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previous  next Provided by/avec le support de :     S-221 87     Lund Sweden ARLS information : Myrna Mansson Get the paper version from your local Marketing representative. Find the address ont the net at http://www.astrazeneca.com/Marketing-worldwide AstraZeneca Respiratory Literature Service N°2   1999 (see other Expert comments on Asmanet) For many years, AstraZeneca Draco laboratories have brought to the asthmologist community an excellent "Respiratory Literature Service" (ARLS) with an alert to new references, selected summaries and comments by a group of experts. In 1997, AstraZeneca is extending this concrete service with Asmanet in order to take advantage of the Internet capabilities. The following comments have been edited ( HTML format) to smooth the reading with hypertext links to integrate the comment in the Asmanet server and the worldwide distributed library on asthma, such as : abstract of the commented paper, references as seen on Medline and others, author's e-mail ...   Title Authors Journal Reviewer 1 Effects of intranasal corticosteroids on adrenal, bone, and blood markers of systemic activity in allergic rhinitis Wilson AM et al J Allergy Clin Immunol 1998;102:598-604 Professor Estelle Simons 2 Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma Kon OM et al The Lancet 1998;352:1109-13 Professor Estelle Simons 3 Effect of nebulized ipratropium on the hospitalization rates of children with asthma Qureshi F et al New Engl J med 1998;339:1030-5 Professor Estelle Simons 4 Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: The rist results of ETAC ETAC Study Group Pediatr Allergy Immunol 1998;9:116-124 Professor Estelle Simons 5 Classification of asthma severity: should the international guidelines be changed? Sawyer et al Clin Exp Allergy 1998 Dec;28(12):1565-70 Ass. Professor Leif Rosenhall 6 Long-term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis Van Grunsven et al Thorax 1999 Jan;54(1):7-14 Ass. Professor Leif Rosenhall 7 The effects of regular inhaled formoterol, budesonide and placebo on mucosal inflammation and clinical indices in mild asthma. Wallin et al Am J Respir Crit Care Med 1999 Jan;159(1):79-86 Ass. Professor Leif Rosenhall 8 Do inhaled steroids cause osteoporosis? John H Toogood   Ass. Professor Leif Rosenhall 9 A comparison of two long-acting b -agonists, oral bambuterol and inhaled salmeterol in the treatment of moderate to severe asthmatic patients with nocutrnal symptoms Wallaert et al Respir Med 1999; 83:33 Professor Duncan Geddes 10 Sex differences in the use of asthma drugs: Cross sectional study M Sexton et al BMJ 1998;317:1434 Professor Duncan Geddes 11 Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthma Emerman et al Chest 1999; 115:92 Professor Duncan Geddes 12 Classification of asthma severity: Should the international guidelines be changed? Sawyer G et al Clinical and Experimental Allergy 28:1565, 1998 Professor Takateru Izumi 13 The effects of regular inhaled formeterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma Wallin A et al Am J Respir Crit Care med 158:79, 1998 Professor Takateru Izumi 14 Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma Jatakanon A et al Thors 54;108, 1999 Professor Takateru Izumi 15 Long term effects of inhaled corticosteroids in COPD: a meta analysis PM van Grunsven et coll. Thorax 1999; 54:7-14 Professor Philippe Godard 16 Dietary anti oxidants and magnesium in type 1 brittle asthma: a case control study JC Baker et coll Thorax 199; 54:115-118 Professor Philippe Godard AstraZeneca Draco laboratories is also supporting the European Federation of Asthma and Allergy Associations which can be seen at http://www.efanet.org/ Access for abstracts to Medline through Healthgate (http://www.healthgate.com/HealthGate/MEDLINE/search.shtml ) or through HealthWorld Medline Search (http://www.healthy.net/library/search/medline.htm ) or through http://www.ncbi.nlm.nih.gov/ ...

This study is welcome, as there are relatively few published studies of the effects of intranasal corticosteroids on adrenal, bone, and blood markers of systemic activity in allergic rhinitis, in comparison to numerous studies of the effects of inhaled corticosteroids on markers of systemic activity in asthma. Although intranasal corticosteroid doses are generally smaller than orally inhaled corticosteroid doses, nasal bioavailability may exceed lung bioavailability. Also, absorption from inflamed nasal mucosa may differ from absorption from normal nasal mucosa. While it is encouraging that the investigators studied patients with allergic rhinitis rather than healthy volunteers, a limitation of the study is that the severity of the allergic rhinitis was not assessed.

Neither budesonide 200 µg nor mometasone furoate 200 µg, nor triamcinolone acetonide 220 µg, all administered in aquaous formulation once daily, affected adrenal, bone, or blood markers after 5 days of treatment at steady-state. The outcomes assessed were 24 hour area under the curve plasma cortisol, 24-hour urinary cortisol/creatinine ratio, and plasma osterocalcin and blood eosinophil counts measured 24 hours after dosing.

Failure to find adrenal suppression, a sensitive and reproducible surrogate marker of the systemic bioactivity of corticosteroids, is somewhat reassuring. Ultimately, however, long-term studies of the safety of intranasal corticosteroids are needed in patients with allergic rhinitis. A recent example of this is the report of a significant suppression in linear growth of children receiving intranasal beclomethasone dipropionate for one year in a randomized, double-blind, placebo-controlled study¹.

Reference:

1. Rachelefsky GS, Chervinsky P, Meltzer EO, Morris RM, Seltzer JM, Skoner DP, et al. An evaluation of the effects of beclomethasone dipropionate aqueous nasal spray (Bancenase AQ) on long-term growth in children. J Allergy Clin Immunol 1998;101:S236.

