THE BENEFITS OF SMOKING CESSATION ON PATIENTS WITH COPD – A NARRATIVE REVIEW

103
TB S C PHE ENEFITS OF MOKING ESSATION ON ATIENTS
WITH ARRATIVE EVIEWCOPD – A N R
An onio-And ei Co ea , And eea Ti no eanu , And eea-Nicole a Malaescu ,
1,5 4,5* 1,2,5
And eea-Roxana Flo escu , Ma ius E emia , Flo in-Dumi u Mih an ,
1,3,5 5 1,2,5
ăl
Ancu a-Alina Cons an in 1,2
Co esponding Au ho : And eea Ti no eanu4,5*
1. Na ional Ins i u e o Pneumoph hisiology "Ma ius Nas a", Bucha es ;
2. "Ca ol Da ila" Uni e si y o Medicine and Pha macy, Bucha es ;
3. “Vic o Babeș” Uni e si y o Medicine and Pha macy, Timișoa a;
4. G igo e T. Popa Uni e si y o Medicine and Pha macy, Iași, Romania;
5. Ae Pu Romania, Bucha es , Romania.
Abs ac
Ch onic obs uc i e pulmona y disease (COPD) is a majo heal hca e p oblem and an impo an
cause o mo ali y wo ldwide, causing 3,23 million dea hs in 2019, 90% o COPD dea hs in hose
unde he age o 70 in low and middle-income coun ies acco ding o WHO (Wo ld Heal h
O ganiza ion). COPD is he hi d leading cause o dea h globally, wi h 24% o pa ien s dying
wi hin fi e yea s o diagnosis . Smoking is he mos common isk ac o o COPD, as obacco
[1]
smoke con ains a la ge numbe o oxic subs ances ha a e bo h he cause o COPD and he
main ac o implica ed in he p og ession o he disease .
[2]
This na a i e e iew aims o p o ide scien ific help o heal hca e p o essionals o unde s and
he impo ance o ocusing on smoking cessa ion amongs pa ien s wi h COPD as he main
ea men me hod, besides pha macological he apy. The global bu den o COPD mo ali y
mus be add essed h ough effo s o educe exposu e o isk ac o s, assess indi idual pa ien
isk, and use ea men s ha lowe mo ali y. In coun ies ha ha e adop ed comp ehensi e
s a egies o p e en ion and ea men , COPD- ela ed mo ali y a es ha e declined. The
la es esea ch poin s ou he impo ance o smoking cessa ion in he p ognosis and quali y o
li e among COPD pa ien s.
Keywo ds: Tobacco smoking, ch onic obs uc i e pulmona y disease, COPD, smoking
cessa ion.
Rezuma
Boala pulmona ă obs uc i ă c onică (BPOC) es e o p oblemă majo ă de asis enă medicală și o
cauză impo an ă de mo ali a e la ni el mondial, p o ocând 3,23 milioane de decese în 2019,
90% din decesele BPOC la cei sub 70 de ani în ă ile cu eni u i mici și medii, con o m OMS
(O ganizaia Mondială a Sănă ăii). BPOC es e a eia cauză de deces la ni el global, 24% din e
Gene al Re iews In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
/inmed-20 4-031210.2478 2
104
In oduc ion
COPD is a ch onic, incu able, and li e-
h ea ening espi a o y disease caused by
a ious ac o s. I is a majo cause o
mo bidi y and mo ali y in economically
de eloped na ions and is inc easingly
eme ging as a significan heal h conce n in
de eloping coun ies . COPD is
[3]
cha ac e ized by ch onic ai flow limi a ion,
ha is no en i ely e e sible, gene ally
p og essi e, and associa ed wi h an
inflamma o y pulmona y esponse o oxic
pa icles and gases .
[4]
COPD is a widesp ead disease, affec ing 10%
o he global popula ion, and acco ding o he
e alua ions pe o med by WHO, COPD will
become he hi d leading cause o dea h by
2030 .
[5]
The e a e many isk ac o s o de eloping
COPD, and cu en esea ch show ha
smoking, bio uels, indoo , ou doo ai
pollu ion and indus ial dus a e he majo
en i onmen al isk ac o s. Howe e , he
mos impo an cause o COPD emains
ciga e e smoking .
[3]
The 2023 WHO epo on he global obacco
epidemic showed ha obacco consump ion
killed an as ounding 8.7 million people e e y
yea . And e en mo e shocking is ha 1.3
million o hese dea hs a e among people
who do no use obacco, including in an s and
child en. In pa icula , women and child en
pacieni decedând în decu s de cinci ani de la diagnos ica e. Fuma ul es e cel mai ec en
ac o de isc pen u BPOC, deoa ece umul de u un conine un numă ma e de subs ane
oxice ca e sun a â cauza BPOC, câ și p incipalul ac o implica în p og esia bolii.
Aceas ă e izui e na a i ă își p opune să o e e aju o ș iinific p o esioniș ilo din domeniul
sănă ăii pen u a înelege impo ana concen ă ii asup a enună ii la uma în ândul
pacienilo cu BPOC ca me odă p incipală de a amen , pe lângă e apia a macologică.
Po a a globală a mo ali ăii BPOC ebuie abo da ă p in e o u i de educe e a expune ii la
ac o ii de isc, e alua ea iscului indi idual al pacien ului și u iliza ea a amen elo ca e scad
mo ali a ea. În ă ile ca e au adop a s a egii cup inză oa e de p e eni e și a amen , a ele
mo ali ăii lega e de BPOC au scăzu . Cele mai ecen e ce ce ă i subliniază impo ana
enună ii la uma în p ognos icul și cali a ea ieii în ândul pacienilo cu BPOC.
Cu in e cheie: uma ul de u un, boală pulmona ă obs uc i ă c onică, BPOC, enuna ea la
uma .
Gene al Re iews
105
a e ulne able o second-hand smoke
exposu e .
[6]
Al hough passi e smoking is also ela ed o
de eloping COPD , ac i e smoking has been
[3]
associa ed wi h COPD se e i y, pa ien 's
quali y o li e and como bidi ies . Ciga e e
[4]
smoke s ha e a highe p e alence o
espi a o y symp oms, abno mal lung
unc ion, a g ea e annual decline in FEV1
( o ced expi a o y olume in 1 s) and a g ea
mo ali y a e compa ed wi h non-smoke s .
[7]
In spi e o he ac ha a e o ciga e e
smoking is dec easing in se e al coun ies, i
emains a se ious h ea o public heal h
wo ldwide, pa icula ly in Sou h-Eas Asia as
well as in Eas e n Eu ope wi h he wo ld`s
la ges numbe o smoke s. The WHO
es ima es ha by 2050 he e will be 1,5
billion smoke s globally .
[8]
E en hough smoking is he p ima y cause o
COPD, i does no lead o COPD in all smoke s,
as in he s udy conduc ed by Fle che e al.,
ai way obs uc ion was obse ed in 12% o
he mode a e smoke s and 26% o he hea y
smoke s .
[9]
Also, in an umb ella e iew conduc ed by
Hol je and all. s a ed ha ac i e smoking, as
compa ed o nonsmoke s, is he main isk
ac o o COPD .
[10]
COPD sel -managemen is an essen ial
componen o COPD managemen beha io s
such as qui ing smoking, medica ion
adhe ence, co ec inhale use, heal hy die
and physical ac i i y .
[11]
The impo ance o smoking cessa ion canno
be unde s a ed, as many s udies showed he
benefi s almos all smoke s ha e ega dless
he age o qui ing o he cumula i e amoun
o obacco exposu e. Whe eas he educ ion
isk is apid o o he s diseases such as
ca dio ascula disease, o cance and COPD
he educ ion isk is mo e g adual, indica ing
he impo ance o smoking cessa ion a a
young age in li e o main ain espi a o y
heal h .
[12]
Physiopa hology
COPD is a disease ha is cha ac e ized by
p og essi e ai flow limi a ion ha is no ully
e e sible and i is associa ed wi h an unusual
inflamma o y esponse o he lungs o
noxious pa icles and gases .
[13]
COPD is a complex obs uc i e illness ha
includes ch onic obs uc i e b onchioli is
wi h fib osis and obs uc ion o small ai ways,
emphysema wi h expansion o ai spaces and
des uc ion o lung pa enchyma, loss o lung
elas ici y and closu e o small ai ways , bu
[13]
also an inc eased mucus sec e ion, plasma
leakage and expansion o submucous
glands .
[9]
The p ima y p o ec i e ba ie agains
inhaled oxic subs ances and mic obes is
conside ed o be he b onchial epi helium, as
i is playing a i al ole in main aining issue
homeos asis. Any dis up ion in homeos asis
accen ua es he inflamma o y esponse and
epai p ocess .
[14]
I i an s in he ai ways ac i a e a ious cells
ha p oduce and elease chemo ac ic ac o s
ha a ac addi ional inflamma o y cells .
