Claude MOLINA and Franz MARRACHE

•    Lifetime risk of developing asthma
•    Bronchial thermoplasty (BT) : a recurring issue
•    Indoor fungal concentration, Allergy and Asthma
•    Floor vacuum cleaners and Allergy in young children
•    Combination therapy: Inhaled Corticosteroids/Long acting β2 agonists: Molecular mechanisms and evaluation in asthmatic children

Lifetime risk of developing asthma

What is the risk of becoming asthmatic from birth to age 79 years?
The Public Health Authorities of Toronto, Canada, has tried to answer this question, recording of individuals living in Ontario and who were not asthmatic in 1996, and were followed up for 11 years (for some of them, until they were 80 years old or died). Those who have been physician diagnosed with Asthma, either due to hospitalisation or 2 consecutive appointments to the physician in a period of 2 years (mentioned in Social Security databases) were censored
More than 9 million individuals were recorded (49% males; 84% living in an urban environment), and 5.9% cases of asthma were reported. These were more frequent in subjects aged between 0 and 9 years and less frequent in adults between 60 and 69 years of age. The analysis technique used was similar to that of survival statistics.
Taking into account all confounding factors, the cumulative risk observed was 33.9%, which seems high for a developed country.
The authors stratified the results according to gender, age, urban or rural environment, social class and income. The highest risk was observed in the female sex except in the first years of childhood during which the risk was higher in males. It was also higher in the urban environment and in the suburbs as well as in low income families.
Over all, it seems that in Ontario, 1 individual out of every 3 has a risk of becoming asthmatic in his life, which is similar to the figures observed with chronic diseases such as diabetes, cancer or Alzheimer’s disease.
Asthma is thus clearly the most frequent respiratory illness in Canada (T. To et al. Am. J. Respir. Crit. Care Med. 2009 ; ahead of print, November 19) and its economic repercussions are important.
This conclusion should be taken into account by Officials in charge of Public Health in all countries, at a time of questions on world climatic and environmental changes seem to be a hot topic.

Bronchial Thermoplasty (BT) : a recurring issue

We have addressed this issue several times in our BUA in 2006 and 2007 :
(Cox et al. Am. J. Respir. Crit. Care Med. 2006 ; 173 : 965-969 and N. Engl. J. Med. 2007 ; 356 : 1327-1337 ; J. Solway et al. 1367-1369).

Recently, M. Castro et al. (Am. J. Respir. Crit. Care Med. 2009 ; October 8 : 1-26) published the results of a multicentre study involving 297 patients, with a strict, randomised, blind methodology  including an active group (AG) and a control group (CG), and  bronchoscopy performed in both groups, with airways warming only applied to AG.
This study confirmed the reproducibility of results already obtained by this technique.
Pointed out to severe asthma resistant to currently drug therapy, BT showed its efficacy after periods of 3, 6 or 12 months, as reflected in a significant improvement of the Asthma Control Questionnaire score (assessing the quality of life of the asthmatic patient)
Likewise a decrease in the rate of exacerbations, in the number of medical appointments, medical department visits, and hospitalisations were observed.
By contrast, the authors did not show any difference between the 2 groups in terms of FEV1 or  level of bronchial reactivity.
BT, as in previous studies, was followed by a short term worsening of the respiratory status with an increase in cough, dyspnoea, fever and mucous secretion.
The high cost of repetitive sessions adds to the burden of this technique which induces immediate not negligible side effects, has an uncertain mechanism of action, except for the reduction of the contractile smooth muscle mass.
This highlights the need to look for a less invasive medical or  molecular treatment, which may be able to targeting the bronchial smooth muscle.

Indoor Fungal concentration, Allergy and Asthma

Two recent reports have again emphasized the relationship between fungi and Allergy or Asthma.
One of these studies was carried out in the East of France, at Besancon (G. Reboux. Indoor Air 2009 ; 19 : 446-453) and  analysed fungal contamination in 118 dwellings ; 32 were unhealthy (visible contamination and health outcomes reported by the occupants), 27 were inhabited by allergic patients (as confirmed by skin prick testing) and 59 matched controls. This research was performed during 3 months, avoiding the Summer season, and showed  good reproducibility.
Unhealthy dwellings had higher airborne concentrations (as estimated by impaction method) of Aspergillus, Penicillium and Cladosporium than control homes; and their bedroom walls were clearly more contaminated .
The homes of allergic patients were different from those of controls since they only had a higher airborne concentration of Penicillium and their bathroom walls were more highly contaminated than others.
The quantitative thresholds of airborne concentrations spread out  between 170 and 1000 CFU (Colony Forming Units) , the latter being considered as a potential health hazard . Moreover according to the authors, qualitative assessment also requires collection of samples from contaminated surfaces.
Finally, molecular identification of the 12 species of Penicillium observed showed a preponderance of P. Chrysogenum and Olsonii. This underlines the biodiversity of the fungi and the need to have adequate extracts for skin prick testing which are in agreement with the patient environment.