Title (1): . Effects of intranasal corticosteroids on adrenal, bone, and blood markers of systemic activity in allergic rhinitis Wilson AM et al J Allergy Clin Immunol 1998;102:598-604 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Wilson AM; Sims EJ; McFarlane LC; Lipworth BJ
Address : Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Scotland.
Source : J Allergy Clin Immunol, 102(4 Pt 1):598-604 1998 Oct
Abstract
BACKGROUND: Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compared their systemic effects. OBJECTIVE: The purpose of this study was to compare the systemic bioactivity of aqueous formulations of intranasal budesonide, mometasone furoate (MF), and triamcinolone acetonide (TAA) in terms of adrenal, bone, and white blood cell markers. METHODS: Twenty patients with allergic rhinitis, mean age (SE) 35.7 (3.5) years were studied in a single-blind, randomized, 4-way crossover design, with treatments separated by 7-day washout periods, comparing placebo with budesonide 200 micro(g) once daily, MF 200 micro(g) once daily, and TAA 220 micro(g) once daily. After 5 days of treatment at steady-state, serial blood and urine samples were taken for 24 hours. Collective and fractionated measurements (daytime, overnight, and 8 AM) were done on plasma cortisol and urine cortisol/creatinine excretion. Plasma osteocalcin and blood eosinophil counts were measured at 8 AM. RESULTS: There was no significant difference between placebo and the active treatments with any of the markers of adrenal suppression. Mean values (SE) for 24-hour area under the curve plasma cortisol (nmol/L.hr) were placebo, 6312.9 (564.4); budesonide, 5908.8 (496.8); MF, 6374.1 (509.9); and TAA, 6239.2 (552.0). Twenty-four hour urinary cortisol/creatinine ratio (nanomoles per millimoles) showed placebo, 9.2 (0.5); budesonide, 8.5 (0.5); MF, 8.6 (0.4); and TAA, 8.6 (0.4). The diurnal circadian rhythm was unaffected, and there were only occasional patients with abnormally low cortisol values. There was also no suppression in terms of osteocalcin (placebo, 1.27 nmolL; budesonide, 1.22 nmol/L; MF, 1.33 nmol/L; and TAA, 1.24 nmol/L) and blood eosinophil count (placebo, 0.29 x 10(9)/L; budesonide, 0.27 x 10(9)/L; MF, 0.25 x 10(9)/L; and TAA, 0.24 x 10(9)/L). CONCLUSION: Neither budesonide, MF, nor TAA produced significant systemic suppression of adrenal, bone, or white blood cell markers at the doses studied....

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Effect-of-intranasal-corticosteroids-on-adrenal

In asthma, activated T lymphocytes play an important role in chronic allergic inflammation in the airways. CD4 T cells are an important source of eosinophil-regulating cytokines, their numbers are increased in bronchoalveolar lavage fluid, and bronchial biopsy samples from patients with asthma, the cells are activated in acute and severe asthma, and the number of cells correlates with eosinophil numbers and activation.

The investigators report modest efficacy of keliximab in middle-age, non-smokers with long-standing corticosteroid-dependent asthma. At baseline, despite ³ 1000 µg of inhaled corticosteroid daily, 5-30 mg prednisolone daily, and 4-19 puffs bronchodilator daily, these subjects had frequent symptoms and low FEV₁ . After a 2-hour intravenous infusion of keliximab, a chimeric human/macaque monoclonal antibody to CD4, they were observed for 24 hours in the hospital, then reassessed at 48 hours and at 7, 14 and 28 days. High-dose keliximab (3 mg/kg) improved symptoms (non-significant) and also improved morning and evening peak expiratory flows (p=0.005 and p=0.014, respectively) for 14 days after a single infusion. As expected, it also reduced the CD4 count in a dose-dependent manner, and did not affect CD8 counts. Interestingly, treatment with the antibody did not reduce blood eosinophil counts.

There were no serious adverse effects attributable to treatment. The authors excluded patients with a history of malignant disease, chronic hepatitis or HIV infection. In the discussion of their results, they caution that this immunosuppressant therapy would require a careful assessment of the benefit-no-risk ratio in each patient with asthma. It is of interest that patients with rheumatoid arthritis receiving monoclonal antibody treatment against CD4 in combination with other immunosuppressant therapy have not had any apparent significant increase in opportunistic infections or neoplasms¹.

At this time, specific targeting of CD4 lymphocytes by monoclonal antibodies should be considered to be experimental, but potentially useful, adjunctive treatment in the management of severe asthma.

Reference:

1. Moreland LW, Pratt PW, Bucy RP, Jackson BS, Feldman JW, Koopman WL. Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody: long-term follow-up of CD4 + T cell counts. Arthritis Rheum 1994;37:834-38

Title (2) : Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma Kon OM et al The Lancet 1998;352:1109-13 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Kon OM, Sihra BS, Compton CH, Leonard TB, Kay AB, Barnes NC
London Chest Hospital, UK.

