February 2017

Claude Molina et Jacques Gayraud

1. Linking Air Pollution to Atopic Dermatitis
2. Skin Microbiome and Atopic Dermatitis                               
3. Guidelines about starting Inhaled Cortico-Steroids (ICS) treatment for mild Asthma                                          
4. Proton Pump Inhibitors in the treatment of Chronic Rhino-Sinusitis with nasal Polyps
5. Chronic Rhino-Sinusitis with Nasal Polyposis and Verapamil  

I. Linking Air Pollution (AP) to Atopic Dermatitis (AD)              
T.Hidaka et al Nature Immun2017January 18 64-76              
T.Hidaka et al : Nature Immunology 2017 18 64-73                       
AD is increasing worldwide in correlation with AP. The Japanese authors showed that organic components of pollutants activate the transcription factor AhR. Using AhR-CA mice that develop AD-like phenotypes, they identified Artn keratinocyte specific AhR target gene, whose product artemin is responsible for epidermal innervation that led to hypersensitivity, inflammation and pruritus. In patients with AD, AhR activation and expression of ARTN are positively correlated in epidermis. So AhR in keratinocytes senses environmental stimuli (B.Vaidyanathan et al J ; Exp.Med January 2017) and elicits AD pathology. These researches should be confirmed by epidemiologic studies

II. Skin Microbiome and Atopic Dermatitis                
E.A.Kennedy et al JACI 2017 January 139 1 166-172                   
The early origins of AD involve an interplay between the skin barrier, immune dysregulation and the skin microbiome. Staphylococcus aureus is often associated with flares of AD and it was not known whether this microbe precedes or follows the disease. The authors from Ireland and USA selected in the cohort of Cork, 10 babies and 10 randomly controlled infants with no AD and performed bacterial 16S sequencing and analysis directly from clinical samples at 3 points in the first 6 months of life and at 4 sites (antecubital and popliteal fossae, nasal tip and cheek) relevant to AD. They were able to show that S. aureus did not precede the development of AD and surprisingly   several commensal staphylococci present at 2 months were associated with reduced incidence of AD at 12 months suggesting that this genus might be protective and anti-inflammatory.

III. Guidelines about starting Inhaled Cortico-Steroids (ICS) treatment for mild Asthma                                         
H.K.Redell et al Lancet 2017 January 389 1066 157-166,          
These Australian authors aimed to assess the validity of classical guidelines for starting ICS only in asthma with symptoms more than 2 days per week. They perform a post-hoc analysis of the 3years study done in 32 countries with clinic visits every 3 months in patients identified by baseline symptom frequency.                                
7138 patients were investigated:
§  3577 received once daily inhaled Budesonide 400µg (200 for those aged
§  grouped by more than 2 symptoms days/week or fewer (divided in 2 subgroups : no day to one day, and more than 1 day to 2 days)
Coprimary outcomes were time to first severe asthma event and change in baseline lung after bronchodilator function.              
Analysis reveals that time to first severe event was significantly longer across frequency subgroups, for Budesonide versus placebo; similar results were noted for lung function which was higher at 3 years, in the low frequency subgroups.                                     
In conclusion in mild recent-onset asthma once daily low dose Budesonide decreases the risk of severe event-related-asthma, reduces lung function decline and improves symptoms control similarly in all subgroups. These results do not support restriction of ICS to patients with symptoms on more than 2 days per week.

IV. Proton Pump Inhibitors in the treatment of Chronic Rhino-Sinusitis with nasal Polyps :
J.Y.Min et al JACI 2017 January 139 1 130-141                   
Recent findings suggesting that PPI may modulate expression of eotaxin 3, an eosinophil chemo-attractant, the American and Japanese authors aimed to assess their therapeutic potential in CRSP characterized by tissue eosinophilia and the role of IL 13 , cytokine of Th2 nasal inflammation.                           
Nasal tissues and secretions were measured by multiplex immunoassay and showed increased IL13 and eotaxin 2 and 3 levels correlated with clinical and radiologic scores of severity. Moreover patients taking PPI had significantly lower levels in vivo eotaxin levels compared with those without PPI. Underlying mechanism reveals that PPI reduce IL13 induced eotaxin 3 expression by non-gastric H-K ATPase, (encoded by a different gene) necessary for IL 13 mediated-epithelial response.

V. Chronic Rhino-Sinusitis with Nasal Polyposis and Verapamil  
M.M.Miyake et al JACI 2017 2 Article in press
Epithelial P-Glycoprotein (P-gp) is a membrane efflux pump that is overexpressed in CRSwNP and regulate the secretion of Th2 polarizing cytokines. This double blind placebo-control randomized clinical trial of Verapamil® first generation calcic inhibitor and also inhibitor of P-gp, capable of blocking Il5 and IL6, showed that V (80 mg 3 times a day) improve significantly the clinical and radiological scores of treated patients compared with Placebo. However the results are not significant in patients with increased BMI and those with elevated P-gp at baseline. Given that V is cardioactive the risk of high doses limit its use, but monotherapy at low doses is well tolerated, with less side-effects and lower costs. These findings open the door to future researches with calcic inhibitors of new generations.

Your comments and questions are welcome at the following addresses:

Claude Molina                             

Jacques Gayraud