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Biomedical subjects

D N Payne

Publications and source records attributed to D N Payne.

At least 19 recordsLinked to original sources
PubMed2006

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with DA.

Adolescent↗
PubMed2006

Investigation of young children with severe recurrent wheeze: any clinical benefit?

The management of young children with severe recurrent wheeze is difficult because symptoms are often refractory to conventional asthma therapy and other diagnoses must be excluded. The present authors aimed to evaluate the outcome of detailed, invasive investigations in such patients. Children aged between 3 months and 5 yrs with severe recurrent wheezing, who had been referred to a tertiary centre, underwent a protocol of investigations including a chest computed tomography scan, blood tests, nasal ciliary brushings, fibreoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial biopsy and passage of an oesophageal pH probe. A total of 47 children (25 males) with a median age of 26 (range 5-58) months underwent investigation. Of these, 39% were atopic, two-thirds had evidence of gastro-oesophageal reflux and 37 out of 47 had an abnormal bronchoscopy. Findings included structural abnormalities (13 out of 37), excessive mucus (20 out of 37) and macroscopic inflammation (10 out of 37). BAL revealed bacterial growth in 12 out of 44 (27%) patients. Good quality endobronchial biopsies were obtained from 36 out of 46 (78%) patients; of these, 44% had tissue eosinophilia and 28% had a thickened reticular basement membrane. Additional investigations (including bronchoscopy) in young children with severe wheeze may help to identify positive diagnoses and provide information to support a clinical diagnosis of asthma. This hypothesis-generating work should form the basis of future interventional studies.

Asthma↗
PubMed2005

Single-mode plane-polarized ytterbium-doped large-core fiber laser with 633-W continuous-wave output power.

We demonstrate a cladding-pumped single-mode plane-polarized ytterbium-doped fiber laser generating 633 W of continuous-wave output power at 1.1 microm with 67% slope efficiency and a polarization extinction ratio better than 16 dB. The laser is end pumped through both fiber ends and shows no evidence of roll-over, even at the highest output power, which is limited only by the available pump power.

Journal Article↗
PubMed2005

Single-frequency, single-mode, plane-polarized ytterbium-doped fiber master oscillator power amplifier source with 264 W of output power.

We present a single-frequency, single-mode, plane-polarized ytterbium-doped all-fiber master oscillator power amplifier source at 1060 nm generating 264 W of continuous-wave output power. The final-stage amplifier operated with a high gain of 19 dB and a high conversion efficiency of 68%. There was no evidence of rollover from stimulated Brillouin scattering even at the highest output power, and the maximum output was limited only by the available pump power.

Journal Article↗
PubMed2001

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↗
PubMed2001

Difficult asthma: defining the problems.

A retrospective survey was undertaken of children with difficult asthma, attending a respiratory clinic. The clinical and laboratory profiles of asthmatic children who were poorly controlled on > or = 800 microg of inhaled corticosteroids (ICS) were studied and compared to children well-controlled on > or = 800 microg ICS. Assessments were made of atopy, growth, lung function, treatment adherence, home environment, and responsiveness to corticosteroids (CS). Fiftyseven "difficult" and 23 well-controlled children were studied. Significant differences in the home environment were identified. Smoking was significantly more common in the difficult-to-control group. Nine children had alternative diagnoses. Poor CS responsiveness was present in 10 children. Adverse home environments, poor treatment supervision, alternative diagnoses, and unresponsiveness to CS were the most important factors in difficult asthma. A full assessment, including bronchoscopy, is indicated to avoid unnecessary increases in CS to doses that could cause side-effects.

Administration, Inhalation↗
PubMed2001

Asthma severity and inflammation markers in children.

UNLABELLED: The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any METHOD: Neither did any marker of airway inflammation relate to recent symptoms, unlike PC20, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s (FEV1) and both NO and sputum ECP (r=-0.46, p=<0.001; r=-0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV1 (PC20) (r=-0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.

Adolescent↗
PubMed2001

Molecular mechanisms of corticosteroid actions.

Glucocorticoids are the most effective therapeutic agents used for the treatment of chronic inflammatory diseases of the lung. They act by interacting with, and thereby activating, a specific cytoplasmic receptor (GR) which then migrates to the cell nucleus and inhibits inflammatory gene transcription. Inflammatory gene transcription is enhanced by activation of several intracellular signalling pathways which activate transcription factor such as NF-kappaB and AP-1. These transcription factors bind to DNA and induce local unwinding of the DNA structure allowing increased gene transcription. Glucocorticoids interfere with the ability of NF-kappaB and AP-1 to induce transcription by increasing the compaction of unwound chromosomal DNA in a process that involves deacetylation of histone proteins. A small number of asthmatic patients are resistant to the beneficial effects of glucocorticoids. This defect does not appear to be due to a reduced expression of GR but may be associated with a failure of GR to translocate into the nucleus and/or a reduced ability to inhibit AP-1 actions.

Anti-Inflammatory Agents↗
PubMed2001

Children with difficult asthma: a practical approach.

Many open studies investigating the effects of innovative treatments for steroid-dependent asthma demonstrate some benefit. This is also true of the majority of placebo arms in placebo-controlled trials. This suggests that children with difficult asthma benefit from the high level of input that is typically provided in clinical trials, with or without additional medication. Such intensive management of patients, with the emphasis on establishing the diagnosis, improving adherence, and identifying provoking factors, is the key to optimizing asthma control for these children. For patients with genuinely severe asthma, despite high doses of conventional treatment, a greater understanding of the pathological basis of persistent symptoms is needed. Identification of different pathological subtypes of severe asthma should allow for more rational prescribing of asthma therapy, as well as the design of further trials of potential steroid-sparing treatments.

