Tabac et maladies inflammatoires de l`intestin

Tabagisme et maladies inflammatoires intestinales
Edouard Louis
Increasing incidence of IBD
Différentes facettes des MICI
Cancer colo‐rectal
Sténoses intestinales
Abcès et fistules
Mesalazine
Immunosuppresseurs
Corticoïdes
Antibiotiques
Anti‐TNF
Fractures sur
ostéoporose
Bactéries‐virus‐flore
Germes spécifiques ?
Rupture de tolérance ?
Déficit de défense primaire non spécifique?
Variations génétiques majeures détectées par GWAs dans les MICI
Chr Gène
Fonction CD UC
1p31
IL‐23 receptor
Immune inflammatory response
+
+
5q33
IL‐12b (p40)
Immune inflammatory response
+
+
9p24
JAK2 Signaling molecules
+
+
17q21
STAT3 Transcription factor
+
+
18p11
PTPN2 T cell tyrosine phosphatase
+
‐
9q32
TNFS15
Immune inflammatory response
+
‐
6q27
CCR6 Chemokine receptor
+
‐
3p21
MST1 Macrophage chemotaxis
+
‐
2q37
5q33
ATG16L1
IRGM
+
+
‐
‐
16q12
NOD2/CARD15 Bacterial recognition
+
‐
20q13
TNFRSF6B Inflammatory response, apoptosis
+
+
12q12
PSMG1
PTGER4 MUC19
1q32
IL‐10
21q22
5p13
Autophagosome pathway
Autophagosome pathway
Proteasome‐related protein
+
+
Barrier function, immunoregulation + ‐
Epithelial integrity
‐
+
Immunoregulation
‐
+
Tabagisme
Augmente le risque de MC
Augmente l ’agressivité de MC
Inverse dans RCUH
Mécanisme ?
Mucus, flore, IgA secrétoires, vascularisation
Probability of flare‐up
Probability of
flare‐up (%)
100
21
60
14
40
35
17
20
0
Probability of
steroid course (%)
6
p <0.001
80
37
0
12
24
48
Months after inclusion
Probability of steroid course
100
80
40
28
20
38
12
80
p <0.001
60
15
40
36
20
0
40
0
12
42 24
21
18
36
Quitters
Continuing smokers
Non‐smokers
20
19
39
0
Probability of starting
or changed IS therapy
100
Months after inclusion
10
p <0.001
60
0
36
Probability of starting
or changed immuno‐
suppressive therapy (%)
Impact of smoking cessation in CD Optimising disease control
24
36
Months after inclusion
48
Cosnes J, et al Gastroenterol 2001; 120:1093
48
Effet du tabagisme sur les MICI
Mécanisme de l’impact du tabac sur les MICI
Choix Cornélien dans la RCUH
• EM née en 1955
• RCUH sous forme de colite gauche depuis 1992 (arrêt du tabagisme en 1990)
• Traitement par mesalazine efficace et rares cures de corticoïdes jusqu’en 2003
• Développement d’une corticodépendance requérant un traitement par azathioprine
• Efficacité transitoire avec épargne cortisonique jusqu’en 2005, puis échappement thérapeutique
• Options: colectomie totale vs anti‐TNF (encore expérimental à l’époque)
To smoke or not to smoke…
• Reprise du tabagisme (10 cigarettes/j) par la patiente et entrée en rémission maintenue par la mesalazine seule
• Octobre 2011: apparition d’un cancer pulmonaire
Arrêt du tabac dans la maladie de Crohn: un objectif difficile
• 474 consecutive smokers with Crohn's disease – Repeated counseling to stop smoking, with easy access to a smoking cessation program – Patients who stopped smoking for more than 1 year (quitters) were included in a prospective follow‐up study, which compared disease course and therapeutic needs with 2 control groups, continuing smokers and nonsmokers
• There were 59 quitters (12%) – Predictors of quitting were the physician, previous intestinal surgery, high socioeconomic status, and in women, oral contraceptive use. – During a median follow‐up of 29 months (1‐54 months), the risk of flare‐up in quitters did not differ from that in nonsmokers and was less than in continuing smokers (P < 0.001). Gastroenterology. 2001 Apr;120(5):1093‐9.
Smoking cessation and the course of Crohn's disease: an intervention study.
Cosnes J, Beaugerie L, Carbonnel F, Gendre JP.
L’arrêt total du tabagisme est nécessaire
• 2795 consecutive patients during the period 1995‐2007
– Patients were classified as nonsmokers (n = 1420), light smokers (1‐10 cigarettes/day; n = 385), heavy smokers (>10 cigarettes/day; n = 638), and intermittent smokers (change in smoking habits; n = 352). – Course of the disease expressed as patient‐years while smoking were compared to patient‐years without smoking. • The percentage of years with active disease was 37% in nonsmokers versus 46% in light smokers (P < 0.001; adjusted hazard ratio 1.30 [1.19‐1.43]) and 48% in heavy smokers (P < 0.001; adjusted hazard ratio 1.68 [1.57‐1.81]), despite an increased use of immunosuppressants in smokers.
• Hospitalization rates were also increased in both groups of smokers, with 12% in nonsmokers versus 15% in both groups of smokers (P < 0.001 for both comparisons). Inflamm Bowel Dis. 2009 May;15(5):734‐41.
Effects of light smoking consumption on the clinical course of Crohn's disease.
Seksik P, Nion‐Larmurier I, Sokol H, Beaugerie L, Cosnes J.
Improving patients’ empowerment by motivational interviewing
Motivational interviewing is a patient‐centered,
directive method for enhancing intrinsic motivation to change
by exploring and resolving ambivalence
William R. Miller et Stephen Rollnick
No Change
Change
What are the main differences between conventional and motivational interviewing?
Motivational
Conventional
•
•
•
•
•
•
Argues that the patient has a problem and needs to change
Offers direct advice or prescribes solutions to the problem without the patient’s permission or without actively encouraging the patient to make his/her own choices
Uses an authoritative/expert stance, leaving the patient in a passive role
Does most of the talking, or functions as a unidirectional information‐delivery system
Imposes a diagnostic label
Behaves in a punitive or coercive manner
•
•
•
•
•
Seeking to understand the patient’s frame of reference, particularly through reflective listening
Expressing acceptance and affirmation
Eliciting and selectively reinforcing the patient’s own self‐motivational statements, expressions of problem recognition, concerns, desire and intention to change, and ability to change
Monitoring the patient’s degree of readiness to change, and ensuring that resistance is not generated by jumping ahead of the patient
Affirming the patient’s freedom of choice and self‐direction
Conclusions
• Le tabagisme est le facteur environnemental dont l’impact sur les MICI est le mieux documenté
• L’impact différent sur le Crohn et la RCUH est intriguant et incomplètement compris
• Le clinicien est parfois confronté à un choix cornélien dans la RCUH
• Plus d’énergie, de moyens et de motivation devraient être mis pour l’arrêt du tabagisme dans le Crohn