Totul despre relatia

Fumat-BPOC
Antigona Trofor
Clinica Pneumologica Iasi

Sumar
Aspecte generale
Caracteristici particulare ale BPOC la fumtori
Beneficiul renunrii la fumat n BPOC
Intervenii terapeutice recomandate
De ce pacienii cu BPOC renun mai greu la fumat?
Concluzii

Cifrele vorbesc *

Fumatul este principala cauz evitabil de moarte

BPOC a 5-a cauz de mortalitate pe glob
Fumatul principala cauz de BPOC (RR-13)
Pn la 50% din fumtorii cronici dezvolt BPOC
80-90% din mortalitatea prin BPOC se datoreaz
fumatului
i fumatul pasiv este o cauz a BPOC ( n Germania
-900 de nefumtori mor anual, din 27% expui n
populaia general)
* Andreas S., Hering T., Muhlig S., Nowak D., Raupach T., Worth H., Smoking Cessation in COPD- a
Clinical Practice Guideline, Dtzch. Arzetbl. Int. 2009, 106 (16), 276-82

Intervenia este obligatorie

Fumul de tutun aerosol toxic cu implicaii
multiple respiratorii
BPOC este o boal sistemic
Marea majoritate (80%) a fumtorilor ar vrea s
renune n principiu, ns doar 30% au cel puin
o tentativ n utimele 12 luni
Tentativa de renunare neasistat are succes n
doar 5%

Worldwide, the most commonly encountered risk factor

for COPD is cigarette smoking. At every possible
opportunity individuals who smoke should be
encouraged to quit.

GOLD 2008

Un singur pacient dou boli

Dependena nicotinic
Boala cronic recidivantF17.2
Dependena fizico-psihocomportamental
Simptome de sevraj
Efecte sistemice ale
fumatului: inflamaie,
stress oxidativ la nivelul
funciei endoteliale i
vasomotorii

BPOC
Boala sistemic cu
manifestri respiratorii i
extrarespiratorii:
cardiace, musculare,
psihice, nutriionale,
sociale, etc.
n formele severe:
dependena de oxigen/de
ngrijirile medicale

Smoking
Epithelial cell
& PM10

Local
Inflammatory
response

IL-8

PMN

cytokines
IL-6, IL-1
GM-CSF, IL-6

Systemic
Inflammatory
response

IL-1
TNF-

BONE MARROW

LIVER

Leukocytes and platelets

Active phase
proteins

Endotelial activation

Vascular disease
Van Eeden SF et al. Proc Am Thorac Soc 2005;2:61

Air Trapping Links Pathophysiology and

Patient-Centered Outcomes in COPD
COPD
Hypoxemia

Airflow Obstruction

Exacerbations

Ventilatory
Requirement

Tachypnea

Air Trapping
Anxiety

Deconditioning

Hyperinflation

Dyspnea
Patient-Centered
Outcomes

Activity
Limitation

Poor Health-Related Quality of Life

Cooper. Am J Med. 2006;119(10A):S21-S31.

Inflammatory Mechanisms in COPD

Cigarette Smoke
and Other
Irritants
MCP-1

Epithelial Cells

Alveolar
Macrophage

Neutrophil Chemotactic Factors

Interleukin-8, Leukotriene B44

Neutrophil

CD8+ T Lymphocytes
Alveolar-Wall
Destruction
(Emphysema)

Protease
Inhibitors

Proteases

Neutrophil Elastase
Cathepsins
Matrix Metalloproteinases
Mucus Hypersecretion
(Chronic Bronchitis)

MCP-1=monocyte chemotactic protein-1.

Adapted from Barnes. Curr Opin Pharmacol. 2004;4(3):265; Celli et al. Eur Respir J.
2004;23:932-946.

COPD: Pulmonary Inflammatory

Response
Normal lung functionb

Severe emphysemab
Inflammatory Cells

Inflammatory Cells

a
a
a

12

0 10 ,
1
,
,
, 8
N 2 ro
,
4 CD
1
c
s
PM 10Ma 12Eo CD
0

12

0
1

,
0
2 12
D
C 10

0
1

12

1
0
,
0
1
1

,
N, 2 cro 2 s,

0
,
,
1
a
M
2 12
4
8
P 10 M 01 Eo
D
D
D
C 10
C
C

CD4=T lymphocyte; CD8=T lymphocyte; CD20=B lymphocyte; Eos=eosinophils; Macro=macrophages;

PMN=polymorphonuclear. aP<.01 from control and mild. bLung tissue from respective patients was obtained
following lung resection.
Retamales et al. Am J Respir Crit Care Med. 2001;164(3):469-473.

