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Claude MOLINA & Jacques GAYRAUD

1. Bitter taste and bronchospasm
2. Occupational asthma : the best and safest diagnosis criteria
3. Asthma to Alternaria
4. Attendance of day care centres and prevalence of childhood eczema
5. Indoor Air Quality (IAQ) and childhood asthma : variations between urban and rural areas


1.    Bitter taste and bronchospasm

Theme : Asthma
Key words : Bitter taste, taste enhancer, bronchodilation

The bitter taste receptors located on the tongue are meant, from a practical point of view, to avoid ingesting toxic substances. The original discovery, by a Baltimore University (USA) team of scientists, of the same receptors on the airway smooth muscle (ASM) (Deepak.A.Deshpande et al. Nature Medicine 2011/16/11  November 1299-1304) suggests that their purpose is to avoid inhaling irritating products (such as air pollutants), leading when provoked to ASM contraction and bronchospasm. In other words and to put it more simply, bitter taste and bronchospasm : two sides of a coin.

The other paradoxical and unexpected discovery of this study is that taste enhancers, such as artificial sweeteners (saccharine) or bitter sapid compounds like denatonium and chloroquine which act through a complex molecular mechanism associated to the opening up of calcium channels, lead when activated to a bronchodilation threefold greater than that provoked by β2-agonists (albuterol).

Besides, in confirmation of that notion is the authors’ observation that inhaling those bitter taste enhancers (chloroquine as well as denatonium) decreased airway obstruction in a mouse model of ovalbumine-triggered asthma.

Given the existence of a thousand-odd natural or synthetic bitter tastants, we realize that their bronchodilating activity, stronger than β2-agonists, constitutes a particularly promising and original research path.


2.    Occupational asthma : the best and safest diagnosis criteria

Theme : Asthma, occupational allergies
Key words : Occupational asthma, bronchial hyperresponsiveness, sputum eosinophils, sputum neutrophils, skin prick tests, specific IgEs

Montreal’s Hopital du Sacre-Coeur (Quebec, Canada) managed by Jean-Luc Malo is the World Investigation Centre for Occupational Asthmas (OA). Hence the interest raised by the author’s synthetic and retrospective study concerning his experience over the past 10 years (J.L.Malo et al Clinical & Experimental Allergy 2010 early on-line20 November) and concerning 665 investigations from which 519 patients are discussed in this highly documented report.

The authors first recall that the basic diagnosis factor is the reproduction of  bronchospasm, on work sites or in the lab, by inhaling the suspected causal substance, whether it be low molecular weight compounds, such as isocyanates for instance, or high molecular weight compounds, such as flours, cereals or a variety of allergens (animal hair, for instance). But this process is often risky for it is likely to trigger asthma exacerbation, even when using, as the Canadian authors did, safe new apparatus. That is why an attempt is being made to base the diagnosis on non-specific bronchial hyperresponsiveness (BHR) to methacholine associated with evidence of airway inflammation : sputum eosinophils and neutrophils, the sputum being either spontaneous or provoked before the challenge with the causal agent) as well as, in the case of allergens, skin prick-tests and serum specific IgEs.

Among the 519 subjects studied 2/3 were male, with an average age of 41.6 +/- 11.1 years. In 25% of them, 129, OA was confirmed ; in 187 (36%) OA was not confirmed ; in all others neither OA nor asthma could be identified. N.B. for 34 wheat flour-allergic subjects prick-tests and specific IgEs were assessed. Lastly, half the subjects were under corticoids. All these results were submitted to detailed statistical studies : bivariate analysis, logistic regression analysis, in order to identify the best predictive criteria.                                Results showed that BHR alone (PC20 : the metacholine concentration which lowers FEV1 by over 20%) is more often normal with OA than with non-OA : its positive predictive value (PP) is consequently low (35%). Coupling information on the level of eosinophils in sputum (1-3%), the PP rises to 69%.

With flour-allergic subjects, the triple association of PC20, eosinophils, and positive immunological tests, point to a very high probability of OA diagnosis. Therefore, wishing to avoid the risks of a direct provocation to the suspected occupational agent, the authors give us the best diagnosis criteria based on the OA-suspected subject’s triple status, i.e. functional tests, bronchial inflammation and immunological status.


3.    Alternaria asthma :

Theme : Asthma
Key words : Asthma, Alternaria, bronchial provocation test, skin prick-tests, specific IgEs

Asthma related to Alternaria sensitization (AA) has never enjoyed a great credibility among allergists, due partly to aerobiological and climatic differences between regions, partly to the rarity of the isolated sensitisation to this mould, and finally to the more or less reliable standardisation of extracts used for diagnosis. Hence, an article written by specialists from Madrid (C.Fernandez et al : Clinical & Experimental Allergy 2010 early on-line 20  November) brings a welcome scientific connotation.

