Lack of efficacy of a herbal preparation (RCM-102) for seasonal allergic rhinitis: a double blind, randomised, placebo-controlled trial.

BACKGROUND: A herbal preparation, known as RMIT Chinese Medicine 102 (RCM-102) consisting of eight herbs which demonstrates inhibition of the release of key inflammatory mediators associated with seasonal allergic rhinitis (SAR) was used. This study evaluated the efficacy and safety of RCM-102 for SAR. OBJECTIVE: This study evaluated the efficacy and safety of RCM-102 for SAR. METHODS: This randomised placebo-controlled trial involved subjects aged between 18 and 65 who were randomly assigned to either RCM-102 or a placebo group. After a two-week baseline period, all subjects took either RCM-102 or placebo capsules (two capsules each time, three times daily with a four hour interval) for a period of eight weeks. The primary end-points were the Five-Point Scale symptom scores. Rhinoconjunctivitis Quality of Life Questionnaire, relief medication usage, adverse events, kidney and liver function tests and full blood examination were secondary end-points. Intention-to-treat analysis was applied. RESULTS: One hundred and four subjects were randomised with 52 in each group. Ninety-five subjects (47 and 48 subjects in RCM-102 and placebo groups) completed the trial. Nine subjects withdrew from the study prior to the end of the second treatment week. At the end of the trial, there were no significant differences between the two groups with respect to all outcome measures. There were no liver or kidney function abnormalities reported. CONCLUSION: This mechanism-based RCM-102 was safe but not more beneficial than placebo for patients with SAR.

Associations between fatty acids in colostrum and breast milk and risk of allergic disease.

BACKGROUND: Exposure to n-3 polyunsaturated fatty acids (PUFA) in early life is hypothesized to offer protection against atopic disease. However, there is controversy in this area, and we have previously observed that high levels of n-3 fatty acid (FA) in colostrum are associated with increased risk of allergic sensitization. OBJECTIVE: The aim of the study was to assess the relationship between FA profile in breast milk and risk of childhood atopic disease. METHODS: A high-risk birth cohort was recruited, and a total of 224 mothers provided a sample of colostrum (n=194) and/or 3-month expressed breast milk (n=118). FA concentrations were determined by gas chromatography. Presence of eczema, asthma and rhinitis were prospectively documented up to 7 years of age. RESULTS: High levels of n-3 22:5 FA (docosapentaenoic acid, DPA) in colostrum were associated with increased risk of infantile atopic eczema [odds ratio (OR)=1.66 per 1 standard deviation increase, 95% confidence interval (CI)=1.11-2.48], while total n-3 concentration in breast milk was associated with increased risk of non-atopic eczema (OR=1.60, 95% CI=1.03-2.50). Higher levels of total n-6 FA in colostrum were associated with increased risk of childhood rhinitis (OR=1.59, 95% CI=1.12-2.25). There was no evidence of associations between FA profile and risk of asthma. CONCLUSION: In this cohort of high-risk children, a number of modest associations were observed between FA concentrations in colostrum and breast milk and allergic disease outcomes. Further research in this area with larger sample sizes is needed.

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.

Changes in indoor allergen and fungal levels predict changes in asthma activity among young adults.

BACKGROUND: Exposures to allergens are thought to be important risk factors for asthma. We conducted a longitudinal study of indoor allergen and fungal levels in Melbourne homes between 1996 and 1998 to examine the effect of changes in allergen exposure upon asthma and associated outcomes. METHODS: Participants were visited at home in 1996 (n=485) and 1998 (n=360), when dust and air samples were collected from their bedrooms and assayed for Der p 1, Fel d 1, ergosterol and fungal propagules. Subjects then attended the lung function laboratory to complete a questionnaire, spirometry, methacholine challenge and skin prick testing. The associations between the change in allergen levels and change in clinical outcomes were examined using multiple logistic and linear regression. RESULTS: Participants whose Cladosporium fungal exposure doubled had 52% greater odds of having had an attack of asthma in the last 12 months. A doubling of fungal exposure was also associated with 53% greater odds of developing atopy. A doubling of Fel d 1 floor levels was associated with 73% increased odds of doctor-diagnosed asthma. A doubling of Der p 1 levels in bed dust was associated with a 64% greater odds of persistent bronchial hyper-reactivity. CONCLUSIONS: These findings provide evidence that changes in indoor levels of fungi and house dust mites can affect the risk of development and persistence of asthma and atopy in adults. Further studies are required to establish any benefit of sustained reductions in indoor allergen exposures, and to determine whether these effects are truly 'allergic' or because of immune stimulation in the airway through other less specific mechanisms.

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.

Fatty acid levels and risk of asthma in young adults.