Oxidative Stress in COPD

Cigarette Smoke
Inflammatory Cells
(Neutrophils,
Macrophages)

Decrease in Antiproteases
11-Antitrypsin and Secretory
Leukoprotease Inhibitor

Activation of
Nuclear Factor-B

Tumor
Necrosis
Factor-

Neutrophil
Recruitment

O2, H2O2
OH, ONOO

Increased Mucus
Secretion

Interleukin-8

Bronchoconstriction
Plasma Leak

lsoprostanes

Barnes. Curr Opin Pharmacol. 2004;4:265; GOLD Initiative 2006. http://www.goldcopd.com.

Accessed
July 23, 2007.

Ce este diferit la fumtorii cu

BPOC vs cei non BPOC?
Fumeaz mai mult
Au o dependen nicotinic mai sever
Sunt mai deprimai
Sunt mai puin dispui s ncerce s renune la fumat
Au nivele mai ridicate ale monoxidului de carbon n aerul
expirat

Differential characteristics of smokers with

COPD vs those without

Spain a general population study

1023 active smokers, 15% of cases
with COPD by spirometry.

Jimenez-Ruiz CA, Masa F, Miravitlles M, et al.

Smoking characteristics:differences in attitudes and
dependence between healthy smokers and smokers
with COPD. Chest 2001;119:1365-70

Poland 4494 smokers

(age 40+, smoking >10 pck/y) .
1177 (26,2%) had airways obstruction

Bednarek M, Gorecka D, Wielgomas J, et al. Smokers

witth airway obstruction are more likely to quit
smoking. Thorax 2006;61:869-73.

De ce este benefic renunarea

la fumat n relaia cu BPOC?
Previne dezvoltarea BPOC
Previne progresia BPOC: ameliorarea simptomelor,
mbuntirea funciei pulmonare, reducerea
exacerbrilor.
Crete eficacitatea medicaiei bronhodilatatoare i a
oxigenoterapiei
Scade mortalitatea

Smoking Cessation: Improvement in

Postbronchodilator FEV1 Decline
Susceptible smokers develop significant lung function decline

Postbronchodilator FEV1 L

Sustained Quitters
Continuous Smokers

2.9
2.8
2.7
2.6
2.5
2.4
Screen 2

Follow up (y)
Anthonisen et al. JAMA. 1994;272(19):1497-1505; Kanner et al. Am J Med. 1999;106(4):410-416.

Renunarea la fumat: inflamaia

aerian i BPOC
Date* despre evaluarea efectului renunrii la fumat la
fumtorii cu BPOC vs. fumtori cu funcie pulmonar normal
pledeaz pentru meninerea inflamaiei aeriene la ex-fumtori
Chiar i dup ce opresc fumatul, candidaii la BPOC
nregistreaz o inflamaie aerian persistent i creterea
celulelor inflamatorii din sput
Inflamaia persistent observat la pacienii cu BPOC se
datoreaz refacerii tisulare de la nivelul cilor aeriene
Fumtorii asimptomatici au fie un nivel constant, fie o
reducere semnificativ a celulelor inflamatorii din sput
Willemse et al. Eur Resp J. 2005;26(5):835-845.

Terapii de renunare la fumat n

BPOC
Consiliere
Terapie farmacologic: TSN, bupropion, vareniclin
Suport psihologic
Terapie comportamental
Materiale informative ajuttoare

Abstinence rates, relative risk and risk differences for the

combination of a behavioural intervention and
pharmacotherapy (NRT) compared with no intervention
Study

Treatment Control
n/N
n/N

Rd (fixed)
95% Cl

RD (fixed)
95% Cl

Point prevalence abstinence at 12 months

Anthonisen SI-P vs. UC

674/1962

177/1964

0.25 [0.23, 0.28]

Anthonisen SH vs. UC

680/1961

177/1964

0.26 [0.23, 0.28]

Prolonged abstinence after 5 years

Anthonisen SI-P vs. UC

427/1961

102/1964

0.17 [0.15, 0.19]

Anthonisen SI-P vs. UC

408/1961

102/1964

0.16 [0.14, 0.18]