BACKGROUND: There is substantial circumstantial evidence that CD4 lymphocytes have a role in the pathogenesis of chronic asthma. We investigated the efficacy and safety in severe corticosteroid-dependent asthma of a single intravenous infusion of keliximab (IDEC CE9.1), a chimeric monoclonal antibody to CD4. METHODS: 22 patients were recruited from two asthma clinics. In an ascending-dose design, the first eight patients were assigned 0.5 mg/kg keliximab (six) or placebo (two); the next seven were assigned 1.5 mg/kg (five) or placebo (two); and the last seven were assigned 3.0 mg/kg (five) or placebo (two). Masked data on safety for each dose group were assessed before progression to the next dose. Patients kept a daily symptom diary and measured morning and evening peak expiratory flow (PEF) at home. PEF and forced expiratory volume in 1 s (FEV1) were measured at follow-up clinic visits. FINDINGS: Patients given 0.5 mg/kg or 1.5 mg/kg keliximab and placebo recipients did not differ in change from baseline of PEF, FEV1, or symptom score. Those given 3.0 mg/kg keliximab differed significantly from placebo recipients in change in morning PEF (median area under curve [AUC] 445 vs -82.5, p=0.005) and evening PEF (median AUC 548 vs -85, p=0.014). Symptom score showed the same pattern (though differences did not achieve significance), but there was no difference in clinic FEV1. There were no serious adverse effects related to treatment. Two patients had mild exacerbations of eczema and one developed a transient maculopapular rash. All doses of keliximab were associated with a reduction from baseline in CD4 count. INTERPRETATION: Our findings raise the possibility that T-cell-directed treatment may be an alternative approach to the treatment of severe asthma.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...dose-ranging,-placebo-controlled+Kon

Many physicians prescribe nebulized ipratropium, in addition to nebulized albuterol, oxygen and oral corticosteroids, for children with acute asthma episodes. In previous smaller studies of ipratropium efficacy, no significant differences between treatment and control groups were found with regard to rates of hospitalization. In many of these studies, a relatively low dose of ipratropium bromide (250 µg) was administered, or a single dose was given, and the duration of observation was relatively brief. In two recent meta-analyses^1-2, investigators came to different conclusions with regard to the usefulness of ipratropium treatment in children with acute asthma.

This large, propspective, randomized, double-blind, placebo-controlled study in 434 "children" (age 2-18 years) is therefore of great interest. In this clinical trial, the addition of a nebulized solution of 500 µg (2.5 mL) of ipratropium to the second and third doses of albuterol, and prednisone, in the Emergency Department significantly reduced the overall rate of hospitalization and significantly reduced the need for hospitalization of children with severe asthma exacerbations, defined as peak expiratory flow <50 % predicted and an asthma score of 12-15 on a 15-point scale, The number of children with severe exacerbations who would need to be treated with ipratropium to prevent one hospitalization was 6.6 (95% confidence interval 3.7-29.4).

This study has important economic consequences for health care systems worldwide, as well as for children with asthma and their families.

References:

1. Osmond MH, Klassen TP, Efficacy of ipratropium bromide in acute childhoood asthma: a meta-analysis. Acad Emerg Med 1995;2:651-6
2. Plotnick LH, Ducharme FM. Should inhaled anticholinergics be added to b ₂-agonists for treating acute childhood and adolescent asthma? A systematic review. Br Med J 1998;327:971-7

Title (3): Effect of nebulized ipratropium on the hospitalization rates of children with asthma Qureshi F et al New Engl J med 1998;339:1030-5 (partial abstract from http://www.healthy.net/library/search/medline.htm )

N Engl J Med 1998 Oct 8;339(15):1030-5
Qureshi F, Pestian J, Davis P, Zaritsky A
Division of Pediatric Emergency Medicine, Children's Hospital of the King's Daughter, Eastern Virginia Medical School, Norfolk 23507, USA.

BACKGROUND: Anticholinergic medications such as ipratropium improve the pulmonary function of patients with acute exacerbations of asthma, but their effect on hospitalization rates is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled study of 434 children (2 to 18 years old) who had acute exacerbations of moderate or severe asthma treated in the emergency department. All the children received a nebulized solution of albuterol (2.5 or 5 mg per dose, depending on body weight) every 20 minutes for three doses and then as needed. A corticosteroid (2 mg of prednisone or prednisolone per kilogram of body weight) was given orally with the second dose of albuterol. Children in the treatment group received 500 microg (2.5 ml) of ipratropium bromide with the second and third doses of albuterol; children in the control group received 2.5 ml of normal saline at these times. RESULTS: Overall, the rate of hospitalization was lower in the ipratropium group (59 of 215 children [27.4 percent]) than in the control group (80 of 219 [36.5 percent], P=0.05). For patients with moderate asthma (indicated by a peak expiratory flow rate of 50 to 70 percent of the predicted value or an asthma score of 8 to 11 on a 15-point scale), hospitalization rates were similar in the two groups (ipratropium: 8 of 79 children [10.1 percent]; control: 9 of 84 [10.7 percent]). For patients with severe asthma (defined as a peak expiratory flow rate of <50 percent of the predicted value or an asthma score of 12 to 15), the addition of ipratropium significantly reduced the need for hospitalization (51 of 136 children [37.5 percent], as compared with 71 of 135 [52.6 percent] in the control group; P=0.02). CONCLUSIONS: Among children with a severe exacerbation of asthma, the addition of ipratropium bromide to albuterol and corticosteroid therapy significantly decreases the hospitalization rate.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Effect-of-nebulized-ipratropium+Qureshi

