Showing papers by "Peter G. Gibson published in 2004"

Written action plans for asthma: an evidence-based review of the key components

Abstract: Background: Written action plans for asthma facilitate the early detection and treatment of an asthma exacerbation. Several versions of action plans have been published but the key components have not been determined. A study was undertaken to determine the impact of individual components of written action plans on asthma health outcomes. Methods: Randomised controlled trials (n = 26) that evaluated asthma action plans as part of asthma self-management education were identified. Action plans were classified as being individualised and complete if they specified when and how to increase treatment (n = 17), and as incomplete (n = 4) or non-specific (n = 5) if they did not include these instructions. Results: For individualised complete written action plans the use of 2–4 action points and the use of both inhaled (ICS) and oral (OCS) corticosteroid consistently improved asthma outcomes. Action points based on personal best peak expiratory flow (PEF) consistently improved health outcomes while those based on percentage predicted PEF did not. The efficacy of incomplete action plans was inconclusive because of insufficient data. Non-specific action plans led to improvements in knowledge and symptoms. Conclusion: Individualised written action plans based on personal best PEF, using 2–4 action points, and recommending both ICS and OCS for treatment of exacerbations consistently improve asthma health outcomes. Other variations appear less beneficial or require further study. These observations provide a guide to the types of variations possible with written action plans, and strongly support the use of individualised complete written action plans.

Azoles for allergic bronchopulmonary aspergillosis associated with asthma

Abstract: BACKGROUND Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWERS' CONCLUSIONS Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.

Anticholinergic agents for chronic asthma in adults

Abstract: BACKGROUND Anticholinergic agents such as ipratropium bromide are sometimes used in the treatment of chronic asthma. They effect bronchodilation and have also been used in combination with beta2-agonists in the management of chronic asthma. OBJECTIVES To examine the effectiveness of anticholinergic agents versus placebo and in comparison with beta2-agonists or as adjunctive therapy to beta2-agonists. SEARCH STRATEGY The Cochrane Airways Group asthma and wheeze database was searched with a pre-defined search strategy. Searches were current as of August 2003. Reference lists of articles were also examined. SELECTION CRITERIA Randomised trials or quasi-randomised trials were considered for inclusion. Studies assessing an anticholinergic agent versus placebo or in combination/comparison with beta2-agonists were included. In practice, all beta2-agonists were short acting. Short-term (less than 24 hours duration) and longer-term studies were separated; the latter are reported in this review and the former in the review, "Anticholinergic agents for chronic asthma in adults short term". DATA COLLECTION AND ANALYSIS Two reviewers independently assessed abstracts for retrieval of full text articles. Papers were then assessed for suitability for inclusion in the review. Data from included studies were extracted by two reviewers and entered into the software package (RevMan 4.2). We contacted authors for missing data and some responded. Adverse effect data were analysed if reported in the included studies. MAIN RESULTS The studies analysed were in two groups: those comparing anticholinergics with placebo and those comparing the combination of anticholinergics with short acting beta2-agonists versus short acting beta2-agonists alone. The former group had 13 studies involving 205 participants included in this review, and the latter 9 studies involving 440 patients. Generally methodological quality was poorly reported, and there were some reservations with respect to the quality of the studies. Despite the limited number of studies that could be combined, anticholinergic agents in comparison with placebo resulted in more favourable symptom scores particularly in respect of daytime dyspnoea (WMD -0.09 (95%CI -0.14, -0.04, 3 studies, 59 patients). Daily peak flow measurements also showed a statistically significant improvement for the anticholinergic (e.g. morning PEF: WMD =14.38 litres/min (95%CI 7.69, 21.08; 3 studies, 59 patients). However the clinical significance is small and in terms of peak flow measurements equates to approximately a 7% increase over placebo. The more clinically relevant comparison of a combination of anticholinergic plus short acting beta2-agonist versus short acting beta2-agonist alone gave no evidence in respect of symptom scores or peak flow rates of any significant differences between the two regimes. Again there are reservations with respect to the quality of the information from which these conclusions are drawn. REVIEWERS' CONCLUSIONS Overall this review provides no justification for routinely introducing anticholinergics as part of add-on treatment for patients whose asthma is not well controlled on standard therapies. This does not exclude the possibility that there may be a sub-group of patients who derive some benefit and a trial of treatment in individual patients may still be justified. The role of long term anticholinergics such as tiotropium bromide has yet to be established in patients with asthma and any future trials might draw on the messages derived from this review.

