Showing papers by "Peter G. Gibson published in 1998"

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis

Abstract: A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.

Epidemiological Association of Airway Inflammation with Asthma Symptoms and Airway Hyperresponsiveness in Childhood

Abstract: The role of airway inflammation in childhood asthma is not well defined, despite modern treatment approaches recommending potent anti-inflammatory therapy for an increasing number of children. In this study, induced sputum analysis was used to investigate the relationships among sputum inflammatory cells (eosinophils and mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline in a cohort of 170 children aged 8-14 years. Children who reported asthma symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic saline was strongly associated with higher levels of sputum eosinophils ([OR] 4. 36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils (OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65; nasal eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in asthma prevalence in boys in this age group. Airway inflammation with eosinophils and mast cells is likely to be important in the pathogenesis of asthma in childhood. Induced sputum analysis can be used to evaluate this problem and has the potential to be a useful tool for monitoring therapy.

Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children.

Abstract: We aimed to describe induced sputum cell counts in healthy nonasthmatic children, and to compare these to children with controlled and uncontrolled asthma. Following clinical assessment and spirometry, ultrasonically nebulized hypertonic saline was used to induce sputum from children with asthma (n=50) and without asthma (n=72). Sputum was dispersed and cell counts performed to yield total and differential cell counts. Specific stains were used for eosinophil and mast cell counts. All of the children with asthma were receiving inhaled and/or oral corticosteroids. Current asthma control was assessed in terms of symptoms and lung function. Children were classified as controlled on inhaled corticosteroids (no current symptoms, normal lung function n=15), current symptomatic asthma (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma than in nonasthmatic children. Children whose asthma was controlled, as well as those with symptoms, had more sputum eosinophils and epithelial cells than the nonasthmatics. Mast cells were found in the sputum of only four of the 42 children with asthma. This study demonstrates that eosinophilic airway inflammation and epithelial damage can occur in children with asthma. Airway inflammation persists even in those children who are receiving inhaled corticosteroids, have normal lung function and good symptomatic control of their disease.

Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells.

Abstract: Background: Chronic cough is a multifactorial condition, which, like asthma, can be associated with eosinophilic airway inflammation. In asthma, airway eosinophilia is believed to be mediated by cytokines such as interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these cytokines in chronic cough is unclear. Objective: The aim of this study was to examine gene expression for IL-5 and GM-CSF in chronic cough and compare the results with those found in asthma. Methods: We studied adults with asthma ( n = 12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) ( n = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS–responsive cough) ( n = 4). Bronchoalveolar lavage (BAL) was performed, and cytokine gene expression was assessed by using a semiquantitative reverse transcriptase polymerase chain reaction. Results: IL-5 mRNA was expressed by BAL cells from nine of 12 asthmatic subjects and six of nine subjects with ICS-responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS–responsive chronic cough (zero of four subjects, p p

Methotrexate as a steroid sparing agent for asthma in adults.

Abstract: Background Sustained oral corticosteroid use can lead to complications, so there is interest in identifying agents that can reduce oral steroid use in people with asthma. Methotrexate has attracted attention as a possible steroid sparing agent in patients with chronic oral steroid dependent asthma. Objectives The objective of this review was to assess the effects of adding methotrexate to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids. Search methods The Cochrane Airways Group Specialised Register and reference lists of identified articles were searched. Searches are current as of February 2006. Selection criteria Randomised trials of the addition of methotrexate compared with placebo in adult steroid dependent asthmatics. Duration of therapy needed to be at least 12 weeks. Data collection and analysis Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. Main results Ten trials involving a total of 185 people were included. Study design and quality, corticosteroid dosages and outcomes varied widely. There was a reduction in oral corticosteroid dose favouring methotrexate in parallel trials (weighted mean difference -4.1 mg per day, 95% confidence interval -6.8 to -1.3) and also in cross-over trials (weighted mean difference -2.9 mg per day, 95% confidence interval -5.9 to -0.2). There was no difference between methotrexate and placebo for forced expiratory volume in one minute (weighted mean difference 0.12 litre, 95% confidence interval -0.21 to 0.45). Hepatotoxicity was a common adverse effect with methotrexate compared to placebo (odds ratio 6.9, 95% confidence interval 3.1 to 15.5). Authors' conclusions Methotrexate may have a small steroid sparing effect in adults with asthma who are dependent on oral corticosteroids. However, the overall reduction in daily steroid use is probably not large enough to reduce steroid-induced adverse effects. This small potential to reduce the impact of steroid side-effects is probably insufficient to offset the adverse effects of methotrexate.