Approximately 40 % of infants with atopic dermatitis develop asthma by the age of 3-4 years. There is considerable interest in prevention of asthma in this high-risk population. In the 18-month ETAC Study, the relative risk for developing asthma in subjects allergic to grass pollen, house dust mite, or both allergens was significantly reduced by the H₁-receptor antagonist cetirizine, although in the intention-to-treat population, which included all infants with normal and elevated total or specific IgE, there was no significant risk reduction. This study extends the findings of two smaller studies published in the mid-1990s, in which intervention with the H₁-receptor antagonist ketotifen in infants with atropic dermatitis/family history of allergy and raised serum total IgE levels led to a significant decrease in the subsequent prevalence of asthma. ^1,2

The mechanisms underlying the asthma-preventing effects of H₁-antagonists are not entirely clear at this time. These effects are unlikely to be due to H₁-receptor blockade. Rather, they may be due to the anti-allergic and anti-inflammatory effects that can be documented after high-dose treatment with many H₁-antagonists. The subjects in the ETAC Study weighed 10-20 kg and received a total daily cetirizine dose of 5-10 mg, depending on weight - a high dose indeed. Despite this, the dropout rate was extremely low, and there were no significant neurologic, cardiac, or other adverse effects attributable to cetirizine.

The ETAC Study suggests that, in the twenty-first century, we may be able to use pharmacologic intervention to prevent the "allergic march" - development of one allergic disorder after another - in infants sensitized to common environmental allergens.

References:

1. Likura Y, Naspitz CK, Mikawa H, Talaricoficho S, Baba M, Sole D et al. Prevention of asthma by ketotifen in infants with atopic cermatitis. Ann Allergy 1992;68:233-6

Bustos GJ, Bustos D, Bustos GJ, Romero O. Prevention of asthma with ketotifen in Preasthmatic dhildren: a three-year floolw-up study. Clin Exp Allergy 1995;25:568-73

Title (4): Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: The rist results of ETAC ETAC Study Group, Pediatr Allergy Immunol 1998;9:116-124 (partial abstract from http://www.healthy.net/library/search/medline.htm )

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. METHODS: Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. RESULTS: In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7)...

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Allergic-factors-associated-with-the-development-of-asthma+ETAC

PEF may not reveal a chronic obstruction!

In this very important paper measurements of FEV₁ and PEF obtained from 1198 asthmatics were compared. The PEF values expressed as a percentage of predicted normal were generally considerably higher than the FEV₁ values.

The main goals for modern asthma treatment is to prevent severe exacerbations and chronic obstruction. A PEF value may seem normal while an obstruction can be detected by dynamic spirometry including FEV₁. The reason for this is obvious when you look at the flow volume curve.

The authors suggest that spirometry should be used instead of PEF when evaluating the effect of the treatment. Therefore, I recommend that PEF should be used by the Patients and Spirometry by the Supervisor (Specialists). The modern spirometer is cheap and easy to handle. It should be used by all doctors who are treating patients with chronic asthma, even GPs.

PEF may not reveal a chronic obstruction!

In this very important paper measurements of FEV₁ and PEF obtained from 1198 asthmatics were compared. The PEF values expressed as a percentage of predicted normal were generally considerably higher than the FEV₁ values.

The main goals for modern asthma treatment is to prevent severe exacerbations and chronic obstruction. A PEF value may seem normal while an obstruction can be detected by dynamic spirometry including FEV₁. The reason for this is obvious when you look at the flow volume curve.

The authors suggest that spirometry should be used instead of PEF when evaluating the effect of the treatment. Therefore, I recommend that PEF should be used by the Patients and Spirometry by the Supervisor (Specialists). The modern spirometer is cheap and easy to handle. It should be used by all doctors who are treating patients with chronic asthma, even GPs.

Title (5): Classification of asthma severity: should the international guidelines be changed? Sawyer et al (partial abstract from http://www.healthy.net/library/search/medline.htm )

Clin Exp Allergy 1998 Dec;28(12):1565-70
Sawyer G, Miles J, Lewis S, Fitzharris P, Pearce N, Beasley R
Department of Medicine, Wellington School of Medicine, New Zealand.
[Medline record in process]

BACKGROUND: International guidelines recommend that, in addition to symptoms and medication requirements, measurements of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) are necessary for the objective assessment of asthma severity. The guidelines suggest that parity exists between measurements of FEV1 and PEF when expressed as percentage of predicted normal values, and that asthma severity can be classified as mild, moderate or severe on the basis of FEV and PEF measurements of > 80%, 60-80% and < 60% of predicted values, respectively. OBJECTIVE: To determine the relationship between measurements of FEV1 and PEF when expressed as percentage predicted values. METHODS: A total of 1198 paired measurements of FEV1 and PEF were obtained from the medical records of a random sample of 25 adult asthmatic patients attending a hospital-based chest clinic. Measurements of lung function were expressed as a percentage of predicted normal values, using the European Respiratory Society prediction equations for PEF and FEV1. For the individual paired measurements, the mean differences between PEF and FEV percentage predicted were calculated. Measurements of lung function were used to determine asthma severity with <60%, 60-80%, and >80% predicted FEV1 and PEF values representing severe, moderate and mild asthma, respectively. The proportion of paired measurements in which differences in classification resulted from the use of FEV1 or PEF percentage predicted values was then calculated. RESULTS: In asthma of differing severity, there was considerable variability between measurements of FEV1 and PEF when expressed as percentage predicted values; calculation of the FEV1% predicted resulted in lower values than those of the PEF percentage predicted, with a mean difference of -17.2% (95% CI -16.3%, -18.1%). There was agreement in classification of asthma severity in only 49.9% (598/1198) of paired measurements. Different prediction equations, while variably altering the degree of misclassification, did not correct the basic differences in the assessment of asthma severity dependent on the use of FEV or PEF. CONCLUSION: FEV1 and PEF values, expressed as percentage predicted, are not equivalent. Pending further evaluation, the authors suggest that published asthma guidelines should avoid the assumption of parity between these two measurements.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Classification-of-asthma-severity

When a significant effect is not clinically relevant

The group of smokers who are sensitive for the "amphysematos" effects of tobacco smoke have a very slow continuos deterioration of the lung function. The main goal for treatment of these patients is to stop smoking before the lung function is too much deteriorated. If they stop before the FEV₁ decreases below 50 % of predicted, the effect of the smoking and the lung damage is rather neglectable.