The 2nd study compared skin tests with allergen-specific serum IgE , for the diagnosis of fungal sensitisation in 121 cases of severe Asthma (B. R. O’Driscoll et al. Clin. Exp. Allergy 2009 ; 39 : 1677-1683) After testing patients with 6 different fungi (Aspergillus, Candida, Penicillium notatum, Cladosporium herbarium, Alternaria alternata and Botrytis cineria), as well as analysing Trichophyton-specific IgE serum levels, the authors of Manchester (United kingdom) concluded that these two tests are required to ensure the diagnosis which leads to an adequate anti-fungal treatment.

Floor Vacuum Cleaners and Allergy in young asthmatics:

Vacuum cleaners are usually recommended to reduce environmental allergens levels and improve symptoms of Asthma and Rhinitis. However, some other studies have challenged this assumption and suggested that they increase allergens load in homes.
A group from Singapore (G.C. H. Koh et al. Indoor Air 2009 ; 19 : 468-473) recruited 102 physician diagnosed allergic asthmatic patients whose mean age was 12 years. The study compared  methods and frequency of floor cleaning (vacuum cleaning, sweeping or humid mop) with sensitisation to house dust mites and cockroaches,  ECP levels (as biomarker of atopy), and  inhaled corticosteroid use in patients with allergic rhinitis.

Statistical analysis showed that individuals using vacuum cleaning had a significantly higher degree of sensitisation to 3 varieties of house dust mites (Dermatophagoides pteronyssinus, D. farinae and Blomia tropicalis) but not to cockroaches (Blatella Germanica and Periplanata americana). These individuals also had higher serum levels of ECP, in comparison with those using other methods of cleaning.

Different hypotheses were put forward to account for this paradoxical phenomenon: Scattering of house dust due to its handling and emptying  reservoir bags which may have varying degrees of air tightness; Lack of efficiency of vacuum cleaning devices some of which were old or did not have expensive HEPA  (high efficiency particle arrestor)  or Persistence in air, in spite of vacuum cleaners, of small particles (1.1 to 4.7µ), supposed to carry house dust mite allergens (cockroach allergens are carried by larger particles).

Finally, the authors recognize that these observations made in a humid tropical climate may not necessarily apply to a temperate one.

Combination therapy :Inhaled Corticosteroids (CS)/Long acting β2 agonists (LABA) Molecular mechanisms and evaluation in asthmatic children

Recent pharmacological and molecular studies have described the complex mechanism underlying the beneficial synergy of a joint use of these 2 major  drugs classes in asthmatic patients (Judith Black et al. Chest 2009 ; 136 : 1095-1100). In this excellent work, the authors studied, at first in vitro, the mode of action of each of these 2 drugs:
- LABA stimulate the Glucocorticoid Receptor (GR), inducing its translocation into the nucleus resulting in increase of genetic transcription induced by CS. In bronchial smooth muscle cells and fibroblasts, there is formation of a complex with another transcription factor - C/EBP-α., This complex is absent in asthmatic patients, which may explain that CS do not inhibit the proliferation of these cells .
Furthermore, LABA act upon mast cells, decreasing release of inflammatory mediators and deposition by fibroblasts of extracellular matrix proteins which are responsible for bronchial remodelling.
However, repetitive stimulation leads to a well known form of «desensitisation» : lack of efficacy of LABA, a phenomenon which is inhibited by CS.
- CS modulate and increase transcription of different genes namely those of β2. These drugs have a classical anti-inflammatory action, but cannot, by themselves, avoid proliferation of smooth muscle cells and thickening of bronchial wall.
- In vivo, the combination of these 2 drugs, leads to an increase in the translocation of the GR towards the nucleus, a decrease in inflammatory mediators and an increase in the number of β2 receptors ;

This is the reason why joint products were developed, with fixed doses of each of these 2 drugs, which allows, with a single inhaler and a single daily administration, saving of corticosteroid doses and achieving a higher level of adhesion to treatment. This is the case of the associations : Formoterol/Budesonide   (Symbicort®), Salmeterol/Fluticasone (Seretide®) ,Formoterol/Beclomethasone (Innovair®).

A recent confirmation has been reported by the french-polish-russian-danish, double blind, multicentre study (De Blic et al. Pediatr. Allergy Immunol. 2009 ; 20 8 : 763-771) carried out in asthmatic children, which showed beneficial effect of  Salmeterol/Fluticasone association in comparison with isolated Fluticasone.


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