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Biomedical subjects

Peter G Gibson

Publications and source records attributed to Peter G Gibson.

At least 37 records · Page 2Linked to original sources

Induced sputum 8-isoprostane concentrations in inflammatory airway diseases.

Induced sputum 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) concentrations may be a useful marker of oxidative stress in airways disease. This study examines oxidative stress (measured by 8-iso-PGF(2alpha)) in airway disease according to disease type (asthma and bronchiectasis), disease activity (stable and acute asthma), and disease pattern (intermittent, mild, moderate, and severe persistent asthma). We compared subjects with stable asthma (n = 71) and bronchiectasis (n = 23) with healthy control subjects (n = 29). Another group of patients with asthma (n = 39) were assessed during and after acute exacerbation. Induced sputum 8-iso-PGF(2alpha) concentrations were validated and found to be elevated in subjects with stable asthma and bronchiectasis versus control subjects (median [interquartile range] 216 [103-389] and 698 [264-1,613] ng/L vs. 123 [41-290] ng/L, p < 0.001) and increased as clinical asthma pattern worsened (intermittent 115 [42-153], mild persistent 116 [89-229] ng/L, moderate persistent 183 [110-317] ng/L, severe persistent 387 [102-587] ng/L; p = 0.010). Sputum 8-iso-PGF(2alpha) concentrations were elevated during acute asthma and decreased with recovery (458 [227-950] ng/L vs. 214 [148-304] ng/L, p = 0.0002). We conclude that 8-iso-PGF(2alpha) is involved in the pathophysiology of inflammatory airway diseases, being related to disease type, pattern, and activity. Analysis of 8-iso-PGF(2alpha) concentrations in induced sputum provides a useful tool for monitoring oxidative stress and investigating strategies aimed at reducing oxidative stress in airways disease.

Adult↗

Randomized controlled trial of a teacher-led asthma education program.

Our objective was to determine whether an asthma education program in schools would have 1) a direct impact on student knowledge and attitudes to asthma and quality of life of the students with asthma, 2) an indirect impact on teacher knowledge and attitudes to asthma and on school policies about asthma, and 3) a sustainable program after the resources to implement the research were withdrawn. Seventeen intervention and 15 control schools participated in a controlled trial. Baseline knowledge and attitudes were measured in year 8 students (ages 13-14 years) and their teachers together with quality of life in the students with asthma. A three-lesson package about asthma was delivered by teachers as part of the Personal Development/Health/Physical Education (PD/H/PE) curriculum. Follow-up questionnaires were administered to students and staff. Efforts to change school policies were documented. Five years after the intervention, PD/H/PE teachers were contacted to determine whether the program was still operating. Main outcome measures included asthma knowledge, attitudes, and quality of life. Questionnaires were returned by 4,161/4,475 of the year 8 students at baseline and by 3,443 at follow-up. In intervention schools, compared with control schools, students showed improved asthma knowledge (P < 0.0001), improvement in tolerance to asthma (P = 0.02), internal control (P = 0.03), and less tendency to believe in the role of chance in asthma control (P = 0.04). Students from intervention but not control schools showed significant improvements in overall quality of life (P = 0.003 vs. P = 0.82, respectively). Teachers from intervention schools showed significant increases in knowledge compared to control schools (P < 0.0001). Intervention schools were more likely to seek further health education about asthma (P < 0.01). Five years after the 35 schools involved in the development of the materials or the trial had been offered the Living With Asthma package, 25 (71%) were still teaching the program to most or all of their students. Fifty-nine of the 61 (97%) high schools in the Hunter Region now have the program. Management and distribution of the Living With Asthma program have been taken over by the Asthma Foundation of New South Wales. The package has been updated and is being offered to all high schools throughout New South Wales as part of the National Asthma-Friendly Schools Project. In conclusion, a teacher-led asthma education program in secondary school had direct and indirect beneficial outcomes and was sustained at a high level for 5 years in most schools in the Hunter Region, despite minimal ongoing maintenance and support from health workers.

