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A dose-response relation of inhaled Flixotide (fluticasone propionate) in adolescents and adults with asthma: a mata-analysis
Shaun Holt et al. Wellington Asthma Research Group, Wellington, New Zealand.
Objective: To examine the dose-response relation of inhale flixotide in adolescents and adults with asthma.
Design: Meta-analysis of placebo-controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of flixotide.
Setting: Medline, Embase, and GlaxoWellcome's internal clinical study registers.
Main outcome measures: FEV1, morning and evening peak expiratory flow, night awakenings, Beta-agonist use, and major exacerbations.
Results: Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500mg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 mg/day and peaked by 500 mg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit of 100mg/day was achieved at doses of 70-170 mg/day and 90% by 100-250 mg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses around 500 mg/day. The odds ratio for patients remaining in the study at a dose of 200 mg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV1 for an inhaled dose of 200 mg/day against higher doses showed a difference in FEV1 of 0.13 of a standard deviation (0.02 to 0.29).
Conclusion: In adolescents and adult patient with asthma, most of the therapeutic benefit of inhaled flixotide is achieved with a total daily dose of 100-250 mg/day, and the maximum effect is achieved with a dose of around 500 mg/day. However these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 mg/day.
Reference: BMJ 2001; 323:253 (4 August)
Comments: Since the introduction of inhaled steroids beclomethasone in the early 1960s, doses prescribed to patients have progressively increased. Current guidelines recommend up to 2000 mg/day. This study shows that anything above 500mg/day is probably risking side effects without any added benefit.
This study also partially explains why adding a long acting Beta-agonist, like serevent (salmeterol) to inhaled steroids is more efficacious than increasing the dose of inhaled steroids beyond this dose range.
Chickpea: a major food allergen in the Indian subcontinent and its clinical and immunochemical correlation.
Sangita P. Patil, PhD; Pramod V. Niphadkar, MD; and Mrinal M. Bapat, PhD
Background: The food allergy pattern of a country is influenced by the foods most commonly consumed. In India, the majority of the population consumes a vegetarian diet made up of pulse (legumes), cereals, and vegetables. In contrast to many western countries, chickpea preparations are consumed in large quantities in India. This study reports for the first time chickpea hypersensitivity reactions diagnosed with in vivo and in vitro tests.
Methods: 1400 patients visiting allergy clinics were randomly selected for the study. Those patients reporting an allergic reaction on every occasion after eating chickpea were considered history-positive. Modified prick tests were performed with chickpea and other members of the legume family on all these patients. The claims of the history-positive patients were verified with double-blind, placebo-controlled food challenges (DBPCFCs). Proteins in chickpea extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred on nitrocellulose paper. Serum specimens from history-positive were analysed by imunoblot and ELISA. To verify the IgE specificity, an immunoblot inhibition assay was also performed.
Results: Of the 1,400 patients screened, 142 patients were history positive to some food and 59 of these implicated chickpeas. 41 patients were skin test -positive and 31 were DBPCFC-positive for chickpea. The predominant symptoms after chickpea ingestion were respiratory. The ELISA results did not correlate well with the DBPCFC results; however, the skin test results correlated with DBPCFC in 75% of patients. Immunoblot analysis showed that 70, 64, 35, and 26 kD proteins were major allergens.
Conclusion: Chickpea is an important source of allergen that can cause IgE-mediated hypersensitivity reactions ranging from rhinitis to anaphylaxis.
Reference: Annals of Allergy, Asthma & Immunology 2001; 87: 140-145.
Natural course of physical and chronic urticaria and angioedema in 220 patients.
Martina M. A. Kozel, MD, Jan R. Mekkes, MD, et al, Amsterdam, The Netherlands.
Background: Information about spontaneous remission of chronic urticaria is limited.
Objective: To investigate the natural course of urticaria, they followed up 220 adults in a prospective study.
Methods: Patients were followed up for 1 to 3 years to evaluate interventions, to detect latent causes, and to study the natural course of urticaria. The diagnosis was made by detailed history taking as well as laboratory provocation tests.
Results: 35% of all patients were free of symptoms after 1 year. In 28.9% of patients, symptoms had decreased. Spontaneous remission occurred in 47.4% of the patients in whom no cause of the urticaria and/or angioedema could be identified and in only 16.4% of the patients with physical urticaria. A cause could be identified in 53.1% of the patients. 36% of the patients had idiopathic urticaria. Chronic idiopathic urticaria combined with physical urticaria occurred in 10.9%.
Conclusion: In general, the prognosis for spontaneous remission is reasonable, with the exception of the subgroup (33.2%) with physical urticaria.
Reference: J Am Acad Dermatol 2001; 45:386-91
Comments: This study from the Department of Dermatology, University of Amsterdam, is the first study that I have seen from a Dermatology Unit, that has identified a cause for chronic urticaria in more than 50% of cases. It has been the feeling of several Allergists, including myself that the figures quoted for idiopathic chronic urticaria of 60-90% is too high. This article reminds us that when investigating patients with chronic urticaria, the more thorough the diagnostic methods, the lower the number of idiopathic cases. Also, even if a specific cause is not found, a clinically useful trigger for the chronic urticaria can be identified.