Promoting evidence-based alternative medicine.

Abstract: A lternative medicine is an integral part of the healthcare of many Australians. Approximately half of our population use at least one non-medically prescribed alternative medicine each year, and about 20% ofAustralians visit an alternative medicine practitioner.' The estimated annual expenditure is over $900 million.' There are probably many reasons for this widespread use of alternative medicine; one that has been suggested is a growing dissatisfaction with orthodox medicine.s That alternative medicine is of increasing relevance to orthodox medicine is illustrated by the finding that almost two-thirds of United States medical schools have courses on alternative or complementary medicine.\" Despite the demand for alternative medicine, there is a paucity of rigorous evidence about its effectiveness; there are few studies, and those that exist are often inconclusive. For instance, a meta-analysis of placebo-controlled trials of homoeopathy found \"insufficient evidence that homoeopathy is clearly efficacious for any single condition\", but, interestingly, that homoeopathy may be better than placebo for seasonal allergies and postoperative ileus .' On balance, it must also be acknowledged that there are many gaps in the evidence about the effectiveness of orthodox medicine; however, orthodox medical practitioners are increasingly committed to evidence-based practice.\" A major challenge for evidence-based orthodox medicine is the availability of high quality clinical studies to form its evidence. For alternative medicine, there is a similar, if not greater, challenge that is demonstrated in this issue of the Journal. Liu and Douglas (page 579) reviewed published reports (in English and Chinese) on the use of Chinese herbal medicines for acute respiratory infections (ARI);6 Bowler et al (page 575) studied the efficacy of Buteyko breathing techniques (BBT) in the management of asthma.' Both articles highlight the difficulties in designing and implementing clinical research for interventions outside of the double-blind randomised controlled trial (RCT) of conventional drug therapy. In the systematic review of Chinese herbal medicines for ARI by Liu and Douglas, we learn of 27 studies that evaluated these products using RCT or controlled clinical trial methods.\" Although it is clear that scientists are trying to establish the efficacy of alt ernative therapies using widely accepted methods, the quality of the studies was insufficiently rigorous to allow conclusions to be drawn about the efficacy of herbal medicines. Specific problems with the reports included inadequate information about randomisation, and doubts about the quality of outcome data and statistical analysis. Liu and Douglas did identify one preparation, Shuang Huang Lian, as a promising remedy worthy of further study. The reviewers identify approaches

Use of induced sputum to examine airway inflammation in childhood asthma

Abstract: Airway inflammation is important in the pathogenesis of asthma, during which it may lead to symptomatic exacerbations and increases in asthma severity, as well as contribute to future decline in asthma status. The use of induced sputum has emerged as an important and useful technique to study airway inflammation. It has particular advantages in the study of childhood asthma because it is noninvasive and allows samples to be collected on repeated occasions in children over 7 years of age. The results of cell counts are reliable when the sputum is processed in a standardized manner involving selection from saliva, cell dispersion, and quantitative cytology. Children with asthma have increased eosinophils and mast cells, which may persist even with high doses of inhaled corticosteroid therapy. During a severe exacerbation of asthma, there is an intense and heterogeneous inflammatory response involving eosinophil and neutrophil accumulation and activation. Characterization of the relevance of airway inflammation in children with asthma is important. (J Allergy Clin Immunol 1998;102:S100-1.)

Severe exacerbation of chronic obstructive airways disease: health resource use in general practice and hospital.

Abstract: The objective of this study is to examine the treatment of exacerbations of chronic obstructive airways disease (COAD) in the hospital and in the community setting using a retrospective study of patients admitted to a major teaching hospital combined with a general practice chart audit. The admission records for 248 admissions from 128 patients were reviewed. Most patients (70%) had visited their GP within 2 weeks of admission, antibiotics were prescribed for 30% of the exacerbations while 51% were treated with ingested corticosteroids. During hospitalization, features of infection were present in 64% (n = 159) of exacerbations and 79% (n = 196) received antibiotics. Patients were also treated with nebulized bronchodilators, oxygen and corticosteroids (82%). The median length of stay was 10 days (range 0-55). There was a high readmission rate (70%) at 1 year for exacerbation of COAD during the study period. Exacerbations of COAD frequently demonstrated the clinical features of infection. Treatment in general practice was less intensive than in hospital, and there is a need to reconcile these differences with studies of early therapy with antibiotics and corticosteroids. Although corticosteroids were used less often in general practice, the literature in this area is not conclusive and the evidence supporting guideline recommendations is not explicit. There are opportunities to examine the role of early therapy and early discharge programmes to minimize the cost burden from exacerbations of COAD.

