March 2009
Claude MOLINA and Franz MARRACHE
- Broccoli for the treatment of respiratory allergy
- Physical Exercise and Asthma Exacerbations in Older Women
- Drugs as risk factors of severity for Food Anaphylaxis in adults
- Antibiotics in Asthma and Atopic Dermatitis
- Urinary Biomarkers detected by NMR in an experimental model of Asthma
Broccoli for the treatment of respiratory allergy
Oxidative stress is an asthma trigger and constitutes one of the principle mechanisms of the pro-inflammatory effect of atmospheric pollutants such ozone and particles. Phase 2 detoxification enzymes abrogate this effect by eliminating oxygen reactive metabolites. Sulfopharane, an isothiocyanate present in broccoli sprouts and essentially identified as an anti-cancer agent, is a natural inducer of these enzymes. So this randomised, placebo-controlled study, carried out by Marc A. Riedla et al on the antioxidant effects of broccoli (Oral sulforaphane increases Phase II antioxidant enzymes in human upper airway. Clin. Immunol. 2009; 130 : 244-251) deserve a special mention.
From a standardised broccoli sprout homogenate (BSH), increasing doses of oral Sulfopharane were given to 60 individuals. Then were analysed the effects of Sulfopharane on expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxydoreductase (NQO1) and hemo-oxygenase-1 (HO1) enzymes in upper airways.
RNA expression for these Phase II enzymes was measured in nasal lavage fluid cells by Real-Time Polymerase-Chain-Reaction (PCR), before and after administration of Sulfopharane.
Administration of increasing doses of Sulfopharane was well tolerated and showed a dose-dependent relationship with the expression of detoxification enzymes, the strongest induction having been obtained with a preparation corresponding to 200g of broccoli.
By contrast, no induction was observed after the ingestion of a lucerne homogenate, which lacks Sulfopharane. By the light of these results, the authors concluded that Sulfopharane, present in broccoli sprouts, was a useful therapeutic agent for allergic manifestations in upper airways, due to its antioxidant effects. We may then advise our European asthmatic patients to eat a lot of cabbage, even Brussels sprouts, since our American colleagues from Los Angeles advise it!
Physical Exercise and Asthma Exacerbations in Older Women
A prospective study carried out in Barcelona, Paris (Villejuif) and Boston (USA), including a group of patients from an American cohort of nurses, has attempted to ascertain whether physical activity could prevent Asthma exacerbations (J. Garcia-Aymerich et al. Prospective study of physical activity and risk of asthma exacerbations in older women. AJRCCM 2009; ahead of print; February 26).
This group of 2818 women, whose mean age was 63 years, was monitored for 2 years, between 1998 and 2000, 71% of the cases being mild or moderate persistent asthma. Physical activity was estimated by a validated individual questionnaire and categorised in quintiles. Median physical activity corresponded to a brisk 20 minute-long walk 3 times weekly.
Asthma exacerbations were recorded from hospitalisations, emergency department or office visits. Asthma severity, treatments regularly used, previous exacerbations, socio-demographic factors, smoking habits and all other potential confounding factors were taken into account in the statistical analysis. It was apparent that higher was physical activity, lower was risk of asthma exacerbations. Likewise multivariate logistic regression model significantly showed that higher was physical activity, lower was risk of hospitalisation.
These results were not different upon stratification in terms of age, body mass index, inhaled corticosteroid therapy, previous hospitalisations or smoking habits (1 woman out of 2 had former smoking habits, and 6% were current smokers).
Once again this article highlights the favourable effects of physical exercise upon evolution of asthma, and should be pointed out in parallel with the recent publication by L. Byberg (Total mortality after changes in leisure time physical activity in 50 year old men : 35 year follow-up of population based cohort. Br. Med. J. 2009 ; 338 : b688) which showed that in a sample of 2205 older men, aged 50, physical activity prolonged life by 1.1 to 2.3 years (depending on its more or less intensity), which is similar to the effect of smoking cessation.
Drugs as risk factors of severity for Food Anaphylaxis in adults
In a case-control epidemiological study carried out between 1995 and 2008, Denise Moneret-Vautrin, from Nancy University, France, who is a name in the field of Food Allergy collected 76 cases of Food-induced Anaphylaxis (FIA) compared by multivariate analysis with 237 cases of moderately severe Food Allergy (MSFA). (D.Moneret-Vautrin and C. Latache in Bulletin de l¡¯Acad. Natl Med 2009; in print)
The frequency of FIA was 17% in the young, most frequently atopic adult, and 54.6% in people over 45 years of age in whom endogenous and exogenous factors favour Anaphylaxis. Among the latter, the intake of drugs associated with food allergens was systematically analysed. It became apparent that such intake does not vary with age, but it characterises 40.8% of cases of FIA and only 14.9% of cases of MSFA.
Four types of drugs were incriminated in this association with FIA: Aspirin, in 15.6% of cases; Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), in 6.6%; ¦Â-blockers, in 10.5%, and Angiotensin Converting Enzyme Inhibitors (ACEI), in 5.3%. All of these percentages were statistically significant, in comparison with those of MSFA, in which drugs were only associated in 1.7%, 0.9%, 1.7% and 0.4% of the cases, respectively (p¡Ü 0.003).
No other drug was associated with 311 remaining cases of FIA or MSFA.