Adolescent↗

Role of atypical bacterial infection of the lung in predisposition/protection of asthma.

Asthma is a common inflammatory disease of the airways that results in airway narrowing and wheezing. Allergic asthma is characterised by a T-helper cell-type (Th) 2 response, immunoglobulin (Ig) E production, and eosinophilic influx into the airways. Recently, many clinical studies have implicated Mycoplasma pneumoniae and Chlamydia pneumoniae in the development and exacerbation of both chronic and acute asthma. It is widely accepted that M. pneumoniae and C. pneumoniae infections require Th1 immunity for clearance; therefore, according to the hygiene hypothesis, these infections should be protective against asthma. Here, we review the clinical evidence for the association and mechanisms of predisposition to and protection against asthma by these infections. We will examine the following question: Is it the absence of infection or the age of the individual on infection that confers susceptibility or resistance to asthma and does this vary between normal and predisposed individuals? We put forward a hypothesis of the effects of these infections on the development and prevention of asthma and how novel preventative and treatment strategies involving these microbes may be targeted against asthma.

Adrenal Cortex Hormones↗

Maternal asthma is associated with reduced female fetal growth.

Asthma during pregnancy is associated with a low birth weight, although the mechanisms contributing to this outcome remain unknown. The relationship between maternal asthma and its treatment, placental function, fetal sex, and low birth weight was examined to establish the effect of asthma on fetal growth. Glucocorticoid intake by women with asthma was assessed throughout pregnancy. The placenta was collected after delivery, and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was measured. Fetal cortisol and estriol were measured in the umbilical vein plasma at delivery. Those with asthma were compared with a nonasthmatic control group. In women with asthma who did not use inhaled steroids and were pregnant with a female fetus, we observed significantly reduced birth weights, whereas male birth weights were unaffected. The presence of a female fetus was associated with significantly increased maternal circulating monocytes, significantly reduced placental 11beta-HSD2 activity and fetal estriol, and a trend toward elevated fetal plasma cortisol. This study provides evidence that in pregnancies complicated by asthma there is a fetal sex-specific effect on the maternal immune system with adverse effects on placental function and female fetal growth.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Inhaled corticosteroid doses in asthma: an evidence-based approach.

OBJECTIVE: To define the evidence for doses of inhaled corticosteroids in asthma and describe this in clinically meaningful, evidence-based terms. DATA SOURCE: Cochrane Database of Systematic Reviews. STUDY SELECTION AND DATA EXTRACTION: We identified systematic reviews of randomised controlled trials of dosing of inhaled corticosteroids in asthma. Data on efficacy and safety of different doses were extracted from meta-analyses and summarised as the number needed to treat (NNT) and number needed to harm (NNH). DATA SYNTHESIS: Inhaled corticosteroids were highly efficacious, with a relatively flat dose-response curve. Three patients needed to be treated with fluticasone 100 microg daily to prevent worsening asthma (NNT 3), and for fluticasone 1000 microg the NNT was 2.1 patients. The dose-response curve for side effects was steep. For a dose of fluticasone 100 microg, oral candidiasis developed in one of every 90 subjects treated (NNH 90). In contrast, the NNH for fluticasone 1000 microg and 2000 microg daily were 23 and 6, respectively. CONCLUSION: Level 1 evidence supports the use of low-dose inhaled corticosteroids in asthma. Clinicians should review doses of inhaled corticosteroids used for treating patients with asthma.

Administration, Inhalation↗

Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation.

The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.

Adolescent↗

Clinical usefulness of inflammatory markers in asthma.