The authors recall that the prevalence of this sensitisation varies from 3% in Portugal to 20% in Spain. They based their study and confirmed the diagnosis on the positive results of a bronchial specific challenge (BSC) carried out on 74 patients sent for asthma checks whose seasonal worsening of symptoms had evoked the possibility of a sensitisation to Alternaria. The BSC is described in detail and was conducted with the utmost precautions, monitoring the progressive FEV1 decrease in order to prevent any worsening of asthma. The retrospective study concerns 43 women and 31 men of 14-41 years of age, subject to moderate asthma ; 64 (86.5%) presented an allergy concomitant to that of Alternaria (57 to grass pollen, 29 to another mould , mainly Aspergillus, 25 to cats and dogs, 14 to dust mites). For A.alternata the results for 74 subjects were as follows : skin prick-tests (SPT) were positive in 47 subjects ; 26 negative SPT had a positive intradermal reaction (ID°) ; the specific IgEs were positive (9.6+/-17 kU/L) in 55 (in 21 cases the allergen recombining rAlt a 1 was used) ; the BSC was positive in 45 subjects (61%) with a dual reaction, immediate and delayed, in almost half the cases.

All these results were submitted to an close statistical analysis: Receiver Operating Curve (ROC) and logistic regression analysis (LR), with two main findings :

1)    SPTs almost certainly predict a BSC positive result (area under the ROC curve of 0.957) ; a negative SPT shows only a 4% probability of a positive BSC (LR), while ID° is only moderately efficient ; however a weal over 5.5mm in diameter had 90% probability of a positive BSC.

2)    Specific IgEs (CAP?16 kU) predict a positive BSC with 99% accuracy.
In conclusion, Alternaria-positive SPTs are sufficient to confirm diagnosis and BSC positivity. They make it possible to inform and treat of allergic subjects according to weather conditions. The authors even think that they can justify a possible immunotherapy with this mould.


4.    Attendance of day care centres and prevalence of childhood eczema

Theme : Atopia, skin allergies
Key words : Day care centre, attendance of day care centre, eczema

A group of German paediatricians and epidemiologists has just made a series of surprising observations : 10 years after reunification they observe, in a cohort of 3097 children followed from 1997 up to the age of 6, a distinctly higher prevalence of eczema in children living in East Germany compared to those living in West Germany (Cramer C. et al Allergy 2011 66 1 68-75).

They then attempted to explain the reasons for such a difference via a yearly questionnaire among the populations of the West (Munich and surroundings) and the East (Leipzig), searching for and quantifying a number of co-variables (over sixteen) likely to act as risk factors.

All the data underwent detailed statistical analysis.

First results confirmed a higher incidence and prevalence in children from the East than in children from the West, whether it be parent-reported or doctor-confirmed eczema, which cannot be accounted for by demographic or genetic factors (e.g. atopic family) nor by socio-economic factors or local traffic emissions or parental smoking, nor by breast feeding for the first 4 months, nor even by presence of allergens (cats or dogs) at home.

The only highly significant factor found is day care attendance during the first 2 years of life. Day care attendance was in fact more frequent in the East than in the West (here, in Leipzig more than in Munich).
The authors are all the more surprised since day cares centres are normally considered as a source of recurrent respiratory infections due to the promiscuity they create between attendants. And according to the “hygienic hypothesis”, this should have play a protective role against allergy. But it is the reverse which is observed here.

The authors evoke hypothetical emotional stress or more generally the role of psycho-neuro-immunologic factors that are sometimes found to be at the root of eczema.


5.    Indoor Air Quality (IAQ) and childhood asthma : variations between urban and rural areas

Theme : Asthma
Key words : Indoor air quality, indoor pollutants, allergic risk, urban dwelling, rural dwelling, Nitrogen Dioxide (NO2), aldehydes, BETEX (benzene, ethylbenzene, toluene, xylenes)

The harmful impact on respiratory health of indoor pollutants (IP) of urban dwellings (UD) are well known. On the other hand, epidemiologists evoke (cf. December 2010 BUA) the protective role of the rural dwelling (RD) against allergy and asthma. The French Clermont-Ferrand team of lung specialists (Prof. Caillaud) has attempted to compare the IAQ of both types of dwelling : urban and rural, in a clearly-delineated region, :  Auvergne, and to study the respective IP impact on childhood asthma (Hulin et al : Indoor Air 2010 Decembre  Vol 20 N°6  502-514).

Two groups of children aged 10-14 were the subject of this ‘case-control’ study: an urban group of 32 asthmatics and 31 controls belonging to the ISAAC cohort (French study of 6 major cities) and, in collaboration with the Auvergne Mutualite Sociale Agricole, a rural group of 24 asthmatics and 27 controls picked out of a school population in regular contact with farm animals (FERMA study).

The protocol prepared with the epidemiologists included, beside the dwelling characteristics (age of the buildings, thermal insulation, ventilation type), the quantification of the usual IPs in both types of dwellings by a 7-day continual assessment of NO2, PM2.5 particles, aldehydes (formaldehyde, acetaldehyde) and BETEX (benzene, ethylbenzene, toluene, xylenes), during summer and winter in the towns, summer only in the countryside. As to the demographic parameters (age, sex, family history of asthma or allergy, environmental smoking habits) these were established through medical examination, standard parental questionnaire and phone interviews. A thorough statistical analysis using several models made it possible to compare all the data between UD and RD and the respective health effects.

It appears that indoor pollution is twice as high in UD as in RD. Besides, in all the subjects tested, exposure to acetaldehyde and to toluene is significantly associated with a higher risk of asthma. Among children living in UD, that association is significant for toluene in winter and for BETEX with current asthmatics. With children living in RD, a significant relationship exists between formaldehyde and asthma levels.

Hence, daily exposure to even low concentrations of indoor pollutants can be implicated in  childhood asthma.

But what this study also reveals is that specific health effects of IP could occur in rural environments.


Source:  CEFCAP
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