetic techniques, allow fibreoptic bronchoscopy to be safely performed in even very small, sick infants, provided proper precautions are taken.

Airway Obstruction↗

Airway surface pH in subjects with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator protein can transport bicarbonate and may therefore regulate airway surface (AS) pH. Disturbances of AS pH could contribute to the pathophysiology of CF lung disease. Five studies were carried out including the following: study 1) nasal pH measurements were made in 25 CF and 10 non-CF adults using an antimony pH probe. Mean nasal pH was significantly lower in the CF group. Nasal potential difference may have been a confounding factor; study 2) in a fresh cohort of CF and non-CF subjects, no significant difference was found between the two groups using a gold pH probe; study 3) simultaneous nasal pH measurements were made in 15 CF and 15 non-CF adults using both probes. In the CF group, there was a trend for the antimony probe to read lower than the gold probe. In the non-CF group, the antimony probe read higher. The pH difference noted in study 1 related to technical factors; study 4) the effect of acute changes in serum acid/base balance on nasal pH was assessed in five non-CF adults. Nasal pH was not altered by either acute respiratory acidosis or alkalosis; study 5) nasal and lower airway pH was measured in five CF and six non-CF children. No difference was found between the groups. There was a correlation between nasal and lower airway pH. The authors conclude that airway surface pH does not differ between cystic fibrosis and noncystic fibrosis subjects and therefore, cystic fibrosis transmembrane conductance regulator may not play a major role in airway surface pH in vivo.

Adolescent↗

To clip or not to clip? Noseclips for spirometry.

The use of noseclips for open-circuit spirometry is sporadic, despite guidelines encouraging their use. The authors aimed to evaluate whether noseclips significantly affected measurements of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in children attending a tertiary, paediatric respiratory centre. Children attending the asthma and cystic fibrosis (CF) clinics were asked to perform two sets of spirometry, one with and one without noseclips in random order, 20-min apart. Paired data was obtained on 62 patients (32 asthma, 30 CF) with a median age of 11.4 yrs (range 7.2-17.2 yrs). There were no systematic differences in FEV1 or FVC measured with and without noseclips, although seven children (11%) had clinically significant differences in FEV1 of >190 mL. There is no clear advantage to wearing noseclips when performing open-circuit spirometry. Individuals should be assessed to ascertain their optimal technique, which should then be used consistently in clinical practice. Noseclips should probably be retained for research protocols.

Adolescent↗

Appendicular fractures: a significant problem among institutionalized adults with developmental disabilities.

A high incidence of nontraumatic fracture in adults with developmental disabilities living in a state-run facility was described. Risk factors for fracture, including bone mineral density (BMD), were investigated to determine whether people at highest risk for fracture could be prospectively identified. There was a 7.3% incidence of fracture among 391 adults. Risk factors were examined for 23 residents with fracture and 23 age-, race-, and gender-matched controls. There was a trend for antiepileptic medication usage to be associated with fractures. Estimated BMD by heel ultrasound did not predict fracture; however, values were much lower than those for the general population. Fractures and low BMD are significant problems among institutionalized adults with severe developmental disabilities. Further studies to identify therapies to prevent fractures are warranted.

Adolescent↗