Asthma is a significant and increasing health problem. Airway inflammation and hyperresponsiveness are key pathophysiological mechanisms underlying asthma. Currently, effective treatments target these two processes and can lead to clinically important improvements in disease control. At present, decisions to initiate or modify therapy are based on symptoms and measures of airway caliber, with no direct assessment of airway inflammation or hyperresponsiveness. It is now possible to measure airway inflammation using noninvasive markers such as exhaled gases, induced sputum and serum measurements. Exhaled nitric oxide (eNO) and induced sputum eosinophils show the greatest promise as clinically useful markers of airway inflammation in asthma. Induced sputum can now be applied to the diagnosis of airway diseases, based on its ability to detect eosinophilic bronchitis in cough, and to differentiate between eosinophilic and non-eosinophilic asthma. The place of induced sputum and eNO in the ongoing monitoring of patients with asthma are now being investigated in controlled trials.

Asthma↗

Asthma education.

Education about asthma and self-management of asthma are now key recommendations of asthma management guidelines. A Cochrane systematic review of 12 RCTs found that limited education programmes that offer information about asthma but not self-management skills did not reduce hospitalisation rates or visits to the doctor for asthma. The positive outcomes from limited asthma education were a reduction in symptoms. Asthma self-management education which consists of information, self-monitoring, regular medical review, and a written action plan is effective and leads to a reduction in hospitalisation and ER visits for asthma, unscheduled doctors visits, days lost from work, episodes of nocturnal asthma, indirect costs and an improvement in quality of life. The effects were large enough to be of both clinical and statistical significance. While a structured asthma self-management programme is effective in a hospital setting, attempts to deliver these programmes in primary care have met with varying success.

Asthma↗

Use of induced sputum for the diagnosis of influenza and infections in asthma: a comparison of diagnostic techniques.

BACKGROUND: Influenza (Flu) and respiratory syncytial virus (RSV) are important viral pathogens that cause lower respiratory tract infections and severe exacerbations of asthma. Molecular biological techniques are permitting a rapid and accurate diagnosis of infections caused by respiratory pathogens, and have typically been applied to upper respiratory samples. Sputum induction provides an opportunity to directly sample secretions from the lower respiratory tract. OBJECTIVES/STUDY DESIGN: To determine the role of induced sputum reverse-transcription polymerase chain reaction (RT-PCR) in the detection of respiratory pathogens and compare this with detection using serology and immunofluorescent antigen (IFA) testing, we recruited 49 adults from emergency room with exacerbations of asthma. After a medical assessment and spirometry, sputum was induced using ultrasonically nebulised normal saline. Sputum was assayed using IFA and RT-PCR for flu and RSV. Flu serology was performed acutely and at convalescence, 4-5 weeks later. RESULTS: Influenza A or B was detected in 24% of the samples by PCR, significantly more than the nine cases detected using serology and the one case using IFA (P<0.05). RSV was detected in 37% of samples using PCR and 20% by IFA (P<0.05). CONCLUSION: The combination of induced sputum and RT-PCR provides a useful means of detecting respiratory infection. The technique is safe in both adults and children, and RT-PCR is more sensitive than conventional serology and IFA. The improved sensitivity of induced sputum RT-PCR also permits a more rapid diagnosis and the opportunity of early administration of effective treatments.

Acute Disease↗

Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthma.

OBJECTIVE: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. METHODOLOGY: HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful. RESULTS: There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. CONCLUSION: Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.

Adult↗

Relationship between cough, cough receptor sensitivity and asthma in children.

In childhood asthma, cough is a major symptom in some but not in others. There is only limited data on the frequency, severity and prevalence of cough in children with classical asthma. Studies have largely shown no relationship between cough frequency and cough receptor sensitivity with various asthma severity indices. However relating cough severity with asthma severity is limited by various methodological and sensitivity issues, and these are presented in this paper. Mild asthma exacerbations in a group of children with cough as a dominant symptom were characterised by an increase in cough severity (daytime cough scores) and eosinophilic inflammation but not neutrophilic inflammation. However neither cough receptor sensitivity or cough scores related to airway IL-8, eosinophil cationic protein, myeloperoxidase or serum eosinophil cationic protein, and, asthma scores consistently related to cough score only early in the asthma exacerbation phase.

Asthma↗

Optimization of sputum-processing methods for the measurement of interleukin-5: effects of protease inhibition.