By contrast, an association with the allergen, alcohol and above all, physical exercise, was observed in, respectively, 10.5% and 27.6 % of FIA cases and only in 0.4 and 8.1% of MSFA cases, (p¡Ü 0.0005).
Pathogenic mechanisms of FIA are then discussed for each of the 4 types of drugs.
Prevention involves, in the young adult, measures excluding intake of aspirin or NSAIDs before meals, when a food allergy is suspected. In older patients with high blood pressure or cardiac disease, eviction or utilisation of ¦Â-blockers and ACEI requires a discussion of the benefit / risk ratio between Allergists and Cardiologists, since there is an ample choice of useful pharmacological classes of drugs .
This important publication, which includes more than 300 cases of food allergy collected over a course of 13 years and is based upon an indisputable statistical analysis, reflects the vast experience of the authors and draws attention against the risks of excessive drug intake, which is frequent in the elderly and which may be responsible for severe episodes in allergic patient.
Antibiotics in Asthma and Atopic Dermatitis (A.D.)
Following their bibliographic research on behaviour of Allergists towards antibiotics for Asthma or A.D., the authors (M.S. La Shell and S. Tankersley. Antibiotics for the allergist. Part 2. Ann. Allergy Asthma Immunol. 2009 ; 102: 1-8) stated 3 principles reflecting a consensus on this issue:
1) Antibiotics are not indicated for the current treatment of Asthma
2) In atopic dermatitis, although bacterial colonisation with Staphylococcus aureus is frequent (90% of cases) and is a severity factor of the disease, antibiotics are rarely necessary, since the usual treatment of A.D. is usually sufficient.
3) If antibiotics are required in some cases, the choice must be made amongst the different pharmacological classes. Macrolides, which have immuno-modulatory and corticosteroid-sparing effects, may have a important role. The main structure of these antibiotics is a lactone ring of 14 to 16 atoms: 14 for erythromycin or clarythromycin, 15 for azithromycin. Only the 14 and 15 atom-containing compounds are active against Haemophilus influenzae or Mycoplasma pneumoniae or Chlamydia pneumoniae, and have immuno-modulatory and anti-inflammatory properties;
Josamycin or spiramyin, which contain 16 atoms, do not seem to have these effects. Let us remember that macrolides are not effective against Pneumococci.
In terms of Asthma, macrolides such as clarythromycin, might be useful for certain sub-populations of poorly-controlled asthmatic patients in whom there is a predominant neutrophilic inflammation and increased IL-8 production, as detected in the sputum. However, one must acknowledge that the set of trials with antibiotics is not convincing, even when the detection of infection is carried out by using PCR, which is more sensitive than simple serology.
In terms of A.D., frequent bacterial colonisation might justify usefulness of 1st or 2nd generation cephalosporins, but the discrimination between colonisation and superinfection is difficult to assess.
Overall, clinical trials using systemic or topical antibiotics did not demonstrate better efficacy than usual skin care and local intermittent treatments with corticosteroids or tacrolimus in the severe forms (Let us recall that tacrolimus has a structure which issimilar to that of macrolides, but with 23 atoms).
A table summarising the antibiotic pharmacological classes completes this set of interesting meta-analyses.
Urinary Biomarkers detected by NMR in an experimental model of Asthma
In search for non-invasive markers of asthma exacerbations and aware of uncertainty of sputum and exhaled NO analyses in humans, a group of Canadian scientists decided to study inflammation and bronchial hyperreactivity by urinary metabolites using spectroscopic analysis by Nuclear Magnetic Resonance imaging (NMR) in experimental animal models of ovalbumin-induced asthma (E.J. Saude et al. Metabolomic biomarkers in a model of asthma exacerbations. AJRCCM 2009; 179 : 25-34).
Five groups of guinea pigs were used: Controls, Controls treated with dexamethasone, Ovalbumin Sensitized (S), Hyperreactive (HR)/sensitized and challenged and HR treated with dexamethasone. Bronchial reactivity was measured using histamine challenge and inflammation was analysed by quantification of bronchial eosinophils. Simultaneously, about 50 urinary metabolites were measured using 3 or 4 regions of the spectrum obtained by NMR. The authors hypothesised that upper airway inflammatory cells would induce unique urinary changes in metabolic spectra, thereby allowing the discrimination between the different categories of animals. This hypothesis was confirmed since urinary metabolites significantly correlated with functional and bronchial cellular changes,
Several metabolic pathways were involved. Thus, HR guinea pigs had lower levels of glucose than S ones, probably due to glycolysis of fatty acids. Creatine levels were lower than normal in HR but not in S or controls, likely due to smooth muscle bronchial constriction. Tyrosine levels were decreased in HR, in relation with the metabolic activity of eosinophils. By contrast, the levels of sarcosin, an intermediate metabolite between choline and glycine, found in muscles and which has a role in neurotransmission, were elevated in HR and decreased in the corticosteroid group.
Dexamethasone induced a rapid decrease in bronchial hyperreactivity, but without reduction of eosinophil number in broncho-alveolar lavage fluid.
Overall, this panel of biomarkers allowed discrimination between inflammation and bronchial reactivity. Thus, this technique is a promising one and might be useful in a human clinical context, particularly in children, given its non-invasive nature.
Source: CEFCAP
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