[9]
Inhala ion o obacco smoke is a powe ul
induce o inflamma ion bo h in espi a o y
ac bu also sys emically. Tobacco smoke
induces mucosal inflamma ion, heigh ens
oxida i e s ess and fib inogen concen a ion,
inc eases hs-CRP (high-sensi i i y C- eac i e
p o ein) and exp ession o inflamma o y
cy okines . As a esul o accumula ion o
[15]
inflamma o y mucous exuda es in he lumen
and an inc ease in he hickness o he
b onchial wall, he inflamma o y p ocess
pe sis s in hose who con inue o smoke,
despi e smoking cessa ion and p og essi ely
wo sens o e ime . Se e al inflamma o y
[16]
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews
106
cells ypes a e in ol ed in he
physiopa hology o COPD, including
mac ophages, neu ophils and T-cells , along
[13]
wi h adap i e inflamma o y immune cells like
CD4, CD8, and B lymphocy es and some imes
eosinophils .
[16]
Neu ophils a e he inflamma o y cells ha
play a cen al ole in he pa hogenesis o
COPD, spu um and blood neu ophilia is an
impo an hallma k o COPD and a ma ke o
COPD se e i y .
[17]
Ciga e e smoke educes he de o mabili y o
neu ophil g anulocy es which may explain
he slow wash ou a e o hese inflamma o y
cells om he lungs in smoke s . Thei
[9]
accumula ion in COPD lungs a e significan ly
inc eased which is co ela ed wi h disease
se e i y and hei sec e ed p oduc s ha e
been shown o all majo pa hological aspec s
o he condi ion . Neu ophils elease a
[18]
se ine p o eases including neu ophil
elas ases (NE), ma ix me allop o einase
(MMP), myelope oxidase (MPO), all o which
ha e as final esul al eola des uc ion .
[17]
Neu ophils om COPD pa ien s ha e been
shown o sec e e inc eased amoun s o ROS
( eac i e oxygen species) bo h spon aneously
and ollowing s imula ion .
[18]
Al eola mac ophages a e also key playe s in
ai way inflamma ion in COPD. These cells
elease a la ge a ie y o chemokines and
cy okines such as umo nec osis ac o -alpha
(TNF-al a). Al eola mac ophages also
p oduce ROS, MMPs and ca hepsins, which
con ibu e o al eola damage and induce
fib osis media o s such as TGF-be a1
( ans o ming g ow h ac o -be a-1) o igge
ai way emodeling . Mac ophage can be
[19]
di ec ly ac i a ed by ciga e e smoke and
play a key pa in sus aining he ch onic
inflamma ion in he pulmona y issue o
COPD pa ien s . Al eola mac ophages
[16]
ob ain by b onchoal eola la age (BAL) om
smoke s a e p imed o elease highe
amoun s o ROS compa ed wi h hose
ob ained om non-smoke s .
[13]
In COPD, he adap i e immune sys em is
ac i a ed, leading o infil a ion o T-cells, B-
cells, T-helpe ype 17 (Th17) cells, along wi h
a educ ion in egula o y T cells wi hin he
ai ways. T-lymphocy es numbe s a e
inc eased in he lung pa enchyma and
ai ways o smoke s compa ed wi h ne e
smoke s, ega dless o COPD de elopmen .
CD8 a e ano he cells ha inc ease mo e
significan ly han CD4 cells, and his inc ease
in pe iphe al ai ways is linked o smoking-
ela ed ai way obs uc ion. The numbe o B-
cells in he lymphoid ollicles is also g ea ly
inc eased in ad anced s ages o COPD .
[17]
Ano he inflamma o y cells ha a e
co ela ed wi h COPD inflamma ion a e
eosinophils, bu he ole o eosinophils is less
ce ain in COPD han in as hma. Inc eased
numbe s o eosinophils ha e been epo ed in
b onchial biopsies, bu also in BAL fluid du ing
Gene al Re iews
107
acu e exace ba ion o ch onic b onchi is .
[20]
Va ious inflamma o y media o s a e
implica ed in COPD, including lipids, ee
adicals, cy okines, chemokines and g ow h
ac o s .
[20]
Oxida i e s ess (OS) also plays an impo an
ole in COPD gi ing he inc eased oxidan
bu den in smoke s . OS has impo an effec s
[13]
on bo h lung unc ion and COPD pa hogenesis.
The mos impo an effec s on pa hogenesis
caused by OS a e apop osis, emodeling o he
ex acellula ma ix, al eola epi helial inju y,
mi ochond ial espi a ion, memb ane lipid
pe oxida ion (LPO), mucus hype sec e ion, and
oxida i e inac i a ion o su ac an s and
an ip o eases .
[21]
In COPD pa ien s, ele a ed le el o OS esul s
om en i onmen al exposu e including ai
pollu an s and ciga e e smoke, and om he
ele a ed le els o eac i e ni ogen species
(RNS) and ROS eleased by mac ophages and
leukocy es du ing inflamma ion .
[21]
ROS play a c i ical ole in issue damaging
and cell inju y linked wi h nume ous
inflamma o y pulmona y diseases including
COPD . Ciga e e smoking con ains o e
[21]
1016–1017 oxidan s pe puff and a ound
4700 chemicals such as ni ogen oxides,
supe oxide adicals and pe oxyni i e .
[21]
OS a ises om an imbalance be ween
eac i e oxygen species p oduc ion and
an ioxidan de ense. Adequa e balance is
essen ial o p e en cellula damage .
[22]
Inc eased OS in COPD is linked o impai ed
an ioxidan de enses .
[23]
Impac o smoking cessa ion on
espi a o y symp oms amongs COPD
pa ien s
As people age, hei lung unc ion ypically
declines, and hei abili y o epai lung issue
and manage baseline inflamma ion is
educed. The bu den o COPD eaches i s
peak in olde adul s, as usually hey a e
pa ien s ha ha e an impo an a ie y o
como bid condi ions. Combined wi h he
na u al inc ease in como bidi ies associa ed
wi h aging, his esul s in a highe mo ali y
a e o elde ly indi iduals wi h COPD .
[24]
Many s udies ha e examined he impac o
smoking on espi a o y heal h. The
g oundb eaking esea ch by Fle che and
Pe o, published in 1977, laid he ounda ion
o ou cu en unde s anding o how smoking
damages lung unc ion and highligh ed he
c i ical impo ance o qui ing smoking .
[25]
The only in e en ion p o en o slow he a e
o lung unc ion decline in COPD pa ien s is
smoking cessa ion and is p o ed ha also
smoking cessa ion educes mo ali y. F om a
public heal h s andpoin , smoking cessa ion
is he mos effec i e ea men o COPD and
leads o a educ ion in symp oms .
[26]
The Lung Heal h S udy showed ha smoking
cessa ion in e en ions led o a educ ion in
symp oms such as dyspnea, cough, spu um
p oduc ion, and wheezing. In he s udy
conduc ed by Da id H. Au and all. I is shown
ha indi iduals who qui smoking ea lie in
he cou se o hei disease may ha e milde
symp oms and a e he e o e mo e likely o
expe ience g a e benefi s om smoking
cessa ion .
[26]
Alongside he well-es ablished pheno ypes o
b onchi is and emphysema, clinicians also
iden i y he pheno ype o COPD wi h equen
exace ba ions . Exace ba ions in COPD, a e
[25]
known o accele a e he decline in lung
unc ion, leading o educed physical ac i i y,
diminished quali y o li e, and an inc eased
isk o dea h .
[27]
The e a e many ac o s ha lead o COPD
exace ba ion, bu an impo an ole is obacco
smoking. COPD pa ien s who con inue o
smoke ha e a high a e o exace ba ions ha
necessi a e hospi aliza ion. On he o he
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews

108
hand, qui ing smoking is linked o a lowe isk
o exace ba ions, wi h he magni ude o isk
educ ion co ela ing wi h he leng h o ime
since qui ing .
[26]
COPD exace ba ions a e cha ac e ized by
wo sening o espi a o y symp oms, such as
coughing, sho ness o b ea h, inc eased
spu um p oduc ion and can be igge ed by
i al o bac e ial in ec ion. I is essen ial o
ecognize ha COPD exace ba ions a e
closely linked o he mic obio a in he
espi a o y ac , mic obio a which is
dis up ed by smoking .
[28]
The e a e some s udies ha disco e ed ha
pa ien s wi h se e e COPD ha e a highe
abundance o species om he Lac obacillus
genus compa ed o hose wi h milde o no
COPD. O he esea ch has epo ed inc eased
le els o Veillonella, S ep ococcus, and
G anulica ella, wi h he la e especially
ele a ed in la e-s age cance . This dysbiosis,
o he abno mal imbalance o bac e ial
species, is belie ed o aise le els o ROS
associa ed wi h DNA damage in he lungs .
[29]
The e ha e been some significan s udies in
he la es yea s ha highligh ed he
impo ance o cessa ion smoking among
COPD pa ien s. God esen e al. conduc ed a
p ospec i e coho s udy in ol ing 19,709
indi iduals om gene al popula ion o assess
he isk o hospi aliza ion o COPD ollowing
whe he comple e smoking cessa ion o a
educ ion in Tabaco smoking o e a 14.4 yea
pe iod. The isk o hospi aliza ion was lowe in
pa ien s wi h comple e cessa ion compa ed
o con inued smoking (RR = 0.57; 95% CI:
0.33–0.99. On he o he side, me ely educing
smoking did no show a significan educ ion
in hospi aliza ion isk compa ed o pe sis en
smoking (RR = 0.93; 95% CI: 0.73–1.18) .