As smoking cessation is sometimes difficult and time consuming there are several attempts from the industry to introduce a pharmaceutical treatment instead. Inhaled steroids may slow down the progress of the diminishing lung function. This has been shown in two huge studies financed by pharmaceutical companies, the EUROSCOP and ISOLDE study. Grunsven et al. found the same result in a meta-analysis of three earlier smaller studies.

Obviously inhaled steroids have a significant effect, particularly during the first year in slowing down the decline of the FEV₁. However, even if this effect is significant, the effect is small from a clinical point of view. The progression of lung damage is not stopped and respiratory insufficiency, is not prevented - only postponed. We should hesitate to recommend the general use of inhaled steroids, which are excellent drugs in asthma, for the treatment of patients with chronic bronchitis who continue smoking. Instead, we should try harder to support the patient in smoking cessation before the final catastrophe is there.

Title (6): Long-term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis Van Grunsven et al (partial abstract from http://www.healthy.net/library/search/medline.htm )

Thorax 1999 Jan;54(1):7-14
van Grunsven PM, van Schayck CP, Derenne JP, Kerstjens HA, Renkema TE, Postma DS, Similowski T, Akkermans RP, Pasker-de Jong PC, Dekhuijzen PN, van Herwaarden CL, van Weel C
Department of General Practice and Social Medicine, University of Nijmegen, The Netherlands.

BACKGROUND: The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?" METHODS: A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated. RESULTS: No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group. CONCLUSIONS: This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Long-term-effects-of-inhaled-corticosteroids

Are long acting b ₂ agonists also antiinflammatory?

It is much more glamorous for an asthma drug to be "anti-inflammatory" than only bronchodilating. After many decades of clinical experience, theophylline is now proudly positioned as "anti-inflammatory". For us old enough to remember the times that we did not have inhaled steroids and all asthmatics were on theophylline, we find it hard to believe that its anti-inflammatory effect is of high clinically relevance. Generally, bronchodilator drugs should not be considered "anti-inflammatory".

However, in this very thorough and scientific study it is shown that treatment with formoterol has a significant effect on some of the asthma inflammatory cells in the bronchial mucosa. Formoterol is a rather new and very interesting drug with a quick onset and a long duration. The described anti-inflammatory effects might be due to a property of the drug itself. Alternatively, they might be a consequence of the reduced asthma symptoms resulting from the preventive effect of formoterol. Which of these explanations is true is not easy to judge.

Moreover, it should be remarked that the eventual anti-inflammatory activity of the b ₂-agonist formoterol is much lower compared to that of the inhaled steroids. The study is very interesting and should be used in discussions about the anti-inflammatory effects of theophylline and bronchodilators in general..

Title (7): The effects of regular inhaled formoterol, budesonide and placebo on mucosal inflammation and clinical indices in mild asthma. (partial abstract below from http://www.healthy.net/library/search/medline.htm )

Am J Respir Crit Care Med 1999 Jan;159(1):79-86
Wallin A, Sandstrom T, Soderberg M, Howarth P, Lundback B, Della-Cioppa G, Wilson S, Judd M, Djukanovic R, Holgate S, Lindberg A, Larssen L, Melander B
Department of Respiratory Medicine and Allergy, University Hospital, and National Institute of Occupational Health, Medical Division, Umea, Sweden.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...effects-of-regular-inhaled-formoterol

John Toogood has written very important papers about inhaled steroids. He was one of the first to see the potentialities of these drugs and to assess their pro and cons.

In this very thorough paper he discusses the risk for developing osteoporosis, particularly the risk for females who use inhaled corticosteroids long-term. He stresses that a reduction in bone mineral density occurs particularly during the first 6-12 months of regular corticosteroid use. He discusses the different steroids and he states that a dose not higher than 1000 µg of any of the inhaled steroids is quite safe. Nevertheless, the steroid dose should be kept as low as possible. This can be achieved with help of steroid sparing drugs such as the long-acting b ₂-agonists but also the new antileukotrienes.

There are a lot of important observations in the paper. For me it was, for example, very interesting to read that the use of a spacer increases the risk for systemic effects. The reason for this is the higher uptake in the systemic circulation via the lung because the lung deposition of a drug is higher when a spacer is used. Of course high lung deposition is good for the patient if the dose given can be reduced.

Moreover, the paper shows that if the currently avaible inhaled corticosteroids are used in a correct way, i.e., according to the guidelines, the risk for severe side-effects is very low. Nevertheless, it is important to keep always in mind that there is a potential risk when high doses have to be given. This risk should never be neglected. When introducing new inhaled steroids the potential risk for long-term side-effects must always be kept in mind even if short-term studies did not reveal any side-effects.