Airway inflammation after treatment with aerosolized deoxyribonuclease in cystic fibrosis.

Abstract: Recombinant human deoxyribonuclease (rhDNase) has been shown to reduce sputum viscoelasticity and to improve lung function in patients with cystic fibrosis (CF). The aim of this study was to determine whether airway inflammation would decrease after administration of rhDNase. Twenty patients with CF and chronic suppurative lung disease inhaled 2.5 mg of rhDNase daily for 1 month. Before and after the 1-month trial, lung function was measured and sputum was obtained, either after spontaneous expectoration or after sputum induction with hypertonic saline. Sputum total cell and differential counts were measured using techniques previously described. The mean age of the patients was 16.8 years (range, 6.7–27.5). After 1 month of rhDNase, mean FEV1 increased from a baseline of 62.3% predicted to 70.8% (P = 0.02, paired t test); and FVC increased from 74.4% to 83.9% predicted (P = 0.007). No significant differences were found in sputum cytology before or after rhDNase (median total cell counts 16.0 × 106/ml vs. 19.3 × 106/ml, P = 0.68). Thirteen patients had a 10% or greater increase in FEV1 after rhDNase (responders). Initial lung function was less in responders than in nonresponders (53.5% vs. 78.6%, P = 0.007). There was no significant change in total cell count and neutrophil count after rhDNase in either responders or nonresponders. We conclude that airway inflammation, as measured by total cell counts in sputum, was a prominent feature in cystic fibrosis, and neutrophils were the dominant inflammatory cells. Although the administration of rhDNase resulted in significant improvements in FEV1, there was no evidence of accompanying changes in airway inflammation. Pediatr Pulmonol. 1998;26:97–100. © 1998 Wiley-Liss, Inc.

Peer-led asthma education for adolescents: development and formative evaluation

Abstract: Issue addressed: Asthma is a major health problem among adolescents. Prior studies have identified substantial morbidity from asthma and a generally poor understanding of asthma among adolescents. There is a need to develop educational interventions to address these issues. Methods: We developed a multi-component intervention model where students are involved in both teaching and learning about asthma. The model is based on recognised health promotion theories and consultation with the school community. We trained 14 student volunteers from Year 11 as Asthma Peer Leaders in three 90-minute workshops, who then instructed Year 10 students about asthma in three 45-minute lessons. Students from each Year 10 class then presented a three- to five-minute asthma performance to the Year 7 students, staff and invited guests. To assess the process, quality and feasibility of the program, asthma peer leaders, target student groups (Years 10 and 7) and key staff members of the school completed semi-structured questionnaires. Results: Asthma peer leaders reported that the training workshops were interesting and the educational component of the program enhanced their knowledge and confidence about asthma. They found the teaching resources easy to use. Year 10 students reported that student-to-student teaching and student asthma performances were the highlights of the program. Feedback from Year 7 students included increased awareness about asthma, its management and avoidance of smoking. Overall the program was well accepted by the school community with full student participation. A key factor, was the students' enthusiasm and motivation to participate. The students felt personally involved because they could direct the action based on their own initiative. School staff supported the integration of the program in the school's health curriculum for future years. Conclusion: We have demonstrated that peer teaching is a useful and feasible health promotion strategy to disseminate asthma information among high school students. So what? This study indicates that a collaborative approach to asthma health promotion will enable its adoption and successful implementation in a school setting. (author abstract)

Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness.

Abstract: Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.

How to measure airway inflammation: induced sputum

Abstract: Induced sputum examination has emerged as an important investigative tool in airway diseases. Sputum can be easily induced by ultrasonic nebulization of hypertonic saline. Inprovements in sputum processing have established that sputum provides reproducible measurements of cell counts and fluid phase mediators. Adults and children with stable asthma demonstrate an infiltrate of eosinophils. With an exacerbation of asthma the eosinophil infiltrate increases and the cells become activated in response to cytokines including interleukin-5. A neutrophil infiltrate may accompany some exacerbations. Exacerbations resolve under the influence of corticosteroid therapy. Eosinophils undergo apoptosis and are removed by macrophages. Eosinophilic bronchitis is an important component in up to 20% of patients with chronic cough. Sputum examination promises to be an important technique to facilitate the understanding and management of asthma and cough in adults and children.