[30]
Kanne a al. s udied 5,887 pa icipan s om
he Lung Heal h S udy 1, ocusing on cu en
smoke s aged 35 o 60 yea s wi h mild o
mode a e COPD. Two g oups we e gi en
ei he inhaled ip a opium b omide o a
placebo, along wi h suppo i e in e en ions,
while he hi d g oup ecei ed only smoking
cessa ion ad ice. A e fi e yea s, he
p e alence o espi a o y symp oms was
significan ly educed in he in e en ion
g oups compa ed o he con ol g oup (p <
0.0001). Those who con inued smoking had a
highe p e alence o symp oms compa ed o
hose who qui (p < 0.0001), wi h symp om
imp o emen appa en wi hin he fi s yea o
smoking cessa ion .
[30]
Ano he significan s udy was conduc ed by
Tonnesen e al., in ol ing a mul icen e ial
wi h 370 COPD pa ien s o a ying disease
se e i y, aimed a suppo ing smoking
cessa ion. The s udy assessed pa ien s using
he Sain Geo ge's Respi a o y Ques ionnai e
a baseline, six mon hs, and wel e mon hs.
Pa icipan s who qui smoking o educed
hei consump ion showed imp o emen s in
a ious ques ionnai e sco es, excep o he
Gene al Re iews
109
'Ac i i y' dimension, which emained
unchanged among hose who only educed
hei smoking .
[31]
Willemese and col. highligh ha in bo h
c oss-sec ional s udies and longi udinal
s udies is sugges ed imp o emen o he
espi a o y symp oms a e smoking
cessa ion, as he mos in e mi en symp oms
(cough, phlegm and wheeze) dec ease wi hin
1–2 mon hs a e smoking cessa ion. A e
smoking cessa ion he p e alence o cough
and wheezing educes o le els compa able
o hose o nonsmoke s, bu he p e alence o
phlegm emains sligh ly ele a ed .
[32]
On he o he hand, h ee s udies, wi h
smoking cessa ion pe iods anging om 2–6
weeks o 1–12 yea s, ound no change in he
p e alence o dyspnea ollowing smoking
cessa ion .
[32]
In a s udy conduc ed by Yong Liu and col., in
which he da a a e collec ed om 4,135
adul s aged 45 and olde , yea s wi h a his o y
o smoking, showed ha pa ien s wi h COPD
ha con inued o smoke we e mo e likely o
ha e a p oduc i e cough, ha is consis en
wi h ch onic b onchi is. This condi ion is
p ima ily due o excessi e inflamma ion and
hype sec e ion o mucus seconda y o
smoking obacco p oduc s use. Ano he
impo an conclusion eme ged om his
s udy is ha he diffe ence in he equency o
dyspnea be ween cu en and o me
smoke s was less p onounced .
[33]
Does qui ing smoking imp o es lung
unc ion?
Ch onic ai flow obs uc ion, iden ified h ough
spi ome y, is he hallma k o COPD. Maximum
expi a o y flow is de e mined by esis ance in
small ai ways (cm H₂O/L/s) and he lung's
elas ic ecoil, which d i es expi a o y flow
(L/cm H₂O). The in e ac ion o hese ac o s,
called he ime cons an , dic a es how quickly
he lungs fill and emp y. In heal hy lungs, his
ime cons an is consis en ac oss b ea hing
a es. Howe e , condi ions like emphysema,
which inc ease lung compliance o ai way
esis ance, p olong lung emp ying. Spi ome y
diagnoses fixed ai flow limi a ion by
measu ing FEV1 and he FEV1/FVC (Fo ced
i al capaci y) a io a e b onchodila o use .
[34]
Qui ing smoking p esen s a c ucial oppo u-
ni y o p e en COPD, as i slows he decline in
FEV1, he eby p e en ing smoke- ela ed
espi a o y impai men . Addi ionally,
[35]
smoking cessa ion helps p e en o he
smoking- ela ed lung diseases by posi i ely
influencing key inflamma o y and emodeling
p ocesses in he lungs .
[36]
Spi ome y is essen ial o assessing ai flow
limi a ion, pa icula ly by measu ing FEV1. A
low FEV1 is p edic i e o no only an
accele a ed decline in lung unc ion bu also
highe a es o mo bidi y and mo ali y .
[37]
Since lung unc ion na u ally dec eases o e
ime, p e en ing smoking- ela ed illnesses
should begin ea ly in li e, hough many
smoking cessa ion p og ams ace high
elapse a es .
[38]
Respi a o y symp oms alone do no p edic
changes in lung unc ion, bu smoke s wi h
ai flow obs uc ion benefi om qui ing,
ega dless o pas hea y smoking, ad anced
age, poo baseline lung unc ion, o ai way
hype esponsi eness .
[38]
Abou 30% o smoke s may no exhibi ch onic
symp oms o abno mal lung unc ion;
howe e , e en hese "heal hy smoke s"
expe ience sub le changes in lung
mo phology, inflamma ion, and unc ion.
Smoking in a iably impac s he lungs, hough
he se e i y and ex en o hese changes a y
among indi iduals . A s udy by Dha iwal J e
[32]
al. explo ed he ela ionship be ween smoking
and lung unc ion, showing ha COPD
pa ien s who qui smoking expe ienced a
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews
110
significan bu empo a y imp o emen in
FEV1 a 6 weeks (184 mL), which pe sis ed
somewha a 12 weeks (81 mL) and was
pa ially main ained a e one yea .
Addi ionally, bo h COPD pa ien s who qui
smoking and hose wi h no mal spi ome y
who qui smoking showed imp o emen in
lung ca bon monoxide ans e ac o a 6
weeks .
[39]
Pezzu o e al. ound in hei s udy ha
educing ciga e e exposu e enhances
ai flow pa ame e s and exe cise pe o mance
in pa ien s. Da a om ple hysmog aphy and
hemogasanalysis indica ed a significan
imp o emen in lung unc ion o e a sho
ea men pe iod (3 mon hs). Inc eases in
i al capaci y, FEF 25-75 (Fo ced Expi a o y
Flow 25-75%), and FEV1 we e accompanied
by a dec ease in dyspnea index sco es and
educed COHb (Ca boxyhemoglobin) le els.
They also no ed ha o mid-sized and la ge
ai ways, i akes abou a yea o FEV1
educ ions o de elop .
[35]
Spi ome ic lung age, de i ed om heigh and
FEV1 using a o mula in oduced by Mo is and
Temple, was designed o simpli y spi ome y
da a and highligh he effec s o smoking o
smoke s. While some s udies ha e explo ed
whe he sha ing spi ome ic lung age
influences beha io , li le is known abou i s
esponse o in ensi e o pa ial smoking
cessa ion. A s udy by Iwaoka M. e al.
examined changes in lung unc ion in smoke s
who achie ed comple e o pa ial cessa ion.
They ound ha smoke s who ully qui
expe ienced imp o ed lung unc ion wi hin 12
weeks, whe eas pa ial cessa ion showed no
significan sho - e m benefi s .
[37]
In a sys ema ic e iew o epidemiological da a
on smoking and he annual a e o FEV1 decline
(be a), Lee PN e al. ound ha con inuing
smoke s exhibi a be a o e 10 mL/y highe
han ne e -smoke s, wi h be a inc easing
p opo ionally o daily ciga e e consump ion.
Ex-smoke s ha e be as compa able o ne e -
smoke s, while qui e s show only sligh ly
ele a ed be as. The diffe ences in be as
be ween con inuing smoke s and qui e s do
no appea o a y significan ly by age o sex
bu a e mo e p onounced in popula ions wi h
espi a o y diseases compa ed o he gene al
popula ion .
[40]
A s udy by Tashkin e al. analyzed se ial
spi ome ic da a o assess he sus ainabili y
o sho - e m lung unc ion imp o emen s
a e smoking cessa ion. Significan gains
we e obse ed wi hin 9 o 12 weeks o
abs inence, bu hese imp o emen s we e
no main ained a 24 o 52 weeks. The
easons o his decline emain unclea ,
hough subs an ial long- e m benefi s may
equi e mo e han a yea o cessa ion. This
s udy highligh s he sho - e m espi a o y
benefi s o qui ing smoking in COPD
pa ien s, offe ing mo i a ion o smoke s wi h
COPD o pu sue cessa ion .
[41]
Gene al Re iews
111
Paul D. Scanlon e al. conduc ed a fi e-yea
p ospec i e ial wi h 3,926 smoke s wi h
mild- o-mode a e ai way obs uc ion ac oss
10 No h Ame ican cen e s. Pa icipan s we e
assigned o smoking cessa ion o non-
in e en ion g oups, wi h annual lung
unc ion assessmen s. Qui e s expe ienced
a 47 mL (2%) FEV1 imp o emen in he fi s
yea , and hei annual FEV1 decline o e ou
yea s was hal ha o con inuing smoke s.
G ea e ini ial ai way esponsi eness and
lowe lung unc ion p edic ed la ge fi s -yea
imp o emen s, while younge pa icipan s
and women showed be e ou comes o e all.