BACKGROUND: There is current interest in the possible protective effect of long chain (n-3) fatty acids from fish in chronic lung diseases such as asthma. The aim of this community based cross sectional study was to determine whether plasma long chain (n-3) fatty acids, as a measure of dietary intake, differed between 1601 young adults with and without asthma. METHODS: Subjects of mean (SD) age 34.6 (7.1) years completed a detailed respiratory questionnaire, food frequency questionnaire, skin prick testing, and lung function tests including methacholine challenge test for bronchial hyperreactivity (BHR) and had venous blood taken for analysis of plasma fatty acids. Plasma fatty acid levels (%) were analysed using multiple logistic regression with alternative definitions of asthma and atopy as the outcomes. RESULTS: Atopy was not associated with any plasma fatty acid. The n-3 polyunsaturated fatty acids and n-6:n-3 ratio were not consistently associated with asthma or atopy. The n-6 polyunsaturated fatty acid dihomo gamma-linolenic acid (DHGLA) was positively associated with current asthma (OR=1.30, 95% CI 1.06 to 1.60), asthma (OR=1.34, 95% CI 1.13 to 1.60), and doctor diagnosed asthma (OR=1.25, 95% CI 1.06 to 1.48). CONCLUSION: Plasma n-3 fatty acids are not associated with a reduced risk of asthma or atopy among young adults. The association of DHGLA with asthma warrants further research to determine a cause-effect relationship.

Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants.

BACKGROUND: Australia has one of the highest prevalence rates internationally of allergic conditions, such as asthma and eczema. Atopy is one hallmark for the development of allergic disease and predisposes to allergic inflammation in the target organs. omega-3 (n-3) fatty acids (FAs) are thought to act as precursors to the formation of less active inflammatory mediators, with the potential to reduce inflammation. OBJECTIVE: To investigate whether increased n-3 FA levels in maternal breast milk are associated with a lower risk of developing atopy in infancy. METHODS: Subjects were part of the prospective Melbourne atopy cohort study, which involved 620 children born into families where at least one first-degree relative had an atopic disease. Some 224 women (mean age 31.4+/-4.2 (SD) years, with 73.2% (n=164) having self-reported atopy) provided either a colostrum (n=194) or 3-month expressed breast milk (EBM) sample (n=118). Maternal colostrum and 3-month EBM samples were analysed for FA content by gas chromatography. Skin prick tests (SPTs) to six common allergens were performed on infants at 6, 12 and 24 months of age and on mothers who agreed at study entry. RESULTS: For infants sensitized to foods at 6 months (n=29), the total n-3 FA level in the colostrum was significantly higher (P=0.004) as were levels of individual long-chain n-3 FAs, docosoapentaenoic acid (DPA, C22:5, P=0.001) and docosahexaenoic acid (DHA, C22:6, P=0.002) than in non-sensitized infants. Infants with aero-allergen sensitization at 24 months (n=30) had higher levels of the n-3 FA, DPA (P=0.002) and DHA (P=0.007), and similarly higher total n-3 FA (P=0.009) in maternal colostrum than those infants who were not sensitized. CONCLUSION: Higher n-3 FA levels in the colostrum do not appear to confer protection against, but may be a risk factor for, the eventual development of atopy in high-risk breastfed infants.

Asthma and vaccination history in a young adult cohort.

BACKGROUND: It has been suggested that childhood vaccinations may be associated with the onset of asthma. We investigated the association between asthma, atopy and vaccination history in a cohort of young adults living in Melbourne, Australia. METHODS: Subjects were aged between 22 and 44 years and were surveyed by an interviewer-administered questionnaire. Questions were asked about vaccinations to measles, mumps and rubella (MMR), triple antigen (DTP), hepatitis B and Sabin polio vaccine (OPV). Atopy was assessed by skin prick testing to common aeroallergens. RESULTS: There was no significant association observed for subjects diagnosed with asthma who had received measles or MMR vaccinations compared with those who did not receive measles or MMR vaccinations (RR 1.33, 95% CI 0.98-1.80). Non-significant associations were also observed for OPV and hepatitis B vaccinations (RR 3.27, 95% CI 0.50-21.3 and RR 1.08, 95% CI 0.83-1.41, respectively). However, subjects reporting full immunisation were found to be at higher risk to asthma (RR 1.52, 95% CI 1.09-2.11) but not atopy. CONCLUSIONS: Our results show relatively weak support for the hypothesis that childhood vaccinations may lead to increased risk of asthma, but caution is advised due to possible recall bias.

Effect of adding a Chinese herbal preparation to acupuncture for seasonal allergic rhinitis: randomised double-blind controlled trial.

