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Biomedical subjects

H K Reddel

Publications and source records attributed to H K Reddel.

10 recordsLinked to original sources
PubMed2000

Optimal asthma control, starting with high doses of inhaled budesonide.

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1-16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200- and 1,600-microg x day(-1) starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with 3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16 (p=0.03) [corrected]. During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2 occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.

Administration, Inhalation↗
PubMed1998

Standardization of ambulatory peak flow monitoring: the importance of recent beta2-agonist inhalation.

Standardization of conditions for peak expiratory flow (PEF) monitoring is much more difficult in practice than for laboratory spirometry. Patients are usually asked to record PEF before medication. The aim of this study was to determine the effect of prior bronchodilator use on PEF outcome measures in a clinical trial. Electronic PEF records from 43 subjects with poorly controlled asthma were examined to determine the frequency with which beta2-agonist was inhaled <4 h before PEF measurement, as such PEF are potentially "postbronchodilator". The effect of inclusion of such PEF values on improvement in PEF outcome measures after 8 weeks of inhaled budesonide was calculated. Subjects were asked to record PEF before medication. During run-in, the median frequency of postbronchodilator PEF was 29%, falling to 0% after 8 weeks of budesonide. Inclusion of postbronchodilator PEF led to an overestimation of average morning, evening and daily PEF during run-in (p<0.001). Improvement in these indices with treatment was, therefore, underestimated. Minimum morning PEF expressed as per cent personal best was unaffected. Subjects may not be able to withhold beta2-agonist for 4 h before every peak flow reading. This may change as the level of asthma control changes, leading to a systematic bias in clinical trial end-points or inaccuracy in individual treatment decisions. Simple changes to peak expiratory flow instructions and analysis are proposed.

Administration, Inhalation↗
PubMed1998

Pitfalls in processing home electronic spirometric data in asthma.

Electronic spirometers offer the prospect of paperless home monitoring, but data quality is not automatically better than from conventional monitoring. The aim of this study was to determine the extent to which the quality and processing of self-recorded spirometric data from patients with asthma complied with international guidelines for spirometry. Data were from 33 subjects with poorly controlled asthma who had completed the first 9 weeks of a clinical budesonide trial. MicroMedical DiaryCard electronic spirometers were used to record three spirometric manoeuvres in twice-daily sessions. Confounding events were recorded in a paper diary. Within-session reproducibility was calculated for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) during the first week of run-in and week 9 of budesonide treatment. Geometric means of within-session reproducibility (mean difference between highest and second-highest value from each session over a one-week period) for FEV1, FVC and PEF were 76 mL, 116 mL and 18 L x min(-1), respectively, during run-in. Times of spirometric sessions varied widely, with some overlap between morning and evening session times. Manoeuvre-induced falls in PEF and FEV1 occurred only as often as expected by chance. Nonasthma events including equipment faults and painful conditions caused changes in spirometric results. Home spirometric monitoring can be carried out with excellent reproducibility in patients with asthma. However, quality-control issues are complex and an accompanying paper diary remains essential.

Adolescent↗
PubMed1995

Which index of peak expiratory flow is most useful in the management of stable asthma?

Calculation of diurnal peak expiratory flow (PEF) variability using values before and after bronchodilator is no longer possible for many asthmatic patients because they now use beta-agonists "as needed" for symptoms rather than regularly. This study assesses the usefulness of a number of alternative PEF indices as markers of airway liability in subjects with stable, although not necessarily well-controlled, asthma. Forty-six adult subjects completed a questionnaire about symptoms and treatment in the previous 3 mo. Spirometric function and airway hyperresponsiveness (AHR) were assessed; AHR was expressed as dose response ratio (DRR) (maximal percent fall in FEV1 divided by final dose of histamine). Subjects recorded PEF morning and evening, before and after bronchodilator (if used) for 2 wk. Nine different PEF indices were calculated. Diurnal variability (amplitude percent maximum) without bronchodilator was significantly less than diurnal variability with bronchodilator. Normal indices of PEF lability were found in 42% of subjects with reduced maximal midexpiratory flow (MMEF). Most of the PEF indices correlated strongly with DRR, and less strongly with symptom score and airway obstruction. Minimum morning prebronchodilator PEF over a week (expressed as percent recent best or percent predicted) is recommended as the best PEF index of airway lability in patients with stable asthma because it correlates strongly with AHR, patients are more likely to comply with a once-daily reading, the calculation is simple, and regular use of a beta-agonist is not required.

Adrenergic beta-Agonists↗
PubMed1989

Establishment of a human in vitro mesothelial cell model system for investigating mechanisms of asbestos-induced mesothelioma.

Normal human mesothelial (NHM) cells were transfected with a plasmid containing SV40 early region DNA. Individual colonies of transformed cells from several donors were subcultured for periods of 5 to 6 months and 60 to 70 population doublings (PDs) before senescence, in contrast to a culture lifespan of approximately 1 month and 15 PDs for NHM cells. One such culture, designated MeT-5A, escaped senescence and has been passaged continuously for more than 2 years. These cells had a single integrated copy of SV40 early region DNA in their genome, expressed SV40 large T antigen, and exhibited features of mesothelial cells including sensitivity to the cytotoxic effects of asbestos fibers. One year after injection subcutaneously or intraperitoneally in athymic nude mice, these cells remain nontumorigenic, and therefore are a potential model system for in vitro fiber carcinogenesis studies.

Animals↗