Howe e , women who con inued smoking
had g ea e FEV1 decline han men .
[38]
The ECLIPSE s udy, led by Ves bo J and
colleagues, acked 2,164 COPD pa ien s
o e h ee yea s wi h de ailed assessmen s
a baseline and mul iple ollow-ups. Tes ing
included CT scans, spi ome y, 6MWT (Six-
Minu e Walk Tes ), and bioma ke sampling.
FEV1 decline showed conside able
a iabili y, a e aging 33 mL/yea —lowe
han expec ed. Key con ibu o s o as e
decline we e con inued smoking (21 ± 3.8
mL/yea ), CT-defined emphysema (13 ± 4.2
mL/yea ), and b onchodila o e e sibili y (17
± 4.2 mL/yea ) .
[42]
Smoking cessa ion is he mos effec i e
s a egy o slow he accele a ed decline in
lung unc ion and imp o e espi a o y
symp oms in smoke s wi h COPD . When
[41]
counseling smoke s o qui , hey may a gue
hey a e oo old o benefi , smoke oo much o
qui , o ha e al eady caused i e e sible lung
damage. Howe e , s udies s ongly e u e
hese claims. Hea y smoke s gain he mos
om qui ing and isk he mos by con inuing.
Olde smoke s see simila benefi s o
younge ones in slowing lung unc ion
decline. Those wi h he wo s lung unc ion
expe ience he as es de e io a ion i hey
keep smoking, making qui ing especially
c ucial o hem .
[38]
An op imal smoking cessa ion s a egy oday
should include a comp ehensi e suppo
p og am, whe he indi idual o g oup-based,
combined wi h a fi s -line pha macological
smoking cessa ion agen , such as NRT
(Nico ine Replacemen The apy), a enicline,
o bup opion SR o h ee mon hs. I elapse
occu s, e ea men should be offe ed .
[43]
The alue o CT o he diagnosis o
smoking ela ed como bidi ies
COPD is a synd ome ha includes a di e se
ange o condi ions, all cha ac e ized by
ch onic ai flow obs uc ion, wi h a ying
con ibu ions om emphysema, small-ai way
disease, and ch onic b onchi is. This ai flow
limi a ion is i e e sible and esul s om
diffe en combina ions o cen al and
pe iphe al ai way damage as well as
emphysema ous changes, which occu due
o he des uc ion o al eola s uc u es om
p olonged exposu e o ha m ul pa icles o
gases .
[44]
Among all isk ac o s, smoking is he p ima y
known con ibu o o he de elopmen o
COPD. Howe e , he deg ee o ch onic ai flow
obs uc ion ha de elops a ies significan ly
among smoke s . Since no all smoke s will
[45]
de elop COPD, p edic i e ac o s like he
ex en o low-a enua ion a eas in indi iduals
wi hou ai way obs uc ion could help iden i y
hose a isk o de eloping he disease. Fo
ins ance, a diagnosis o COPD ia HRCT (High-
Resolu ion Compu ed Tomog aphy) can be
made by de ec ing diffuse, sca e ed low-
a enua ion a eas in he lung pa enchyma .
[46]
This is c ucial because s abilizing he disease
h ough smoking cessa ion is a key aspec o
COPD managemen .
[47]
Ea ly diagnosis o COPD allows o ea lie
ea men and imp o ed p e en ion o
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews
118
du a ion and amoun o smoking inc easing
he isk o mic o ascula complica ions, while
qui ing smoking imp o es neph opa hy .
[80]
When i comes o mo ali y, a s udy by Chi e
al. e ealed a syne gis ic ela ionship be ween
smoking and diabe es, wi h he combined
effec significan ly inc easing he isk o dea h
compa ed o ei he condi ion alone .
[81]
O e weigh o obesi y a e he s onges
p edic o s o diabe es, wi h poo die ,
smoking, abs inence om alcohol, and low
le els o physical ac i i y also independen ly
associa ed wi h inc eased diabe es isk .
[34]
The isk is highe o ype 2 diabe es han ype
1, which is ela i ely a e in he s udied age
g oups . On a e age, 20% o people wi h
'[34]
T2DM and 30% o hose wi h ype 1 diabe es
melli us (T1DM) a e smoke s, wi h smoking
mo e p e alen among men and indi iduals
om lowe socioeconomic g oups .
[78]
Se e al p ospec i e s udies ha e shown ha
smoking inc eases he isk o ype 2 diabe es
in bo h men and women . Fu he mo e, he
[34]
mic o ascula complica ions a e mo e
equen among women han among men
wi h diabe es . Al hough men wi h diabe es
[80]
consis en ly ha e a highe p e alence o
smoking compa ed o women, smoking a es
among women wi h diabe es ha e been
ising, simila o ends in he gene al
popula ion . A s udy by Thomas E ns Done
[78]
e al. no ed a significan inc ease in smoking
p e alence among women in Aus ia o e a
se en-yea pe iod, pa icula ly among hose
wi h ch onic diseases, olde age, lowe
educa ion, and mig a ion backg ounds .
[82]
Ano he s udy highligh ed ha smoking was
widesp ead among young emale T1DM
pa ien s and middle-aged T1DM and T2DM
pa ien s, wa an ing a ge ed smoking
cessa ion campaigns. Smoking in hese
pa ien s was linked o poo glycemic con ol
and mic oalbuminu ia, independen o o he
ac o s .
[83]
Resea ch on pa ien s wi h ype 1 diabe es has
epo ed nega i e effec s o obacco use on
albuminu ia and enal unc ion, wi h smoking
accele a ing he p og ession o enal disease in
hose wi h ype 2 diabe es . The s udy by
[34]
Nilsson PM e al. ound ha mic oalbuminu ia
is mo e common among smoking diabe ics
han nonsmoke s and ha smoking
con ibu es o he isk ac o s associa ed wi h
mic oalbuminu ia and neph opa hy in bo h
T1DM and T2DM .
[83]
In diabe es ca e, smoking cessa ion is
essen ial o imp o ing glycemic con ol and
educing he isk o complica ions. The
inc eased isk o diabe es dec eases fi e
yea s a e qui ing smoking and no malizes
a e 20 yea s . A s udy by Wanname hee e
'[34]
al. ound ha ciga e e smoking significan ly
inc eases diabe es isk, e en a e adjus ing
o age, BMI, and o he po en ial
con ounde s. The benefi s o qui ing
smoking become appa en a e fi e yea s,
Gene al Re iews

119
wi h he isk e e ing o ha o ne e -
smoke s only a e 20 yea s. Despi e
significan weigh gain and a highe isk o
diabe es in men who qui smoking wi hin he
fi s fi e yea s, he long- e m benefi s o
smoking cessa ion ou weigh he ea ly
ad e se effec s o weigh gain .
[84]
Impac on quali y o li e
Despi e a significan decline in obacco use in
many coun ies, smoking emains he leading
heal h isk linked o ea ly-s age disease and
dea h. Se e al s udies ha e explo ed he
connec ion be ween smoking and heal h-
ela ed quali y o li e (HRQoL), showing ha
ciga e e consump ion is associa ed wi h lowe
QoL and men al well-being . The link be ween
[85]
smoking and men al heal h is no so clea .
While mos smoke s exp ess a desi e o qui ,
many con inue because hey belie e smoking
offe s men al heal h benefi s. Bo h
quan i a i e and quali a i e s udies show ha
egula smoke s use ciga e es o cope wi h
emo ional issues, dep ession, anxie y,
s abilize mood, elax, and elie e s ess . In
[86]
ac smoking may wo sen men al heal h
h ough neu oadap a ions om ch onic use,
causing nico ine wi hd awal symp oms such
as anxie y, dep ession, and i i abili y. In hese
cases, qui ing smoking could imp o e men al
heal h ins ead o wo sening i .
[87]
The fi m belie among some smoke s ha
qui ing will nega i ely impac hei quali y o
li e p esen s a majo obs acle o cessa ion.
P o iding in o ma ion abou he long- e m
imp o emen s in li e sa is ac ion and quali y o
li e a e qui ing could offe aluable insigh s
o clinicians wo king wi h smoke s conce ned
abou he consequences o qui ing. This
knowledge could also be used o mo i a e and
educa e smoke s on a la ge scale, such as
h ough media campaigns . C oss-sec ional
[88]
s udies ha e e ealed ha smoke s end o
ha e lowe HRQoL compa ed o non-smoke s.
Addi ionally, findings om se e al longi udinal
s udies sugges ha indi iduals who smoked
a baseline expe ienced wo se physical HRQoL
a ollow-up han hose who had ne e
smoked. Fu he mo e, hose who con inued
smoking om baseline o ollow-up epo ed a
decline in HRQoL a ollow-up .
[89]
Smoking cessa ion in e en ions, like ae obic
exe cise, may also imp o e QoL. Exe cise has
immedia e benefi s o psychological well-
being, such as educing c a ings and
wi hd awal symp oms. Addi ionally, egula
exe cise p o ides well-documen ed benefi s
o QoL, ega dless o smoking s a us . The
[90]
impac o obacco on smoke s' HRQoL can
a y based on ac o s like he numbe o
ciga e es smoked and nico ine dependence.