OBJECTIVE: To assess whether the addition of a Chinese herbal medicine formula to acupuncture affects the severity of symptoms and quality-of-life scores among patients with seasonal allergic rhinitis. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: University teaching and research clinic, Australia. PARTICIPANTS: Sixty-five patients with seasonal allergic rhinitis, who were recruited through public media. INTERVENTION: Between July and December 1999, patients received acupuncture twice a week for 8 weeks plus either a Chinese herbal drug formula (n=33) or placebo (n=32) at a dosage of four capsules, three times daily. MAIN OUTCOME MEASURES: The severity of nasal and non-nasal symptoms on a five-point scale, as assessed by both patients and an ear, nose, and throat specialist, and quality-of-life scores as measured by the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire. RESULTS: Sixty-one patients completed the study (31 in the intervention group and 30 in the control group). After 8 weeks, no significant difference was found between the two groups in the severity of nasal and non-nasal symptoms and in the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire scores. Intention-to-treat analysis of categorical variables showed moderate-to-marked improvement rates of 72.7% and 81.2% for intervention and control groups, respectively. Six patients reported mild adverse events-three from each of the study groups. CONCLUSION: The Chinese herbal formulation under investigation did not provide additional symptomatic relief or improvement in quality-of-life scores among patients with seasonal allergic rhinitis who were receiving acupuncture.

Residential characteristics predict changes in Der p 1, Fel d 1 and ergosterol but not fungi over time.

BACKGROUND: Allergen and fungal exposures are important risk factors for asthma. We conducted a longitudinal analysis of allergen levels in Melbourne homes between 1996 and 1998 to examine the effects of changing residential characteristics on allergen and fungal levels. We also examined the changes in levels of indoor allergens. METHODS: The subjects were participants in the European Community Respiratory Health Survey (ECRHS) in Melbourne. In 1996, 485 subjects participated in a follow-up study, which involved both home and laboratory visits. Dust and air samples were collected from participants' bedrooms and a validated residential questionnaire was administered. In 1998, 360 participants underwent further follow-up. House dust mite (Der p 1) and cat allergens (Fel d 1) and ergosterol were measured in dust. RESULTS: We observed moderate within home correlations between 1996 and 1998 in floor Der p 1 (intraclass correlation ICC=0.48), bed Der p 1 (ICC=0.61), Fel d 1 (kappa=0.53) and ergosterol (ICC=0.28) levels. We found that the floor Der p 1 levels decreased from 1996 to 1998 in the homes of participants who moved to an attached home, moved their bedrooms to the first floor, removed fitted carpet or central heating. Replacing or vacuuming the mattress more than twice per year reduced levels of Der p 1 in the bed. Ergosterol levels were reduced by removing visible mould and fitted carpet. CONCLUSIONS: These findings provide evidence to support current advice with regard to allergen avoidance in patients with dust mite and fungal allergies.

Role of intravenous immunoglobulin in severe steroid-dependent asthma.

BACKGROUND: Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma. AIMS: To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. METHOD: Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. RESULTS: There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. CONCLUSION: IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.

Reported adverse food reactions overestimate true food allergy in the community.

OBJECTIVE: To determine the extent to which perceived adverse food reactions were associated with IgE mediated food allergy, as defined by skin prick testing (SPT). DESIGN: A cohort epidemiological study. Participants underwent SPT to five common food allergens (cow's milk, peanut mix, egg white, shrimp and whole grain wheat mix) and were asked whether they had ever suffered any food 'illness/trouble', and if so to list such food(s). A positive SPT was defined as wheal diameter of > or =3 mm. Cohen's kappa (kappa) was used to assess the agreement between SPT and self-reported reactions to food(s) which contained the allergen of interest. SETTING: Randomly selected adults who took part in the follow-up of the European Community Respiratory Health Survey (ECRHS) in 1998. SUBJECTS: The subjects were 457 adults aged 26-50 y. RESULTS: Fifty-eight (13%) adults were sensitised to at least one food allergen whilst 99 adults (22%) reported illness to food(s) nearly always. However, only seven subjects who reported illness to a food also had a positive SPT to the same food. The prevalence of adverse food reactions associated with IgE mediated allergy in the adult general population would be less than 1.5% (7/457). The agreement between SPT and self-reported illness to food(s) was poor for cow's milk (kappa=0) and wheat (kappa=0), slight for shrimp (kappa=0.16) and egg white (kappa=0.09) and fair for peanut mix (kappa=0.37). CONCLUSIONS: There was little agreement between self-reported perceived illness to food(s) known to contain the food allergen of interest, and positive SPT, suggesting that most reactions are not due to IgE mediated food allergy.