BACKGROUND: Interleukin (IL)-5 measurement in sputum samples has produced variable results that appear to be due to methodological problems. The aim of the present study was to investigate the effects of dithiothreitol (DTT), sputum protease inhibition and sample storage on IL-5 recovery in order to develop a method to accurately measure IL-5 in dispersed sputum supernatant. METHODOLOGY: Measurement of IL-5 in sputum was performed in 22 subjects with airway disease. Interleukin-5 recovery was measured in samples spiked with recombinant human IL-5 using a commercial ELISA. A mix of four protease inhibitors (PI) was added to sputum processed using the selection method with dispersion using DTT and stored with and without inhibitors. RESULTS: The addition of PI to sputum resulted in a 24% increase in IL-5 recovery. Recovery was not further increased with the addition of a blocking protein. Storage of IL-5-spiked sputum gave significantly less recovery. The addition of PI to sputum processed with DTT had no effect on total cell count, viability or cell differential. CONCLUSION: Interleukin-5 recovery is increased by the addition of PI to samples processed using the selected portion method with DTT dispersion. A protease inhibitor cocktail should be added to sputum for IL-5 assay.

Adult↗

Increased plasma fatty acid concentrations after respiratory exacerbations are associated with elevated oxidative stress in cystic fibrosis patients.

BACKGROUND: Oxidative stress and depleted antioxidant defenses occur in stable cystic fibrosis patients. During acute infection, the balance between oxidants and antioxidants may be further disturbed. OBJECTIVE: We examined the oxidative stress during acute infection in cystic fibrosis patients by measuring 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) and antioxidant defenses in relation to dietary intake, fatty acid status, immune function, and clinical status. DESIGN: Plasma concentrations of total 8-iso-PGF(2 alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid compositions; erythrocyte glutathione concentrations; glutathione peroxidase and superoxide dismutase activity; sputum glutathione and 8-iso-PGF(2 alpha) concentrations; lung function; clinical symptoms; and dietary intake were measured in 15 cystic fibrosis patients before and after 10-14 d of intravenous antibiotic treatment for a pulmonary exacerbation. RESULTS: After treatment, respiratory status improved (percentage of forced expiratory volume in 1 s: 60 +/- 6% at baseline compared with 74 +/- 7% after treatment, P = 0.01), quality of well-being improved (P = 0.001), and total plasma 8-iso-PGF(2 alpha) concentrations increased from 469 nmol/L at baseline (interquartile range: 373-554 nmol/L) to 565 nmol/L after treatment (interquartile range: 429-689 nmol/L; P = 0.008). Total energy, fat, carbohydrate, and protein intakes per kilogram body weight also increased; however, dietary antioxidant intake was unchanged. Plasma fatty acid concentrations increased after treatment, strongly correlating with plasma 8-iso-PGF(2 alpha) concentrations (r = 0.768, P = 0.001). There were no significant changes in white cell counts or plasma concentrations of vitamins E and C or beta-carotene. Erythrocyte glutathione peroxidase activity was reduced after treatment, whereas there was no significant change in superoxide dismutase activity. CONCLUSIONS: Oxidative stress increased after treatment for pulmonary exacerbations and was strongly linked to increased concentrations of plasma fatty acids. Although intravenous antibiotic therapy and physiotherapy improved lung function within 10-14 d of treatment, the biochemical effects of oxidation continued further. Thus, antioxidant intervention during treatment for and recovery from acute infection in cystic fibrosis should be considered.

Adolescent↗

Outpatient monitoring of asthma.

Monitoring asthma outcomes is an essential step to the successful implementation of national asthma guidelines. Symptoms, airflow obstruction and exacerbations can be monitored by patients with asthma and by physicians. Patients who practise self-monitoring in conjunction with use of a written action plan and regular medical review have significantly fewer hospitalizations, emergency room visits and lost time from work. Additional monitoring tools are under evaluation, and these include measures of airway responsiveness, airway inflammation, and Internet-based monitoring systems.

Asthma↗