Fo example, hea y smoke s end o ha e
lowe HRQoL sco es.
Dependen smoke s epo wo se quali y o
li e han non-dependen smoke s. O he
ac o s, such as age o smoking ini ia ion, age
o qui ing, s ages o change, and qui
a emp s, also play a ole. Smoke s who s a
be o e 15 ha e lowe HRQoL, and qui ing a
an olde age is linked o lowe HRQoL sco es.
Smoke s nea qui ing epo wo se physical
heal h, while hose no in ending o qui show
wo se men al heal h. Addi ionally, smoke s
who unsuccess ully a emp ed o qui end o
ha e poo e HRQoL .
[91]
Tobacco smoking emains a leading cause o
COPD, wi h passi e smoking also con ibu ing
o espi a o y symp oms and disease
p og ession. Managemen o COPD ocuses on
clinical goals like p e en ing disease
p og ession and minimizing symp oms, as well
as imp o ing heal h- ela ed quali y o li e,
including exe cise ole ance and emo ional
well-being. Heal h s a us, unc ional s a us,
and quali y o li e a e o en used
in e changeably o desc ibe his domain, wi h
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews
120
HRQoL being c ucial o assessing he impac o
ch onic diseases like COPD . The HRQoL o
[92]
COPD pa ien s is influenced by mul iple ac o s,
including como bidi ies like ca dio ascula
disease, diabe es, and os eopo osis, as well as
isk ac o s such as smoking, low body weigh ,
and inac i i y. HRQoL measu es he impac o
disease on daily unc ioning.
Cu en COPD ea men p o ocols ocus no
only on symp om managemen bu also on
imp o ing HRQoL. Imp o ing quali y o li e
in ol es educing exace ba ions, enhancing
lung unc ion, and encou aging smoking
cessa ion, weigh con ol, and physical
ac i i y .
[93]
As such, p omo ing smoking cessa ion among
COPD pa ien s is a c i ical p io i y o
heal hca e p o essionals. Gi en he ch onic
na u e o COPD, home heal hca e clinicians
o en ha e equen in e ac ions wi h pa ien s,
p o iding nume ous oppo uni ies o educa e
hem abou qui ing smoking. I is essen ial o
clinicians o eel confiden in assessing
pa ien s' eadiness o qui , as hese discussions
a e c ucial o encou aging cessa ion and
imp o ing QoL .
[94]
Conclusions
Smoking cessa ion emains he mos effec i e
in e en ion o slow disease p og ession and
imp o e ou comes in COPD pa ien s. This
e iew highligh s i s significan benefi s ac oss
mul iple domains. By add essing he
physiopa hology o COPD, we ha e
unde sco ed how smoking cessa ion mi iga es
ai way inflamma ion, educes oxida i e s ess,
and p ese es lung unc ion. Cessa ion leads o
measu able imp o emen s in espi a o y
symp oms, educing dyspnea, cough, and
exace ba ion equency.
Addi ionally, i s posi i e impac ex ends
beyond he espi a o y sys em, lowe ing he
isk o ca dio ascula disease, diabe es, and
lung cance - common como bidi ies in COPD
pa ien s.
Ad ances in imaging, pa icula ly CT, ha e
enhanced he ea ly diagnosis o smoking-
ela ed complica ions, ein o cing he
impo ance o qui ing smoking o p e en
u he s uc u al lung damage. Mo eo e ,
imp o ed lung unc ion ollowing cessa ion
ansla es in o be e exe cise capaci y,
educed hospi aliza ions, and o e all imp o e-
men s in daily ac i i ies. Pa ien s epo
enhanced physical and men al well-being, wi h
dec eased anxie y and dep ession le els,
highligh ing he a - eaching impac o smoking
cessa ion on quali y o li e. Gi en he
o e whelming e idence, heal hca e p o ide s
mus p io i ize smoking cessa ion s a egies as
a co ne s one o COPD managemen .
Acknowledgemen
This a icle was published wi h he suppo
p o ided by he GRANT AGREEMENT NUMBER
101008139, unde he EUREST – RISE –
Gene al Re iews
121
H2020 – MSCA – RISE – 2020 p ojec ,
implemen ed in Romania by he 'Ae Pu
Romania' Associa ion.
Con lic o in e es : The e was no conflic o
in e es .
Abb e ia ions
The ollowing abb e ia ions a e used in his
manusc ip :
Bibliog aphy
[1] “Ch onic obs uc i e pulmona y disease (COPD).”
Accessed: Ma . 02, 2025. [Online]. A ailable:
h ps://www.who.in /news- oom/ ac -shee s/
de ail/ch onic-obs uc i e-pulmona y-disease-(copd)
[2] E. T. 3 min ead, “Smoking & COPD,” COPD.ne .
Accessed: Ma . 02, 2025. [Online]. A ailable: h ps://copd.
ne /basics/causes- isk- ac o s/smoking
[3] Q. Song, P. Chen, and X.-M. Liu, “The ole o ciga e e
smoke-induced pulmona y ascula endo helial cell
apop osis in COPD,” Respi . Res., ol. 22, no. 1, p. 39, Feb.
2021, doi: 10.1186/s12931-021-01630-1.
[4] J. A. Riesco, B. Alcáza , J. A. T igue os, A. Campuzano, J.
Pé ez, and J. L. Lo enzo, “Ac i e smoking and COPD
pheno ype: dis ibu ion and impac on p ognos ic ac o s,”
In . J. Ch on. Obs uc . Pulmon. Dis., ol. 12, pp.
1989–1999, 2017, doi: 10.2147/COPD.S135344.
[5] A. Fazleen and T. Wilkinson, “Ea ly COPD: cu en
e idence o diagnosis and managemen ,” The . Ad .
Respi . Dis., ol. 14, p. 1753466620942128, 2020, doi:
10.1177/1753466620942128.
[6] “WHO epo on he global obacco epidemic, 2023:
p o ec people om obacco smoke.” Accessed: Jan. 20,
2025. [Online]. A ailable: h ps://www.who.in /
publica ions/i/i em/9789240077164
[7] M. I. Saeed e al., “TOB-STOP-COP (TOBacco STOP in
COPd ial): s udy p o ocol-a andomized open-label,
supe io i y, mul icen e , wo-a m in e en ion s udy o he
effec o ‘high-in ensi y’ s. ‘low-in ensi y’ smoking
cessa ion in e en ion in ac i e smoke s wi h ch onic
obs uc i e pulmona y disease,” T ials, ol. 21, no. 1, p.
730, Aug. 2020, doi: 10.1186/s13063-020-04653-z.
[8] D. Campagna e al., “Smoking and diabe es: dange ous
liaisons and con using ela ionships,” Diabe ol. Me ab.
Synd ., ol. 11, p. 85, 2019, doi: 10.1186/s13098-019-
0482-2.
[9] K. La sson, “Aspec s on pa hophysiological
mechanisms in COPD,” J. In e n. Med., ol. 262, no. 3, pp.
311–340, Sep. 2007, doi: 10.1111/j.1365-2796.2007.
01837.x.
[10] J. C. S. Hol je e al., “Iden i ying isk ac o s o COPD
and adul -onse as hma: an umb ella e iew,” Eu . Respi .
Re . Off. J. Eu . Respi . Soc., ol. 32, no. 168, p. 230009,
Jun. 2023, doi: 10.1183/16000617.0009-2023.
[11] M. Shnaiga , S. Downie, and H. Hosseinzadeh,
“Effec i eness o Heal h Li e acy In e en ions on COPD
Sel -Managemen Ou comes in Ou pa ien Se ings: A
Sys ema ic Re iew,” COPD, ol. 18, no. 3, pp. 367–373,
Jun. 2021, doi: 10.1080/15412555.2021.1872061.
[12] N. A. Rigo i, “Smoking cessa ion in pa ien s wi h
espi a o y disease: exis ing ea men s and u u e
di ec ions,” Lance Respi . Med., ol. 1, no. 3, pp. 241–250,
May 2013, doi: 10.1016/S2213-2600(13)70063-8.
[13] V. Aus in, P. J. C ack, S. Bozino ski, A. A. Mille , and R.
Vlahos, “COPD and s oke: a e sys emic inflamma ion and
oxida i e s ess he missing links?,” Clin. Sci. Lond. Engl.
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews
122
1979, ol. 130, no. 13, pp. 1039–1050, Jul. 2016, doi:
10.1042/CS20160043.
[14] S. Dey, M. S. Eapen, C. Chia, A. V. Gaikwad, P. A. B.
Wa k, and S. S. Sohal, “Pa hogenesis, clinical ea u es o
as hma COPD o e lap, and he apeu ic modali ies,” Am. J.
Physiol. Lung Cell. Mol. Physiol., ol. 322, no. 1, pp.
L64–L83, Jan. 2022, doi: 10.1152/ajplung.00121.2021.
[15] N. L. Benowi z, J. Same , N. Soleimanpou , and B. W.
Chaffee, “Bioma ke s o imp o ed heal h ou comes a e
smoking cessa ion,” Addic . Neu osci., ol. 5, p. 100054,
Ma . 2023, doi: 10.1016/j.addicn.2022.100054.