-0.25
FAVOURS CONTROL

0.25
FAVOURS TREATMENT

Wagena EJ, van der Meer, Ostelo RJWG, et al. The efficacy of smoking cessation strategies in people with
chronic obstructive pulmonary disease: results from a systematic review. Respir Med. 2004;98:805-15

+ B SR

+ NRT

nicotine gum vs 1964 no intervention

Christenhusz study 225 COPD pts allocated to minimal
intervention vs group therapy + bupropion
12 mo abstinence rate

Effects of behavioural smoking

cessation intervention (+Tx) in
COPD
LHS 3923 smokers allocated to group therapy +

Tashkin DP, Murray RP. Smoking cessation in chronic obstructive pulmonary 2009;103,
963-974

TSN *
O rat de succes la 12 luni mai mic: ( 8.7%
plasturi 15 mg, 5.1% inhaler, 3.5% inhaler+
plasturi 15 mg) comparativ cu fumtorii sntoi
Rata similar cu a fumtorilor sntoi: 23 %
tableta sublingual vs 10% placebo
Lung Health Study: rata abstinenei pe termen
lung a crescut simitor: 39 % n grupul de
intervenie vs 22%.
* Tonnesen et. al. ERJ 2007, vol 29, nr.2, p.390-417

Abstinence rates, relative risk and risk

differences for bupropion compared with
placebo in COPD
Study

Treatment Control
n/N
n/N

Rd (fixed)
95% Cl

RD (fixed)
95% Cl

Prolonged abstinence after 6 months

Tashkin 2001

32/204

18/200

0.07 [0.00, 013]

Prolonged abstinence after 12 months

Tashkin 2001

21/204

17/200

-0.25

PAVOURS CONTROL

0.02 [-0.04, 007]

0.25

PAVOURS TREATMENT

Wagena EJ, van der Meer, Ostelo RJWG, et al. The efficacy of smoking cessation strategies in people with
chronic obstructive pulmonary disease: results from a systematic review. Respir Med. 2004;98:805-15

Bupropion *
Metaanaliza a 19 studii: odds ratio de 2,06
n favoarea bupropion SR vs. placebo
712 sptmni + consiliere
Tashkin i col: pn la 14% rata de sevraj
Bine tolerat, n privina riscului de HTA
Repetarea curei crete rata de succes
*

Tonnesen et. al. ERJ 2007, vol 29, nr.2, p.390-417

Vareniclina n BPOC *
Eficacitatea superioar n spt. 9-12
(43.3% vs 8.8% la grupul placebo)
Eficacitate mai mare n follow-up
(spt.9-52: 18.6% vs 5.6% la grupul placebo)
Efecte adverse: 2.8% grup vareniclina vs 4.4%
grup placebo
*Tashkin D. et. al, Efficacy and safety of varenicline for smoking
cessation in mild to moderate COPD, 2009.

Tabel 1 Caracteristici demografice

Vareniclina n BPOC

Date de cost eficienta*

Renunarea la fumat este cost-eficiena n tratamentul
BPOC
Costul sevrajului: 1117 vs. 99 000 cost
economisit/an de viaa de calitate la un pacient cu
BPOC! ( revizuirea a 12 studii 1994-2007)

* Smoking cessation compared to treatment of COPD and other smoking-related diseases using cost-effectiveness
evidence
Jens Dollerup1, Peter Bo Poulsen1, Hans-Jacob Randskov HJ1, Kjeld Mller Pedersen2
1. Pfizer Denmark, Ballerup, Denmark
2. University of Southern Denmark, Inst. of Public Health, Odense, Denmark
E-communication 4647

aproape totul.
BPOC

Femeile fumtoaremai susceptibile *

Fumtori vs.
nefumtori
Iniiat de fumat pasiv
n copilrie.

Fumatul: dicontinuitatea MB i tranziia mezenchimal-epitelial (EMT): dezagregare, modificri de form, motilitate ( Sohal
et.al.)

Loss of tight
junction (claudins)

E
BM
LP
EMT

Fibroblast-like phenotype

Concluzii
Renunarea la fumat este una dintre cele
mai eficiente metode de a preveni morbimortalitatea prin BPOC
Fumtorii cu BPOC au caracteristici diferite
comparativ cu nefumtorii fr BPOC:
tenteaz mai rar oprirea fumatului i au
anse mai mici de reuit
Interveniile nefarmacologice sunt eficace la
pacieni evaluai n vederea depistrii BPOC
Terapia farmacologic nsoit de consiliere
sunt obligatorii la fumtorii cu BPOC