Title (8): Do inhaled steroids cause osteoporosis? John H Toogood (partial abstract from http://www.healthy.net/library/search/medline.htm )

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...do-inhaled-steroids-cause-osteoporosis

This double-bind study compared six weeks of once daily oral bambuterol with twice daily inhaled salmeterol in 117 patients. All had moderate to severe asthma treated with 800 to 2000 µgs of inhaled steroid and/or up to 20 mgs of oral steroids daily. There was a significant improvement in peak flow, day time symptoms and nocturnal wakenings and reduction in rescure bronchodilator with both treatments and there was no difference between the two treatments.

Although the study did not report any significant differences in adverse effects overall the analysis was somewhat unclear. The most frequent events involved the respiratory system (21 bambuterol, 11 salmeterol), headache occurred in 6 people taking bambuterol and 2 taking salmeterol. Tremor scores were low both before and after treatment and were not different between the two groups.

With the increasing recognition that long acting b -agonists are more effective in uncontrolled asthma than an increase in inhaled steroids, prescribing of long acting b -agonists is likely to increase and bambuterol will be preferred by many because of the simple once daily oral administration and relatively low cost.

Title (9): A comparison of two long-acting b -agonists, oral bambuterol and inhaled salmeterol in the treatment of moderate to severe asthmatic patients with nocutrnal symptoms Wallaert et al Respir Med 1999; 83:33. (partial abstract from http://www.healthy.net/library/search/medline.htm )

...

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...comparison-of-two-long-acting

.This cross sectional study assessed the use of asthma drugs according to gender in a primary care setting. People aged between 20 and 54 who had received an asthma drug during the year before the study were sent a qustionnaire and 70 % responded. The resulting 237 subjects with confirmed asthma had similar levels of asthma severity and frequency of current smoking. b -agonist and inhaled steroid use was similar for both genders. The striking finding was that women consulted their doctor more often and were five times more likely to receive oral steroids than men. This finding was independent of age, current smoking, or asthma symptoms while the use of oral steroids was closely related to the frequency of visits to the doctor. While this surprising finding may be due to differences in behaviour of either women or their doctors, the possibility that the women’s asthma was worse (although equally well controlled) cannot be excluded. Which ever explanation is true this finding clearly needs to be confirmed and explained.

Title (10): Sex differences in the use of asthma drugs: Cross sectional study M Sexton et al BMJ 1998;317:1434 (partial abstract from http://www.healthy.net/library/search/medline.htm )

BMJ 1998 Nov 21;317(7170):1434-7
Sexton M, Althuis MD, Santanello N, Hyndman S, Williams R, Schmeidler D
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
mailto:msexon (at) epl.umaryland.edu

OBJECTIVES: To assess the use of asthma drugs by men and women with asthma and to identify sex specific predictors for the use of oral steroids. DESIGN: Cross sectional study. SETTING: Six general practices in East Anglia. SUBJECTS: 103 men and 134 women aged 20-54 with asthma. MAIN OUTCOME MEASURES: Self reported use of agonists, inhaled steroids, and oral steroids. RESULTS: No sex difference was found in use of agonists or inhaled steroids. However a strong association existed between sex and oral steroid use. 40 (30%) women reported using oral steroids compared with nine (9%) men. Women were more than five times (odds ratio=5.5, 95% confidence interval 2.2 to 13.7) more likely to report use of oral steroids than men after asthma symptoms, age, visits to the general practitioner in previous six months, and time since diagnosis of asthma were controlled for. Women who had visited the general practitioner for asthma one or more times in the previous six months were four times (3.9, 1.6 to 9.5) as likely to report use of oral steroids. In addition, more frequent visits to the general practitioner for asthma were related in a dose-response manner to a greater likelihood of using oral steroids among women after asthma symptoms, age, and time since diagnosis were controlled for. This relation was not observed among men. CONCLUSION: Women used oral steroids more than men. The more frequent consultations with a doctor by women may result in more requests for oral steroids or doctors may preferentially prescribe oral steroids to women.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/...Sex-differences+asthma+Sexton

160 patients presenting to an Emergency Department with acute asthma were randomised to receive nebulised Albuterol either 2.5 or 7.5 mgs every twenty minutes for a total of three doses. All patients received oral Prednisolone. There were no significant differences in any of the measured variables and the authors concluded that there was no advantage in delivering the higher dose.

This study is yet another important contribution to information on appropriate dosing in the treatment of asthma. For both b -agonists and inhaled steroids there has been a tendency to believe that more is better in spite of the fact that the plateau on the dose response curves for both agents is reached at relatively low doses. While it is possible that some individual patients with very severe asthma may need high doses there is no evidence justifying routine prescription of the higher doses. Lower doses are cheaper and safer.

Title (11): Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthma Emerman et al Chest 1999; 115:92 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Chest 1999 Jan;115(1):92-6
Emerman CL, Cydulka RK, McFadden ER
Department of Surgery, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109-1998, USA. cemerman (at) metrohealth.org