Administration, Inhalation↗
PubMed2001

Evidence for different subgroups of difficult asthma in children.

BACKGROUND: Children with difficult asthma experience frequent symptoms despite treatment with high dose inhaled steroids. Persistent symptoms may result from persistent airway inflammation which can be monitored by measuring exhaled nitric oxide (NO). This study aimed to assess the role of airway inflammation, using NO as a surrogate, in children with difficult asthma and to investigate the response to oral prednisolone. METHODS: NO was measured in 23 children (mean age 11.7 years) with difficult asthma, before and after 2 weeks of treatment with oral prednisolone. The clinical response was assessed by spirometric tests, peak flow, bronchodilator use, and symptoms. Adherence to treatment was assessed by measuring serum prednisolone and cortisol concentrations. NO was measured in 55 healthy children to establish a normal range. RESULTS: NO concentrations were higher in asthmatic patients than in controls (geometric mean 11.2 v 5.3 ppb, p<0.01). Using grouped data, the concentration of NO fell following prednisolone (11.2 v 7.5 ppb, p<0.01) accompanied by an improvement in morning peak flow (p<0.05). The baseline NO concentration was raised (>12.5 ppb) in nine asthmatic patients and remained high after prednisolone in five. Thirteen had normal levels of NO (<12.5 ppb) before and after prednisolone. Thirteen asthmatic patients remained symptomatic following prednisolone; NO levels were raised on both occasions in five of these and were normal in seven. CONCLUSIONS: As a group, the asthmatic subjects demonstrated evidence of airway inflammation which responded to prednisolone. At least two subgroups of patients were identified: one with persistently raised NO levels despite treatment with oral prednisolone indicating ongoing steroid insensitive inflammation, and another with normal levels of NO. Both subgroups included patients with persistent symptoms, which suggests that different patterns of difficult asthma in children exist.

Adolescent↗
PubMed1999

An evaluation of the suitability of the European suspension test to reflect in vitro activity of antiseptics against clinically significant organisms.

The effectiveness of four antiseptics representing soluble phenolics (Dettol), Quaternary Ammonium Compounds (QAC) (Dettol Hospital Concentrate: DHC), mixed QAC/chlorhexidine (Hibicet Hospital Concentrate: HHC) and povidone iodine (Betadine) was assessed using the proposed phase 2 step 1 European Suspension test. The in vitro activity of the antiseptics against two of the proposed challenge strains, i.e. Staphylococcus aureus and Pseudomonas aeruginosa, was compared with that of 14 problematic clinical isolates of bacteria from a range of genera, including some multiple antibiotic resistant strains, and a clinical isolate of Candida albicans. In addition to the 5 min contact time recommended in the European test, a 1 min time was included. All four products, at their recommended use dilutions and a contact time of 5 min, achieved a Microbicidal Effect (ME) log reduction of at least 5 against the majority of organisms. Differences in activity between products were more pronounced and therefore the tests more discriminatory, when the contact time was reduced to 1 min. The clinical strains were not overtly more resistant to antiseptics than the standard test strains, suggesting that the CEN test strains mimic the antiseptic susceptibility of clinical isolates.

Anti-Infective Agents, Local↗
PubMed1998

Use of the Malthus-AT system to assess the efficacy of permeabilizing agents on the activity of antibacterial agents against Pseudomonas aeruginosa.

The Malthus-AT system provided a satisfactory method for examining the effects of permeabilizing agents on the activity of sub-inhibitory concentrations of antibacterial agents against Pseudomonas aeruginosa G48. Under this system, disodium edetate potentiated the activity of chlorhexidine diacetate (CHA), cetylpyridinium chloride, para-chlorometaxylenol and triclosan. Nitrilotriacetic acid enhanced the activity of some of the antibacterials tested, whereas sodium polyphosphate markedly reduced the efficacy of CHA.

Anti-Bacterial Agents↗
PubMed1998

Effect of permeabilizing agents on antibacterial activity against a simple Pseudomonas aeruginosa biofilm.

A simple Pseudomonas aeruginosa G48 biofilm on stainless steel discs provided a useful primary screen of potentiating effects of various permeabilizing agents on antibacterial agents. Experiments with Ps. aeruginosa suspensions could not be used to predict the effects of biocides and permeabilizers on biofilms. Although antibacterial activity against biofilms was less than demonstrated in suspension tests, potentiation by some permeabilizers was still observed.

Anti-Infective Agents, Local↗
PubMed1998

Antiseptics: a forgotten weapon in the control of antibiotic resistant bacteria in hospital and community settings?

The aim of this study was to ascertain the activity of a selection of widely-used antiseptic/disinfectant agents against antibiotic resistant bacteria and strains isolated from patients infected with clinically significant species. Four antiseptic agents (Dettol, Dettol Hospital Concentrate, Savlon and Betadine) were tested against Staphylococcus aureus, Methicillin Resistant S. aureus (MRSA), Enterococcus hirae, Vancomicin Resistant Enterococcus sp (VRE), Escherichia coli and E. coli 0157. The antiseptics were applied at recommended use dilutions and at a half and a quarter of those concentrations in a standard suspension test (EST). Organic material was added to mimic the presence of blood, protein and other such contaminants to be found in the clinical situation. All antiseptics tested were effective against both the antibiotic sensitive and antibiotic resistant strains of S. aureus and E. hirae as well as normal and clinical strains of E. coli at recommended concentrations. All but Betadine were also effective against the antibiotic resistant bacteria at a half and a quarter of normal concentration. The iodine containing antiseptic, however, failed the test against MRSA at a half normal concentration and showed virtually no activity against MRSA at a quarter normal concentration.

Anti-Infective Agents, Local↗