Mechanisms of asthma and allergic inflammation Rostrum Can bacterial endotoxin exposure reverse atopy and atopic disease

Abstract: Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to downregulate pre-existing airway eosinophilia and hyperreactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema. (JAllergyClin Immunol 2004;114:1051-4.)

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

Abstract: 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.

Can bacterial endotoxin exposure reverse atopy and atopic disease

Abstract: Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to downregulate pre-existing airway eosinophilia and hyperreactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema.

The effectiveness of intranasal corticosteroids in combined allergic rhinitis and asthma syndrome

Abstract: Summary Background Allergic rhinitis (AR) and asthma often coexist and may represent two manifestations of the same disease recently named combined AR and asthma syndrome (CARAS). Aim To review the common pathophysiology of combined AR and asthma and to investigate the efficacy of intranasal corticosteroids (INCS). Methods Medline was used to identify articles relevant to mechanisms. A Cochrane systematic review was performed to assess the efficacy of INCS in CARAS. Results There is cross-talk, evidence of a common inflammatory response in both sites, linked by a systemic component. The efficacy of anti-inflammatory INCS on asthma outcomes was assessed in a systematic review of 12 randomized controlled trials involving 425 subjects. After INCS there were non-significant trends for improvement in asthma symptom score (standardized mean difference (SMD) of 0.61; P=0.07), forced expiratory volume in 1 s (SMD of 0.31; P=0.08), and morning peak expiratory flow (weighted mean difference of 36.51; P=0.06). There was no impact on methacholine airways responsiveness (SMD of −0.20; P=0.4). The review identified two promising new treatment options in united airway disease such as INCS as monotherapy in rhinitis and mild asthma, and a combined intranasal and intrabronchial corticosteroid (IBCS) deposition technique. Conclusion Common mucosal inflammatory responses occur in CARAS. This systematic review shows trends for a benefit of INCS in CARAS, but recognizes that more research is needed. At this stage, the current best practice is to treat asthma conventionally with IBCS with or without β2-agonist and to add INCS to improve specific rhinitis symptoms.

Initial starting dose of inhaled corticosteroids in adults with asthma: a systematic review

Abstract: Background: Asthma guidelines vary in their recommendations for the initial dose of inhaled corticosteroid (ICS) in asthma A systematic review of the literature was conducted to establish the optimal starting dose of ICS for asthma in adults Methods: Randomised controlled trials comparing two doses of the same ICS in adults with asthma and no concomitant inhaled or oral corticosteroid were assessed Included trials were analysed according to the following ICS dose comparisons: high (⩾800 μg/day beclomethasone (BDP)) versus moderate (400<800 μg/day BDP) (n = 7); moderate versus low (<400 μg/day BDP) (n = 6); step down versus constant dose (n = 4) Results: Fourteen publications describing 13 trials were included in the review Studies (n = 4) that compared a step down approach with a constant moderate/low dose of ICS found no difference in lung function, symptoms, or rescue medications between the two treatment approaches (p>005) There was no difference in the change in morning peak flow after treatment with high compared with moderate dose ICS When compared with low dose ICS, moderate dose ICS significantly improved morning peak flow (change from baseline WMD 1114 l/min, 95% CI 134 to 2093) and nocturnal symptoms (SMD −029, 95% CI −053 to −006) Conclusions: For patients with asthma who require ICS, starting with a moderate dose is equivalent to starting with a high dose and stepping down The small non-significant benefits of starting with a high ICS dose are not of sufficient clinical benefit to warrant its use Initial moderate ICS doses appear to be more effective than an initial low ICS dose

Effect of saliva contamination on induced sputum cell counts, IL‐8 and eosinophil cationic protein levels

Abstract: Excessive salivary contamination of induced sputum samples prevents the satisfactory examination of lower airway inflammation. The effects of salivary contamination on different sputum fluid phase measures and the levels of salivary contamination preventing analysis are not defined. The present study sought to examine this by investigating the effect of increasing salivary contamination on induced sputum samples. Sputum and saliva samples from subjects with asthma and healthy controls were collected, and treated with dithiothreitol (DTT). Saliva was then added to aliquots of dispersed sputum in increasing proportions (0% to 100%). The effect of increasing saliva contamination was assessed on sputum total cell count, viability, differential cell count and fluid phase levels of interleukin (IL)-8, eosinophil cationic protein (ECP) and total protein. The addition of saliva to induced sputum reduced total cell counts and absolute cell counts but did not change the differential cell count. Levels of fluid phase ECP and IL-8 were significantly reduced with increased salivary contamination. There was a progressive reduction in ECP and IL-8, which reached significance at 70% and 80% saliva contamination, respectively. IL-8 levels corrected for total protein showed no change with increasing saliva concentrations. Induced sputum differential cell counts expressed as the proportion of nonsquamous cells are robust measures that are not influenced by salivary contamination. Studies reporting total and absolute cell counts and fluid phase mediator levels require control for squamous contamination.

