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Biomedical subjects

C R Jenkins

Publications and source records attributed to C R Jenkins.

At least 19 recordsLinked to original sources
PubMed2006

Double blind randomised controlled trial of two different breathing techniques in the management of asthma.

BACKGROUND: Previous studies have shown that breathing techniques reduce short acting beta(2) agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. METHODS: After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. RESULTS: Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. CONCLUSION: Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises.

Administration, Inhalation↗
PubMed2005

Accuracy of central venous pressure monitoring during simultaneous continuous infusion through the same catheter.

Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.

Adult↗
PubMed2005

Traditional and patient-centred outcomes with three classes of asthma medication.

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.

Acetates↗
PubMed2004

When can personal best peak flow be determined for asthma action plans?

BACKGROUND: Written asthma action plans based on personal best peak expiratory flow (PEF) consistently improve health outcomes, whereas those based on predicted PEF do not. Guidelines state that personal best PEF should be assessed over 2-3 weeks during good asthma control, but it is unclear how long to wait after commencing or changing treatment. METHODS: Electronically recorded spirometric data from 61 subjects with initially poorly controlled asthma from a 72 week budesonide study were analysed. For each week, average morning pre-bronchodilator PEF was calculated and personal best PEF was determined as the highest PEF in the previous 2 weeks. The time to plateau was defined as the week beyond which no further improvement occurred. RESULTS: At baseline, average morning PEF was 61% predicted and personal best PEF was 87% predicted. Personal best PEF from twice daily monitoring increased to a plateau of 95% predicted (p<0.0001) after only 3 weeks of budesonide treatment. However, average morning PEF continued to improve for 3 months and "as needed" reliever use for 7 months. CONCLUSIONS: Personal best PEF is a useful concept for asthma self-management plans when determined as the highest PEF over the previous 2 weeks. With twice daily monitoring, personal best PEF reaches plateau levels after only a few weeks of corticosteroid treatment.

Adolescent↗
PubMed2001

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.

Adult↗
PubMed2001

Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids.

To determine predictors for failed reduction of inhaled corticosteroids (ICS), in 50 subjects with well-controlled asthma (age 43.7 [18-69]; 22 males) taking a median dose of 1,000 microg ICS/d (100-3,600 microg/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation test (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflammatory cells were measured at baseline and at monthly intervals. Thirty-nine subjects suffered an asthma exacerbation. Seven subjects were successfully weaned off ICS. Using a Kaplan- Meier survival analysis, the significant predictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive to mannitol during the dose-reduction phase of the study (p = 0.02). Subjects older than 40 yr of age tended to be at greater risk of ICS reduction failure (p = 0.059). Response to mannitol and percentage sputum eosinophils were significantly greater before a failed ICS reduction than before the last successful ICS reduction, whereas there were no significant differences in symptoms, spirometry, or eNO. These findings suggest that documentation of patient's AHR or sputum eosinophils may be useful in guiding the reduction of ICS doses.

Adolescent↗
PubMed2001

Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.

Adult↗
PubMed2000

Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma.

There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.

Administration, Inhalation↗
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↗