Bibliographic updates

The Monthly choice - January 2016

Claude MOLINA* & Jacques GAYRAUD**

1.    Obesity and Asthma in children
2.    Blood eosinophil  count as therapeutic guide in Asthma
3.    Th2 immunity in atopic children : dissociation between sensitization  and symptomatic allergic symptoms     
4.    Management of chronic refractory cough

1. Obesity and Asthma in Children
A.Charles et B.Heude : Bulletin de l’Académie de Medecine 2015 (sous presse)    
H Graseman .Mol.Cell.Pediatr 2015 Dec  2(1)6 doi.  

According to WHO, 42 million children under age of 5 were obese or overweight in 2013 and the prevalence has dramatically increased in the second half of the 20th century. Many factors interfere with early development, from the prenatal period, where the main factor is the maternal BMI before pregnancy, to the  post-natal period : e.g. the first 2 years of life,  where maternal and infant weight gain, smoking during pregnancy, caesarean delivery, are important risk markers. Moreover advances in genetics and in intestinal microbiota should help to understand the mechanisms of this obesity and the susceptibility to association with Asthma , Eczema and other non- communicable diseases such diabetes.

As for Asthma, the relationship remains controversial. The clinical presentation is distinct from other Asthma phenotypes and depending on age of onset of symptoms. More frequent in girls, it tends to be more severe, not typically associated with allergy, and less responsive to standard anti-inflammatory therapy, including inhaled corticosteroids and β2 agonists. Obesity may lead to Asthma via a number of mechanisms including changes in lung mechanics, the nitric oxide metabolism, and by causing inflammation. Conversely poorly controlled Asthma may precede Obesity which is favored by sedentarity and intensified treatment with systemic corticoids. Anyway all supportive interventions should include weight loss.

2. Blood eosinophil  count as therapeutic guide in Asthma (A)
D.B.Price et al
Lancet Respiratory Med 2015  3  849-858      

The authors investigated, in a large UK cohort of asthmatics, aged 12-80 years, with 2 years of continuous records,  the relation between a blood eosinophil definite count of 400cells/µL and prospective annual A. outcomes.            
-    20 929(16%) of 130 248 patients had a count greater, during the outcome year, and they, significantly, experienced more severe exacerbations and acute events than those with a count less. They had also lower odds of achieving A. control, defined as limited reliever use and no asthma-related hospital admission or course of oral corticosteroids.                                                          
-    Moreover exacerbation rates increased progressively with 9 ascending categories of blood eosinophil count as compared with a reference of 200 cells /µ/L or less.

In conclusion, blood eosinophil count, greater than 400cells /µL, easier  to practice in primary care, than sputum count, is a good predictor of  Asthma exacerbations. In these patients who have poorer asthma control the eosinophil count which is in relation with outcomes may act as a guide for an efficient therapy

3. Th2 immunity in atopic children: dissociation between sensitization  and symptomatic allergic symptoms
P.Holt et al 
JACI décember 2015 In press

Among children with asthma and rhinitis, sensitized to aero-allergens, mainly HDM and grass, only a minority are symptomatic, implying a mechanism of anti-inflammatory control,attenuating expression of IgE responsiveness to allergens.

The authors analyzed  in 3 independent populations (Australia, UK, Sweden) relationships between allergen specific IgE and corresponding specific IgG,   and associated immunophenotypes.

Depending on age/allergen specificity 20% to 40% of children with sIgE of 35kU/L or greater in the serum, had negative skin tests  and  a high ratio of IgG/IgE.
IgG1  (not IgG4) from these children inhibited basophil activation in a dose –dependent fashion and  are associated to a strong IL 10-dependent gene signature. Among non symptomatic there was also a significant higher IL 10/Th2 cytokine (protein) ratio.

Conclusion , IL 10 might have a dual function of  attenuating effector  activation of late phase allergic response and promoting IgG 1, which  modulates the  acute phase reaction. This sIgG 1/ sIgE balance represents an accessible  therapeutic target for asthma and rhinitis control.
4. Management of chronic refractory cough (CRC)
P.G Gibson et al
BMJ  2015  Décember 14  and Chest 2015 1496
Defined as a cough that persists despite guideline base treatment, more than 8 weeks,  CRC also described as unexplained cough or cough  hypersensitivity syndrome, has a substantial impact on quality of life. Seen in adults, the symptoms include dry irritation around the laryngeal region, sometimes globus, dyspnea or dysphonia. 11 Randomized  control clinical trial and 5 systematic review edited guidelines.
-    Its pathophysiology is complex including reflex sensitivity, central and peripheral sensitization.
-    Several treatments has been developed over the past decade such speech pathology interventions, use of neuro-modulators such as gabapentine and pregabalin.
-    Potential novel treatment with  AF 219 an oral purinergic receptor antagonists (in airways afferent vagal nerves ) was associated  with a  significant 75% reduction in cough frequency (Lancet 2015 385 1198-2005) 

Comments and remarks may be sent to:
Claude Molina                    
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Jacques Gayraud
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Last updated 21 November 2016