Genetic background affects susceptibility in nonfatal pneumococcal bronchopneumonia

Abstract: A nonfatal pneumococcal lung infection model was required to investigate immune responses during recovery, and the interaction of other diseases subsequent to infection. A murine model of nonfatal pneumococcal lung infection was developed and the effect of genetic background on susceptibility was determined in BALB/c and C57BL/6 mice. Bacteria colonised the lungs and mice developed mild clinical illness with pathophysiology similar to human bronchopneumonia. Recovery was associated with immune cell influx, which cleared bacteria but induced tissue damage characteristic of pneumococcal bronchopneumonia. After clearance, immune cell populations returned to normal and tissues appeared less inflamed. Although bacterial exposure and clearance were similar, the extent of immune cell influx and tissue damage differed significantly. Larger numbers of neutrophils and lymphocytes entered lung tissue and the affected area was greater in BALB/c compared with C57BL/6 mice. An inflammatory basis for differences was determined with greater levels of phagocytosis and oxidative burst observed in BALB/c mice. C57BL/6 mice cleared the low inoculum with a reduced immune response; however, C57BL/6 mice are more susceptible to larger inocula, which overwhelms the immune system. These different susceptibilities result from a greater inflammatory response in BALB/c compared with C57BL/6 mice. This work was funded by a Clive & Vera Ramaciotti Research Foundation Grant, the Respiratory SP&T funds, John Hunter Hospital, and the Hunter Medical Research Institute, Newcastle, Australia.

The European Network for Understanding Mechanisms Of Severe Asthma Study.

Abstract: To the Editor: We found the results of the European Network For Understanding Mechanisms Of Severe Asthma (ENFUMOSA) study 1 and its accompanying Editorial 2 very interesting and would like to raise two issues, one regarding classification of subjects, and the other concerning pathogenesis. The ENFUMOSA study defined a group with severe asthma, requiring high­dose inhaled corticosteroids who continued to experience severe exacerbations of asthma. These subjects differed from the comparison group by having less atopy and increased sputum neutrophils. It was hypothesised that other environmental factors, such as infections, may be important. We recently reviewed the inflammatory …

Smokers and ex-smokers with chronic stable asthma did not respond to high dose oral corticosteroids

Abstract: Chaudhuri R, Livingston E, McMahon AD, et al . Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med 2003;168:1308–11. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Q In patients with chronic stable asthma, is bronchodilator and symptomatic response to high dose oral corticosteroids affected by smoking status? Clinical impact ratings GP/FP/Primary care ★★★★★☆☆ IM/Ambulatory care ★★★★★☆☆ Respirology ★★★★★★☆ ### ![Graphic][5] Design: randomised, placebo controlled, crossover study. ### ![Graphic][6] Allocation: concealed.* ### ![Graphic][7] Blinding: blinded {patients, clinicians, data collectors, outcome assessors, and data analysts}†.* ### ![Graphic][8] Follow up period: 2 weeks. ### ![Graphic][9] Setting: hospital clinics in Glasgow, UK ### ![Graphic][10] Patients: 59 patients who were 18–55 years of age (mean age 42 y, 72% men; based on 50 patients), had chronic asthma, forced expiratory volume in 1 second (FEV1) of 50–85% predicted, and ⩾15% reversibility of FEV1 after nebulised albuterol (2.5 mg). Exclusion criteria: asthma exacerbation, use of oral … [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BRespir%2BCrit%2BCare%2BMed%26rft_id%253Dinfo%253Adoi%252F10.1164%252Frccm.200304-503OC%26rft_id%253Dinfo%253Apmid%252F12893649%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1164/rccm.200304-503OC&link_type=DOI [3]: /lookup/external-ref?access_num=12893649&link_type=MED&atom=%2Febmed%2F9%2F4%2F115.atom [4]: /lookup/external-ref?access_num=000186804300012&link_type=ISI [5]: /embed/inline-graphic-1.gif [6]: /embed/inline-graphic-2.gif [7]: /embed/inline-graphic-3.gif [8]: /embed/inline-graphic-4.gif [9]: /embed/inline-graphic-5.gif [10]: /embed/inline-graphic-6.gif