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1. How should I treat adult patients with mild asthma in 2019
2. Mometasone or piotropium in mild asthma with low sputum eosinophil level
3. Budesonide - formoterol symbicort as needed for mild asthma
4. Wearable technology for air pollution
5. Maternal undernutrition and immune cell function reprogramed in offspring
In his updated guidelines (April 12 2019) the GINA (Global Initiative for Asthma) recommends that all patients aged 12 years and older should be treated with low dose inhaled corticoids, regularly or as needed, taken together with medication relaxing the bronchial muscle such short-acting SABA or long-acting β2 agonist. It appears that, in real-life adherence to so-called maintenance therapy is rather poor and the physician is confronted to many other phenotypes of mild asthma e.g. low or high levels of eosinophils in the sputum, intermittent or permanent episodes, with the risk of exacerbations. Two trials reported in the Journal analyses the best strategy in these different cases.Mometasone M or Tiotropium T in Mild Asthma with a Low Sputum Eosinophil Level
In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment was valuated in a 42-week, double-blind, crossover trial. 295 patients more than12 years of age were assigned to receive M (an inhaled glucocorticoid), T (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to M as compared with placebo and to T as compared with placebo among patients with a low sputum eosinophil level. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level (73%.)
Among these patients, there was no significant difference in the response to M or T, as compared with placebo. Among patients with a high eosinophil level, the clinical and functional response to M was significantly better than the response to placebo (74% vs. 26%) (which is not surprising) but the response to Tiotropium was not (57% vs. 43%). Then it is recommended in mild, persistent asthma with low eosinophils in sputum to use regular inhaled corticosteroids.Budesonide (B)- Formoterol(F) Symbicort® as needed for mild Asthma
Beasley, et al NEJM 2019 380 2020-2030
In previous double-blind, trials, budesonide–formoterol used on an as-needed basis, resulted in a lower risk of severe exacerbation of asthma, than as- needed use of a short-acting β2-agonist (Albuterol (A) but with less exposure to inhaled glucocorticoids. The New-Zealand authors of Wellington sought to confirm these findings in conducting a 52-week, randomized, open-label, parallel-group, controlled trial. 668 patients aged 18- 75 years were randomly assigned to one of three treatment groups:
- 226 A (100 μg, two inhalations);
- 227 to B (200 μg, twice daily) plus as-needed A;
- 222 BF (200 μg of B and 6 μg of F, (one inhalation) as needed.
The primary outcome was the annualized rate of asthma exacerbations. The results show that exacerbation rate in the BF group was lower than that in the A group and did not differ significantly from the rate in the B maintenance group.
D.Charpin Bulletin Acad Nle. Medecine 2019 in press
In France, monitoring of air quality is performed by approved organizations which use both measurements and modelisation. Alternatively, stationary cheaper apparatus and mobile microsensors which can be used by the general public have been marketed. Recently, Airparif has evaluated about one hundred microsensors in the lab and in real life conditions. In UK Airspeck has developed a mini censor which can be taped to an individual chest. The evaluation has turned on qualitative data such as energy source, reliability, changeability and usability and quantitative data such as measurement variability and systematic errors.
Besides these technical considerations, the question about possible behavioral changes induced by knowledge of air pollution data arises. This topic has been studied by ADEME in a 2017 report.
Its conclusion is that knowing air pollution levels and attached health impact does not by itself induce sustained behavioral changes. Those changes can only occur if they are easy to implement and if they are shared with other people. In the field of epidemiological research, microsensors will allow a more precise evaluation of individual exposure to air pollution. Maternal undernutrition and immune cell function reprogramed in offspring
Intrauterine undernutrition is closely correlated with higher risks of asthma in offspring. However, the underlying mechanisms of this susceptibility induced by intrauterine undernutrition is poorly understood. The Chinese authors from Shanghai, report in a well-established model of maternal protein restriction in mice, how in utero and in early life, immune cell functions are reprogramed as follows :
- Undernutrition in utero promotes CD4+ T-cell proliferation and TH2 skewing, leading to susceptibility to experimental asthma.
- Upregulated glycolysis is responsible for increased CD4+ T-cell proliferation and TH2 differentiation.
- The TH2 cytokine locus in naive CD4+ T cells is hypomethylated and induced by protein restriction diet in utero.
This confirms that asthma and allergic diseases have their origins in early life. After birth or during lactation, consumption of protein has no effect. these important findings underline the capacity of maternal diets to remodel cell-intrinsic metabolism and epigenetics within offspring immune cells, resulting in asthma susceptibility and offering new insights into the pathogenesis of other developmental origins of adult diseases.
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