PURPOSE: The optimal dose of albuterol to use in the treatment of acute asthma has yet to be established. The National Asthma Education and Prevention Program (NAEPP) recommends a starting dose of 2.5 to 5 mg of aerosolized albuterol every 20 min, although European authorities recommend higher doses. The purpose of this study was to compare 2.5 vs 7.5 mg of nebulized albuterol for the treatment of acute asthma. SUBJECTS: We studied 160 patients presenting to the emergency department with acute asthma. METHODS: On enrollment, patients underwent baseline testing, including initial spirometry. All patients received prednisone, 60 mg, orally. Patients then received in a randomized, double-blinded fashion, nebulized albuterol either 2.5 or 7.5 mg every 20 min for a total of three doses. Spirometry was repeated after each of the first two treatments and again 40 min after completion of the three treatments. RESULTS: The pretreatment FEV1 was 36.9+/-16.6% of predicted normal in the low-dose group vs 41.5+/-15.4% of predicted normal in the high-dose group (not significant [NS]). The patients in the low-dose group had a 50.3+/-62.6% improvement in FEV1 pretreatment to post-treatment, whereas those in the high-dose group had a 44.6+/-48.2% improvement in FEV1 (NS). There was no difference in the admission rate in the low-dose group (43%) as compared with that of the high-dose group (39%; NS). CONCLUSION: We conclude that there is no advantage to the routine administration of doses of albuterol higher than 2.5 mg every 20 min. It is possible that there may be an advantage in the most severely obstructed patients, although this study did not enroll enough patients with very severe asthma to evaluate this. As has been previously demonstrated, patients who subsequently require admission have a diminished response to albuterol. This decreased responsiveness is seen with the first aerosol administration and is unaffected by increasing the dose.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...Comparison+albuterol+acute-asthma+Emerman

FEV₁ and PEF have been recommended as indices of asthma severity in international guidelines. Clinically, these two indicators have been assumed to yield equivalent values when expressed as percentage predicted and have been used interchangeable.

Based on an analysis of 1.198 measurements performed on 26 asthma patients, it was found that FEV₁ and PEF expressed as percentages predicted do not show parity. This is a very important clinical finding, worth special attention.

Further studies are required to determine the relative accuracies of FEV₁ and PEF as indicators of asthma severity.

Title (12): Classification of asthma severity: Should the international guidelines be changed? Sawyer G et al Clinical and Experimental Allergy 28:1565, 1998 (partial abstract from http://www.healthy.net/library/search/medline.htm )

see Title 5

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...asthma-severity+Sawyer

In the management of chronic asthma, regular inhaled corticosteroids have been recommended for the control of airway inflammation and short-acting b ₂ -adrenoreceptor agonists for quick-relief of acute bronchoconstriction.

This central dogma should be changed with the progress of clinical research. The authors’ examination of biopsy specimens revealed that regular inhalation of the long-acting b ₂ -adrenoreceptor agonist formoterol decreased inflammatory cells such as mast cells and eosinophils in the mucosa. These findings indicate the effectiveness of regular use of long-acting b ₂ -adrenoreceptor agonists. Hopefully this will lead to a wider choice of drugs for the management of asthma.

Title (13): The effects of regular inhaled formeterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma Wallin A et al Am J Respir Crit Care med 158:79, 1998 (partial abstract from http://www.healthy.net/library/search/medline.htm )

see Title 7

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...formeterol+budesonide+placebo+Wallin

It is of the utmost clinical importance to prescribe the minimal effective dose of inhaled steroids to suppress airway inflammation.

In this study the authors examined the usefulness of exhaled nitric oxide, methacholine airway responsiveness and sputum eosinophils as indicators of airway inflammation during treatment with different doses of inhaled budesonide.

The results show that especially the number of eosinophils in induced sputum is a useful indicator. Further studies are awanted to establish whether sputum eosinophilia is a simple and useful indicator for the determination of a patients’ minimal effective dose of inhaled steroid.

Title (14): Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma Jatakanon A et al Thors 54;108, 1999 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Thorax 1999 Feb;54(2):108-14
Jatakanon A, Kharitonov S, Lim S, Barnes PJ
Department of Thoracic Medicine, Imperial College School of Medicine at National Heart and Lung Institute, London, UK.

BACKGROUND: It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed. METHODS: The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC20) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 micrograms/day budesonide (n = 8), 400 micrograms/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 micrograms budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia. RESULTS: There were significant improvements in FEV1 following 400 micrograms and 1600 micrograms budesonide (11.3% and 6.5%, respectively, p < 0.05). This was accompanied by significant reductions in eosinophil numbers in induced sputum (0.7 and 0.9 fold, p < 0.05). However, levels of exhaled NO were reduced following each budesonide dose while PC20 was improved only with 1600 micrograms budesonide. These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 micrograms daily. CONCLUSION: Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...budesonide+markers+atirway+asthma+Jatakanon

In our daily practice, most COPD patients are regularly treated with inhaled corticosteroids. However, the clinical results are not as encouraging as in asthmatics. National and international recommendations are not clear and state that evidence of beneficial effects has not yet been established. Therefore, good clinical studies are needed. The current treatments in COPD range from smoking cessation for all including the mildest patients to long term treatment with oxygen at home for the severe patients.

This paper is interesting because it concentrates only on COPD and inhaled steroids. Moreover it has been well conducted. Especially the patient selection was good because only studies with patients having strictly defined moderate to severe COPD were included in the meta-analysis. In many studies phenotypes of patients are not well established. However, it is absolutely necessary to include additional parameters in the description of the patients COPD, namely - at least - assessment of eosinophils in bronchial secretion (either induced sputum or bronchial endoscopy) and TLCO (transfer factor for carbon monoxide).

In most studies, the severity of the COPD is solely described by FEV₁ and the only parameter to be analysed is FEV₁. However, van Grunsven et al. also evaluated exacerbations although they underline that the definition of exacerbations differs from one study to the other.

The authors found three full length papers and two abstracts of studies with a duration of at least 24 months. From these 5 studies, two studies were not suitable for meta-analysis because they were not randsomised, placebo controlled trials. What does it mean that only five studies about COPD and corticosteroids could be found? Was the quality of studies published as an abstract too low so they were rejected as full length paper? Are there studies available which were never submitted for publication because the results were negative?