[16] K. H. Cza necka-Ch ebelska, D. Mukhe jee, S. V.
Ma yanchik, and M. Rudzinska-Radecka, “Biological and
Gene ic Mechanisms o COPD, I s Diagnosis, T ea men ,
and Rela ionship wi h Lung Cance ,” Biomedicines, ol. 11,
no. 2, p. 448, Feb. 2023, doi: 10.3390/biomedicines
11020448.
[17] Y. Wang, J. Xu, Y. Meng, I. M. Adcock, and X. Yao, “Role
o inflamma o y cells in ai way emodeling in COPD,” In . J.
Ch on. Obs uc . Pulmon. Dis., ol. 13, pp. 3341–3348,
2018, doi: 10.2147/COPD.S176122.
[18] A. J. A. McGuinness and E. Sapey, “Oxida i e S ess in
COPD: Sou ces, Ma ke s, and Po en ial Mechanisms,” J.
Clin. Med., ol. 6, no. 2, p. 21, Feb. 2017, doi: 10.3390/jcm
6020021.
[19] M. Hikichi, K. Mizumu a, S. Ma uoka, and Y. Gon,
“Pa hogenesis o ch onic obs uc i e pulmona y disease
(COPD) induced by ciga e e smoke,” J. Tho ac. Dis., ol.
11, no. Suppl 17, pp. S2129–S2140, Oc . 2019, doi:
10.21037/j d.2019.10.43.
[20] P. J. Ba nes, S. D. Shapi o, and R. A. Pauwels, “Ch onic
obs uc i e pulmona y disease: molecula and cellula
mechanisms,” Eu . Respi . J., ol. 22, no. 4, pp. 672–688,
Oc . 2003, doi: 10.1183/09031936.03.00040703.
[21] H. G. Dailah, “The apeu ic Po en ial o Small
Molecules Ta ge ing Oxida i e S ess in he T ea men o
Ch onic Obs uc i e Pulmona y Disease (COPD): A
Comp ehensi e Re iew,” Mol. Basel Swi z., ol. 27, no. 17,
p. 5542, Aug. 2022, doi: 10.3390/molecules27175542.
[22] X. Zhao, Q. Zhang, and R. Zheng, “The in e play
be ween oxida i e s ess and au ophagy in ch onic
obs uc i e pulmona y disease,” F on . Physiol., ol. 13, p.
1004275, 2022, doi: 10.3389/ phys.2022.1004275.
[23] B. M. Fische , E. Pa lisko, and J. A. Voynow,
“Pa hogenic iad in COPD: oxida i e s ess, p o ease-
an ip o ease imbalance, and inflamma ion,” In . J. Ch on.
Obs uc . Pulmon. Dis., ol. 6, pp. 413–421, 2011, doi:
10.2147/COPD.S10770.
[24] S. Safi i e al., “Bu den o ch onic obs uc i e
pulmona y disease and i s a ibu able isk ac o s in 204
coun ies and e i o ies, 1990-2019: esul s om he
Global Bu den o Disease S udy 2019,” BMJ, ol. 378, p.
e069679, Jul. 2022, doi: 10.1136/bmj-2021-069679.
[25] S. Ko lya o , “The Role o Smoking in he Mechanisms
o De elopmen o Ch onic Obs uc i e Pulmona y Disease
and A he oscle osis,” In . J. Mol. Sci., ol. 24, no. 10, p.
8725, May 2023, doi: 10.3390/ijms24108725.
[26] D. H. Au e al., “The effec s o smoking cessa ion on
he isk o ch onic obs uc i e pulmona y disease
exace ba ions,” J. Gen. In e n. Med., ol. 24, no. 4, pp.
457–463, Ap . 2009, doi: 10.1007/s11606-009-0907-y.
[27] J. R. Hu s e al., “Suscep ibili y o exace ba ion in
ch onic obs uc i e pulmona y disease,” N. Engl. J. Med.,
ol. 363, no. 12, pp. 1128–1138, Sep. 2010, doi:
10.1056/NEJMoa0909883.
[28] A. Domenech e al., “High isk o subclinical
a he oscle osis in COPD exace ba o pheno ype,” Respi .
Med., ol. 141, pp. 165–171, Aug. 2018, doi: 10.1016/j. med.
2018.07.004.
[29] A. Fo de e al., “Mechanisms Con ibu ing o he
Como bidi y o COPD and Lung Cance ,” In . J. Mol. Sci., ol.
24, no. 3, p. 2859, Feb. 2023, doi: 10.3390/ijms24032859.
[30] M. Unde ne , J. Pe io , and G. Peiffe , “[Smoking
cessa ion in smoke s wi h ch onic obs uc i e pulmona y
disease],” Re . Mal. Respi ., ol. 31, no. 10, pp. 937–960,
Dec. 2014, doi: 10.1016/j. m .2014.07.001.
[31] P. Tønnesen, K. Mikkelsen, and L. B emann, “Nu se-
conduc ed smoking cessa ion in pa ien s wi h COPD using
nico ine sublingual able s and beha io al suppo ,” Ches ,
ol. 130, no. 2, pp. 334–342, Aug. 2006, doi:
10.1378/ches .130.2.334.
[32] B. W. M. Willemse, D. S. Pos ma, W. Timens, and N. H. T.
en Hacken, “The impac o smoking cessa ion on
espi a o y symp oms, lung unc ion, ai way
hype esponsi eness and inflamma ion,” Eu . Respi . J., ol.
23, no. 3, pp. 464–476, Ma . 2004, doi: 10.1183/09031936.
Gene al Re iews
123
04.00012704.
[33] Y. Liu e al., “Smoking du a ion, espi a o y
symp oms, and COPD in adul s aged ≥45 yea s wi h a
smoking his o y,” In . J. Ch on. Obs uc . Pulmon. Dis., ol.
10, pp. 1409–1416, 2015, doi: 10.2147/COPD.S82259.
[34] Cen e s o Disease Con ol and P e en ion (US),
Na ional Cen e o Ch onic Disease P e en ion and Heal h
P omo ion (US), and Office on Smoking and Heal h (US),
How Tobacco Smoke Causes Disease: The Biology and
Beha io al Basis o Smoking-A ibu able Disease: A
Repo o he Su geon Gene al. in Publica ions and Repo s
o he Su geon Gene al. A lan a (GA): Cen e s o Disease
Con ol and P e en ion (US), 2010. Accessed: Jan. 20,
2025. [Online]. A ailable: h p://www.ncbi.nlm.nih.
go /books/NBK53017/
[35] A. Pezzu o, C. Spo o, B. Vincenzi, and G. Tonini,
“Sho - e m effec i eness o smoking-cessa ion ea men
on espi a o y unc ion and CEA le el,” J. Comp. Eff. Res.,
ol. 2, no. 3, pp. 335–343, May 2013, doi: 10.2217/ce .
13.25.
[36] E. Maci, F. Comi o, A. M. F ezza, G. Tonini, and A.
Pezzu o, “Lung nodule and unc ional changes in smoke s
a e smoking cessa ion sho - e m ea men ,” Cance
In es ., ol. 32, no. 8, pp. 388–393, Oc . 2014, doi:
10.3109/ 07357907.2014.919308.
[37] M. Iwaoka and T. Tsuji, “Twel e Weeks o Success ul
Smoking Cessa ion The apy wi h Va enicline Reduces
Spi ome ic Lung Age,” In e n. Med. Tokyo Jpn., ol. 55, no.
17, pp. 2387–2392, 2016, doi: 10.2169/in e nalmedicine.
55.6844.
[38] P. D. Scanlon e al., “Smoking cessa ion and lung
unc ion in mild- o-mode a e ch onic obs uc i e
pulmona y disease. The Lung Heal h S udy,” Am. J. Respi .
C i . Ca e Med., ol. 161, no. 2 P 1, pp. 381–390, Feb.
2000, doi: 10.1164/aj ccm.161.2.9901044.
[39] J. Dha iwal e al., “Smoking cessa ion in COPD causes
a ansien imp o emen in spi ome y and dec eases
mic onodules on high- esolu ion CT imaging,” Ches , ol.
145, no. 5, pp. 1006–1015, May 2014, doi: 10.1378/
ches .13-2220.
[40] P. N. Lee and J. S. F y, “Sys ema ic e iew o he
e idence ela ing FEV1 decline o gi ing up smoking,” BMC
Med., ol. 8, p. 84, Dec. 2010, doi: 10.1186/1741-7015-8-
84.
[41] D. P. Tashkin, S. Renna d, J. Taylo Hays, D. Law ence,
J. P. Ma on, and T. C. Lee, “Lung unc ion and espi a o y
symp oms in a 1-yea andomized smoking cessa ion ial
o a enicline in COPD pa ien s,” Respi . Med., ol. 105, no.
11, pp. 1682–1690, No . 2011, doi: 10.1016/j. med.
2011.04.016.
[42] J. Ves bo e al., “Should we iew ch onic obs uc i e
pulmona y disease diffe en ly a e ECLIPSE? A clinical
pe spec i e om he s udy eam,” Am. J. Respi . C i . Ca e
Med., ol. 189, no. 9, pp. 1022–1030, May 2014, doi:
10.1164/ ccm.201311-2006PP.