Food-Dependent Exercise-induced Anaphylaxis (FDEIAn): Clinical and laboratory Findings in 54 subjects.
Antonio Romano, Mariana Di Fonso et al, Dept. Of Internal Medicine & Geriatrics, Allergy Unit, Rome, Italy.
Background: In some subjects, specific foods trigger anaphylaxis when exercise follows ingestion (specific food-dependent exercise-induced anaphylaxis, FDEIAn). Skin tests and RAST positivity to foods suggest an IgE-mediated pathogenic mechanism. Others suffer from anaphylaxis after all meals followed by exercise, regardless of the food eaten (non-specific FDEIAn). This study sought to identify the culprit foods with a diagnostic protocol.
Methods: They collected detailed histories and performed skin prick tests (SPT) with 26 commercial food allergens, prick plus prick tests (P+P) with 15 fresh foods (including 9 assessed with SPT), and RAST for 31 food allergens. Treadmill stress tests were administered after a meal without any positive food (food plus exercise challenge, FEC).
Results: Among the 54 patients, 6 could not recall any suspect food. The other 48 suspected a specific food in at least one episode. The most frequent were tomatoes, cereals and peanuts. 52 subjects were positive to at least 1 food (22 to more than 2), whereas 2 showed no positive results. All suspect foods were positive. SPT, P+P and RAST displayed different degrees of sensitivity. Each test disclosed some positives not discovered by others. 2 subjects reacted to FEC. Overall, 48 patients probably had specific FDEIAn.
Conclusions: In EIAn it is useful to test both in vivo and in vitro to an extensive panel of foods. Avoidance of foods associated with skin test and/or RAST positivity for at least 4 hours before exercise has prevented further episodes in all our patients with specific FDEIAn.
International Archives of Allergy and Immunology 125:3:2001, 264-272
A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants.
Scott H. Sicherer, MD, Terrence Furlong, MS, Anne Munoz-Furlong, BA et al, New York, NY.
Background: A voluntary registry of individuals with peanut and/or tree nut allergy was established in 1997 to learn more about these food allergies.
Objective: The purpose of this study was to elucidate a variety of features of peanut and tree nut allergy among the first 5149 registry participants.
Methods: The registry was established through use of a structured questionnaire distributed to all members of the Food Allergy and Anaphylaxis Network and to patients by allergists. Parental surrogates completed the forms for the children under the age of 18 years.
Results: Registrants were primarily children (89% of registrants were younger than 18 years of age; the median age was 5 years), reflecting the membership of the Network. Isolated peanut allergy was reported by 3482 registrants (68%), isolated tree nut allergy by 464 (9%), and allergy to both foods by 1203 (23%). Registrants were more likely to have been born in October, November, or December (odds ratio, 1.2, 95% CI, 1.18-1.23; P<. 0001). The median age of the reaction to peanuts was 14 months, and the median age of reaction to tree nuts was 36 months; these represented the first known exposure for 74% and 68% of registrants respectively. One half of the reactions involved more than 1 organ system, and more than 75% required treatment, frequently from medical personnel. Registrants with asthma were more likely than those without asthma to have severe reactions (33% vs. 21%; p < .0001). In comparison with initial reactions, subsequent reactions due to accidental ingestion were more severe, more common outside the home, and more likely to be treated with adrenaline.
Conclusion: Allergic reactions to peanut and tree nut are frequently severe, often occur on first known exposure, and can become more severe over time.
Reference: J Allergy Clin Immunol 2001; 108: 128-32
Early introduction of cereals into children's diets as a risk factor for grass pollen asthma.
A. Armentia, C. Banuelos, M. L. Arranz et al, Division of Clinical Immunology, Valladolid Univ., Spain.
Background: The prevalence of asthma has increased from 1950s to the 1990s. The relationship between diet and asthma is an area of controversy that has never been fully evaluated. Attempts at dietary prevention of asthma have produced conflicting results. We have recently identified allergens from cereals that show cross-reactivity with proteins in grass pollen. An early intake of cereals in the diet during early life might cause IgE sensitisation to cereals. It is not known wether such sensitisation predisposes to the development of allergy to pollen.
Methods: To test this hypothesis, a cross-sectional study and an observational case-control analysis of reviewed data were carried out on 16381 patients who had been admitted to their Allergy Unit between 1989 and 1999. All the patients underwent allergy tests to identify asthma risk factors. All information in their database was analysed using the SPSS computer system.
Results: There has been an increase of 7.8% in the incidences of allergic asthma and a 7.3% increase in asthma due to grass pollen in the last decade. Grass-pollen asthma was associated with sensitisation to cereals. The early introduction of cereals in the diet of children was found to be a risk factor for grass-pollen asthma (OR = 5.95; 95% CI 3.89-9.10)
Conclusions: These findings document the progression of allergic asthma during a decade in a large sample of people who were influenced by similar environmental conditions and studied with the same diagnostic methods. This study represents the largest database of patients in which a common food is shown to be a risk factor for asthma.
Reference: Clinical and Experimental Allergy, Vol. 31, and pp. 1250-1255
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