There is great interest in clinical research of COPD. Many clinicians look forward to the publication of all the EUROSCOP study (EUropean Respiratory Society study on Chronic Obstructive Pulmonary disease).

Note from Astra: The EUROSCOP study has been accepted for publication by the New England Journal of Medicine.

Title (15): Long term effects of inhaled corticosteroids in COPD: a meta analysis PM van Grunsven et coll. Thorax 1999; 54:7-14 (partial abstract from http://www.healthy.net/library/search/medline.htm )

see Title 6

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...corticosteroids-in-COPD+van-Grunsven

The diet hypothesis of asthma is a long story. Since 1991, a potential role of diet in respiratory disease has been recognized. An association may exist between the deficient intake of certain nutrients and lung disease. However, the up to date results are confusing. Also this paper does not provide clear evidence to support the diet hypothesis.

Several components of the diet have been suggested to play a role in asthma. Burney et al., for example, suggested that a low salt intake was a risk factor to develop (?) asthma. Von Mutius et al. suggested a role for margarine. Moreover, some epidemiological data favour of a protective role of fish consumption. However, today there is no clear scientific support for these hypotheses.

Baker et al. conducted a dietary survey in which they analysed five day weighed records. These surveys are difficult to conduct from a methodological point of view. In the discussion section Baker et al. address several issues such as powering of the study, adjusting for smoking habits, under-reporting of food intake and the use of serum levels as an indication of dietary intake. Altogether, there are too many of such issues to allow a clear interpretation of the results.

The authors conclude that the study supports the hypothesis that intake of vitamin A and E are deficient in patients with brittle asthma. They recommend to perform a prospective clinical trial. However, the results are not clear enough to allow such a recommendation.

The study by Baker et al. reminded me of a study which I conducted a long time ago. The aim was to test the hypothesis that supplementation with a mixture of selenium, vitamin A, C, and E improved asthma (brittle asthmatics were not included). The results have never been published because they were negative and therefore the sponsor did not agree upon publication.

The authors write: "Nutrient deficiency and the resultant reduced antioxidant activity may enhance asthmatic inflammation, consequently contributing to bronchial hyperreactivity in this groups of patients" (i.e., in brittle asthma). However, reduced antioxidant activity can not only be overcome by vitamins but also by other compounds such as flavonoids in red wine. Beneficial effects of antioxidants in wine have been suggested by cardiologists. They observed that the French had a lower risk for cardiovascular diseases than other peoples (the French paradox). It would be interesting to perform a survey of wine consumption in asthmatics………

References:

1. Am J Respir Crit Care Med 1994 June; 149(6):1426-33
   Dietary sodium intake, airway responsiveness and cellular sodium transport.
   Tribe RM, Barton JR, Poston L, Burney PG
2. E von Mutius
   Lancet 1998 Mar 21;351(9106):862-6
   Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany.
   Von Mutius E, Weiland SK, Fritzsch C, Duhme H, Keil U
3. Atherosclerosis 1997 Nov;135(1):93-102
   Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro
   Kerry NL, Abbey M

Title (16): Dietary anti oxidants and magnesium in type 1 brittle asthma: a case control study JC Baker et coll Thorax 199; 54:115-118 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Thorax 1999 Feb;54(2):115-8
Baker JC, Tunnicliffe WS, Duncanson RC, Ayres JG
Brittle Asthma Unit, Birmingham Heartlands Hospital, UK.

BACKGROUND: Type 1 brittle asthma is a rare form of asthma. Atopy, psychosocial factors and diet may contribute to this condition. As increased dietary magnesium has a beneficial effect on lung function and selenium, vitamins A, C and E have antioxidant properties, a study was undertaken to test the hypothesis that patients with brittle asthma have diets deficient in these nutrients compared with subjects with non-brittle asthma and healthy adults. METHODS: A case control study of the dietary intakes of 20 subjects with brittle asthma, 20 with non-brittle asthma, and 20 healthy adults was performed using five day weighed dietary records. Intake of magnesium was the primary outcome measure with selenium and vitamins A, C and E as secondary outcomes. Serum levels were measured at the same time as the dietary assessment. RESULTS: Sixty subjects (27 men) of mean age 49.5 years were recruited and completed the study. Subjects with brittle asthma had statistically lower median dietary intakes of vitamins A and E than the other groups (vitamin A: brittle asthma 522.5 micrograms/day, non-brittle asthma 869.5 micrograms/day, healthy adults 806.5 micrograms/day; vitamin E: brittle asthma 4.3 mg/day, non-brittle asthma 4.6 mg/day, healthy adults 4.5 mg/day). Median dietary intakes for the other nutrients were not significantly different between groups. Serum levels were within normal ranges for each nutrient in all subjects. Intakes less than the reference nutrient intake (RNI) for magnesium and vitamins A and C, and less than the safe intake (SI) for vitamin E were more likely in patients with brittle asthma than in those with non-brittle asthma. CONCLUSION: Nutrient deficiency and reduced antioxidant activity may contribute to disease activity in type 1 brittle asthma, although a prospective study of replacement therapy will be needed to confirm this hypothesis.

... for the complete abstract, please enquire http://www.ncbi.nlm.nih.gov/htbin-post/...dietary-anti-oxidants+asthma+Baker

. ARLS   Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 1er Mars 1996 -Dernière mise à jour: 16/05/00
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