[43] P. Tønnesen, “Smoking cessa ion and COPD,” Eu .
Respi . Re . Off. J. Eu . Respi . Soc., ol. 22, no. 127, pp.
37–43, Ma . 2013, doi: 10.1183/09059180.00007212.
[44] O. Ha ayama, T. Kobayashi, K. Fujimo o, and K. Kubo,
“U ili y o single-slice high- esolu ion CT in uppe lung field
combined wi h low-dose spi al CT o lung-cance
sc eening in he de ec ion o emphysema,” In e n. Med.
Tokyo Jpn., ol. 46, no. 18, pp. 1519–1525, 2007, doi:
10.2169/in e nalmedicine.46.6343.
[45] H. Omo i, K. Fujimo o, and T. Ka oh, “Compu ed-
omog aphy findings o emphysema: co ela ion wi h
spi ome ic alues,” Cu . Opin. Pulm. Med., ol. 14, no. 2,
pp. 110–114, Ma . 2008, doi: 10.1097/MCP. 0b013e3282
3 18 .
[46] K. Ku ashima e al., “High esolu ion CT and b onchial
e e sibili y es o diagnosing COPD,” Respi ol. Ca l on
Vic, ol. 10, no. 3, pp. 316–322, Jun. 2005, doi:
10.1111/j.1440-1843.2005.00701.x.
[47] F. A. A. Mohamed Hoesein e al., “CT-quan ified
emphysema in male hea y smoke s: associa ion wi h lung
unc ion decline,” Tho ax, ol. 66, no. 9, pp. 782–787, Sep.
2011, doi: 10.1136/ hx.2010.145995.
[48] J.-P. Cha bonnie e al., “Ai way wall hickening on CT:
Rela ion o smoking s a us and se e i y o COPD,” Respi .
Med., ol. 146, pp. 36–41, Jan. 2019, doi: 10.1016/j.
med.2018.11.014.
[49] G. R. Washko e al., “Lung olumes and emphysema
in smoke s wi h in e s i ial lung abno mali ies,” N. Engl. J.
Med., ol. 364, no. 10, pp. 897–906, Ma . 2011, doi:
10.1056/NEJMoa1007285.
[50] M. Remy-Ja din, J.-L. Edme, C. Boulenguez, J. Remy, I.
Mas o a, and A. Sobaszek, “Longi udinal ollow-up s udy o
smoke ’s lung wi h hin-sec ion CT in co ela ion wi h
pulmona y unc ion es s,” Radiology, ol. 222, no. 1, pp.
261–270, Jan. 2002, doi: 10.1148/ adiol.2221001154.
[51] J. E. McDonough e al., “Small-ai way obs uc ion and
emphysema in ch onic obs uc i e pulmona y disease,” N.
Engl. J. Med., ol. 365, no. 17, pp. 1567–1575, Oc . 2011,
doi: 10.1056/NEJMoa1106955.
[52] S. A. Chang, “Smoking and ype 2 diabe es melli us,”
Diabe es Me ab. J., ol. 36, no. 6, pp. 399–403, Dec. 2012,
doi: 10.4093/dmj.2012.36.6.399.
[53] J. A. Riesco, M. Hidalgo, D. Chipayo, J. J. Gómez, and F.
Za agozá, “P ofile o Ca dio ascula Disease Pa ien s Who
a e Diagnosed wi h COPD in a Smoking-Cessa ion Uni ,”
Ad . The ., ol. 37, no. 8, pp. 3562–3570, Aug. 2020, doi:
10.1007/s1232 5-020-01403-0.
[54] S. M. Mohiuddin, A. N. Mooss, C. B. Hun e , T. L.
G ollmes, D. A. Clou ie , and D. E. Hilleman, “In ensi e
smoking cessa ion in e en ion educes mo ali y in high-
isk smoke s wi h ca dio ascula disease,” Ches , ol. 131,
no. 2, pp. 446–452, Feb. 2007, doi: 10.1378/ches .06-
1587.
[55] P. W. F. Wilson, “Smoking, smoking cessa ion, and isk
o ca dio ascula disease,” Cu . T ea . Op ions
Ca dio asc. Med., ol. 8, no. 4, pp. 276–281, Aug. 2006,
doi: 10.1007/s11936-006-0048-0.
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews

124
[56] N. S. God edsen and E. P esco , “Benefi s o
smoking cessa ion wi h ocus on ca dio ascula and
espi a o y como bidi ies,” Clin. Respi . J., ol. 5, no. 4, pp.
187–194, Oc . 2011, doi: 10.1111/j.1752-699X.2011.
00262.x.
[57] A. A. Ahmed e al., “Risk o Hea Failu e and Dea h
A e P olonged Smoking Cessa ion: Role o Amoun and
Du a ion o P io Smoking,” Ci c. Hea Fail., ol. 8, no. 4,
pp. 694–701, Jul. 2015, doi: 10.1161/CIRCHEARTFAILURE.
114.001885.
[58] A. Bakh u and T. P. E linge , “Smoking cessa ion and
ca dio ascula disease isk ac o s: esul s om he Thi d
Na ional Heal h and Nu i ion Examina ion Su ey,” PLoS
Med., ol. 2, no. 6, p. e160, Jun. 2005, doi: 10.1371/jou nal.
pmed.0020160.
[59] C. Bullen, “Impac o obacco smoking and smoking
cessa ion on ca dio ascula isk and disease,” Expe Re .
Ca dio asc. The ., ol. 6, no. 6, pp. 883–895, Jul. 2008, doi:
10.1586/14779072.6.6.883.
[60] A. L. Pipe, M. J. Eisenbe g, A. Gup a, R. D. Reid, N. G.
Suskin, and J. A. S one, “Smoking cessa ion and he
ca dio ascula specialis : Canadian Ca dio ascula
Socie y posi ion pape ,” Can. J. Ca diol., ol. 27, no. 2, pp.
132–137, 2011, doi: 10.1016/j.cjca.2010.12.060.
[61] G. Gallucci, A. Ta a one, R. Le ose, A. V. Lalinga, and
A. M. Capobianco, “Ca dio ascula isk o smoking and
benefi s o smoking cessa ion,” J. Tho ac. Dis., ol. 12, no.
7, pp. 3866–3876, Jul. 2020, doi: 10.21037/j d.2020.02.47.
[62] D. Gi a d e al., “Long- e m smoking cessa ion and
hea a e dynamics in an aging heal hy coho : Is i
possible o ully eco e ?,” En i on. Res., ol. 143, no. P A,
pp. 39–48, No . 2015, doi: 10.1016/j.en es.2015.09.023.
[63] A. J. Dobson, H. M. Alexande , R. F. Helle , and D. M.
Lloyd, “How soon a e qui ing smoking does isk o hea
a ack decline?,” J. Clin. Epidemiol., ol. 44, no. 11, pp.
1247–1253, 1991, doi: 10.1016/0895-4356(91)90157-5.
[64] K. K. Teo e al., “Tobacco use and isk o myoca dial
in a c ion in 52 coun ies in he INTERHEART s udy: a case-
con ol s udy,” Lance Lond. Engl., ol. 368, no. 9536, pp.
647–658, 2006, doi: 10.1016/S0140-6736(06)69249-0.
[65] D. Twa della, D. Ro henbache , H. Hahmann, B.
Wüs en, and H. B enne , “The unde es ima ed impac o
smoking and smoking cessa ion on he isk o seconda y
ca dio ascula disease e en s in pa ien s wi h s able
co ona y hea disease: p ospec i e coho s udy,” J. Am.
Coll. Ca diol., ol. 47, no. 4, pp. 887–889, Feb. 2006, doi:
10.1016/j.jacc.2005.11.028.
[66] A. P. Sil a e al., “Influence o smoking cessa ion d ugs
on blood p essu e and hea a e in pa ien s wi h
ca dio ascula disease o high isk sco e: eal li e se ing,”
BMC Ca dio asc. Diso d., ol. 16, p. 2, Jan. 2016, doi:
10.1186/s12872-015-0180-4.
[67] B. P. Yawn and A. Kaplan, “Co-mo bidi ies in people
wi h COPD: a esul o mul iple diseases, o mul iple
mani es a ions o smoking and eac i e inflamma ion?,”
P im. Ca e Respi . J. J. Gen. P ac . Ai w. G oup, ol. 17, no.
4, pp. 199–205, Dec. 2008, doi: 10.3132/pc j.2008.00021.
[68] E. Ba ei o, V. Bus aman e, V. Cu ull, J. Gea, J. L. López-
Campos, and X. Muñoz, “Rela ionships be ween ch onic
obs uc i e pulmona y disease and lung cance : biological
insigh s,” J. Tho ac. Dis., ol. 8, no. 10, pp. E1122–E1135,
Oc . 2016, doi: 10.21037/j d.2016.09.54.
[69] D. Amicizia e al., “Sys ema ic Re iew o Lung Cance
Sc eening: Ad ancemen s and S a egies o
Implemen a ion,” Heal hc. Basel Swi z., ol. 11, no. 14, p.
2085, Jul. 2023, doi: 10.3390/heal hca e11142085.
[70] R. Uliński, I. Kwiecień, and J. Domagała-Kulawik, “Lung
Cance in he Cou se o COPD-Eme ging P oblems Today,”
Cance s, ol. 14, no. 15, p. 3819, Aug. 2022, doi: 10.3390/
cance s14153819.
[71] A. Ca aillès e al., “Como bidi ies o COPD,” Eu .
Respi . Re . Off. J. Eu . Respi . Soc., ol. 22, no. 130, pp.
454–475, Dec. 2013, doi: 10.1183/09059180.00008612.
[72] R. P. Young and R. J. Hopkins, “How he gene ics o
lung cance may o e lap wi h COPD,” Respi ol. Ca l on Vic,
ol. 16, no. 7, pp. 1047–1055, Oc . 2011, doi: 10.1111/j.
1440-1843.2011.02019.x.
[73] G. J. C ine e al., “Ch onic Obs uc i e Pulmona y
Disease and Lung Cance : A Re iew o Clinicians,”
Ch onic Obs . Pulm. Dis. Miami Fla, ol. 9, no. 3, pp.
454–476, Jul. 2022, doi: 10.15326/jcopd .2022.0296.
[74] K. Szalon ai e al., “Ch onic Obs uc i e Pulmona y
Disease: Epidemiology, Bioma ke s, and Pa ing he Way o
Lung Cance ,” J. Clin. Med., ol. 10, no. 13, p. 2889, Jun.
2021, doi: 10.3390/jcm10132889.
[75] T. Goldko n, S. Filos o, and S. Chung, “Lung inju y and
Gene al Re iews
125
lung cance caused by ciga e e smoke-induced oxida i e
s ess: Molecula mechanisms and he apeu ic
oppo uni ies in ol ing he ce amide-gene a ing
machine y and epide mal g ow h ac o ecep o ,”
An ioxid. Redox Signal., ol. 21, no. 15, pp. 2149–2174,
No . 2014, doi: 10.1089/a s.2013.5469.
[76] V. A. Ki i, J. So iano, G. Visick, and L. Fabb i, “Recen
ends in lung cance and i s associa ion wi h COPD: an
analysis using he UK GP Resea ch Da abase,” P im. Ca e
Respi . J. J. Gen. P ac . Ai w. G oup, ol. 19, no. 1, pp.
57–61, Ma . 2010, doi: 10.4104/pc j.2009.00048.
[77] D. J. Magliano, E. J. Boyko, and IDF Diabe es A las 10 h
edi ion scien ific commi ee, IDF DIABETES ATLAS, 10 h
ed. in IDF Diabe es A las. B ussels: In e na ional Diabe es
Fede a ion, 2021. Accessed: Jan. 20, 2025. [Online].
A ailable: h p://www.ncbi.nlm.nih.go / books
NBK581934/
[78] V. Du lach e al., “Smoking and diabe es in e play: A
comp ehensi e e iew and join s a emen ,” Diabe es
Me ab., ol. 48, no. 6, p. 101370, No . 2022, doi:
10.1016/j.diabe .2022.101370.
[79] G. J. Molla e al., “Smoking and Diabe es Con ol in
Adul s Wi h Type 1 and Type 2 Diabe es: A Na ionwide
S udy F om he 2018 Na ional P og am o P e en ion and
Con ol o Diabe es o I an,” Can. J. Diabe es, ol. 44, no. 3,
pp. 246–252, Ap . 2020, doi: 10.1016/j.jcjd.2019.07.002.
[80] I. Be lin, V. Du lach, D. Thomas, B. Ve gès, A.-L. Le
Faou, and Wo king G oup on Smoking and Diabe es,
“Tobacco smoking and diabe es. A compa a i e su ey
among diabe ologis s and smoking cessa ion specialis s,”
P im. Ca e Diabe es, ol. 18, no. 2, pp. 241–245, Ap . 2024,
doi: 10.1016/j.pcd.2024.01.009.
[81] C. P. Wen, T. Y. D. Cheng, S. P. Tsai, H. L. Hsu, H. T.
Chan, and C. C. Hsu, “Explo ing he ela ionships be ween
diabe es and smoking: wi h he de elopmen o glucose
equi alen concep o diabe es managemen ,” Diabe es
Res. Clin. P ac ., ol. 73, no. 1, pp. 70–76, Jul. 2006, doi:
10.1016/j.diab es.2005.12.005.
[82] T. E. Do ne , H. B a h, and A. Kau zky-Wille , “Sex-
specific ends in smoking p e alence o e se en yea s in
diffe en Aus ian popula ions: esul s o a ime-se ies
c oss-sec ional analysis,” BMJ Open, ol. 10, no. 9, p.
e035235, Sep. 2020, doi: 10.1136/bmjopen-2019-035235.
[83] P. M. Nilsson, S. Gudbjö nsdo i , B. Eliasson, J.
Cede holm, and S ee ing Commi ee o he Swedish
Na ional Diabe es Regis e , “Smoking is associa ed wi h
inc eased HbA1c alues and mic oalbuminu ia in pa ien s
wi h diabe es--da a om he Na ional Diabe es Regis e in
Sweden,” Diabe es Me ab., ol. 30, no. 3, pp. 261–268,
Jun. 2004, doi: 10.1016/s1262-3636(07)70117-9.
[84] S. G. Wanname hee, A. G. Shape , I. J. Pe y, and
B i ish Regional Hea S udy, “Smoking as a modifiable isk
ac o o ype 2 diabe es in middle-aged men,” Diabe es
Ca e, ol. 24, no. 9, pp. 1590–1595, Sep. 2001, doi:
10.2337/diaca e.24.9.1590.
[85] F. Moaye i, Y.-S. A. Hsueh, D. Dun , and P. Cla ke,
“Smoking Cessa ion and Quali y o Li e: Insigh s F om
Analysis o Longi udinal Aus alian Da a, an Applica ion o
Economic E alua ions,” Value Heal h J. In . Soc.
Pha macoeconomics Ou comes Res., ol. 24, no. 5, pp.
724–732, May 2021, doi: 10.1016/j.j al.2020.11.022.
[86] G. Taylo , A. McNeill, A. Gi ling, A. Fa ley, N. Lindson-
Hawley, and P. A eya d, “Change in men al heal h a e
smoking cessa ion: sys ema ic e iew and me a-analysis,”
BMJ, ol. 348, p. g1151, Feb. 2014, doi: 10.1136/bmj.
g1151.
[87] G. M. Taylo e al., “Smoking cessa ion o imp o ing
men al heal h,” Coch ane Da abase Sys . Re ., ol. 3, no.
3, p. CD013522, Ma . 2021, doi: 10.1002/14651858.
CD013522.pub2.
[88] M. E. Pipe , S. Ken o d, M. C. Fio e, and T. B. Bake ,
“Smoking cessa ion and quali y o li e: changes in li e
sa is ac ion o e 3 yea s ollowing a qui a emp ,” Ann.
Beha . Med. Publ. Soc. Beha . Med., ol. 43, no. 2, pp.
262–270, Ap . 2012, doi: 10.1007/s12160-011-9329-2.
[89] J. Tian, A. J. Venn, L. Blizza d, G. C. Pa on, T. Dwye ,
and S. L. Gall, “Smoking s a us and heal h- ela ed quali y
o li e: a longi udinal s udy in young adul s,” Qual. Li e Res.
In . J. Qual. Li e Asp. T ea . Ca e Rehabil., ol. 25, no. 3, pp.
669–685, Ma . 2016, doi: 10.1007/s11136-015-1112-6.
[90] E. L. Bloom, H. Minami, R. A. B own, D. R. S ong, D.
Riebe, and A. M. Ab an es, “Quali y o li e a e qui ing
smoking and ini ia ing ae obic exe cise,” Psychol. Heal h
Med., ol. 22, no. 9, pp. 1127–1135, Oc . 2017, doi:
10.1080/13548506.2017.1282159.
[91] M. C. Míguez e al., “Heal h- ela ed quali y o li e
among smoking elapse s,” Psico hema, ol. 30, no. 1, pp.
27–32, Feb. 2018, doi: 10.7334/psico hema2017.61.
[92] G. Papadopoulos, C. I. Va da as, M. Limpe i, A.
Lina dis, G. Geo goudis, and P. Beh akis, “Smoking
cessa ion can imp o e quali y o li e among COPD
pa ien s: alida ion o he clinical COPD ques ionnai e in o
G eek,” BMC Pulm. Med., ol. 11, p. 13, Feb. 2011, doi:
10.1186/1471-2466-11-13.
[93] V. Fazekas-Pongo e al., “Heal h- ela ed quali y o li e
o COPD pa ien s aged o e 40 yea s,” Physiol. In ., Jun.
2021, doi: 10.1556/2060.2021.00017.
[94] E. A. Flo , “Smoking Cessa ion S a egies o Pa ien s
wi h COPD,” Home Heal hc. Now, ol. 33, no. 7, pp.
375–379, 2015, doi: 10.1097/NHH.0000000000000263.
In e nal Medicine 20 4 ol. X I No. 4 - www.s mi. o2X
Gene al Re iews