Eur Respir J 2010; 35: 27–33 DOI: 10.1183/09031936.00072909 Copyrig ! ER" Jour#$%s &!

' 2010

(ER"(EC)I*E

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n association between tobacco smoke and

.eri#g Dues!io#s $.is-/ (ri# ! -.hina" where of tobacco smoke in !atients at there is not only an increasin risk of infection or infected with u!take of tobacco smokin '#( [&" +].-o infect .y ! ese $! ! e .become the third commonest By contrast" the interactioncause of death lobally by the between TB and '#( infection year $020" ecli!sin deaths became evident soon after thefrom '#( and TB [3]. #n this !ers!ective throu h the tar eted marketin we further hi hli ht the strate ies of tobacco > com! Di4isio# o/ (u%.TB and '#( with the There is now consider-able evidencedevelo!ment of chronic confirmin the !resence" stren th and consistency of thisobstructive !ulmonary disease and chronic association and the different(.$i%: atory r4JsKi$/ri-$. 1).o#o%ogy0 anies" Dep! o/ 7e'i-i#e0 but J F%oor O7? also +roo!e in "./) levels at which it o!erates.er #e sGour#$%s. ion # and "ou! >/ri-$ res!ir EC.i%% /i#' E$r# C7E $--re'i!$!io# . *ore recently"4frica" 4sia" the #ndian research has focused on the role subcontinent and . :ou .-. I"" 3C1936 -1399C3003 3 O#%i#e I""3 090 '!% 3H 7 ?ER 1 27 ..uur many 2ospi!$% count O. This '#( e!idemic commenced" anddramatic !rediction is based on new associations continue to bethe fact that the e!idemic will reco nised" includin treatment-centre on the lar e !o!ulations related com!lications and dru of develo!in countries in interactions [)]..-./ will e!idemiolo ical studies [$%&].ou! pri#!e' -opy o/ ! is issue EHRO(E>3 RE"(IR>)OR: JO HR 3>& or $! o#%i .erG.$-1 o/ ! e $#s. !ulmonary disability (fi .!otential associations linkin tobacco smoke" air !ollution" tuberculosis has been debated for (TB) nearly 100 yrs [1].ser4$ ries a!ory hi h 7 9 and 2 risin 5 !reva lence C of $ cofact p ors e such as air) o !ollut . #ndoor air !ollution is a second risk factor for TB and" althou h0ecent !redictions based u!on often linked with !assive smokecurrent e1!osures to risk inhala-tion" emer es as anfactors and disease trends inde!endent risk factor insu est that .*O&H 7E 35 Re-ei4e': 7$y 05 2009 o./.ei#/o. ions" >--ep!e' $/!er re4isio#: Ju%y 19 2009 Europe$# Respir$!ory Jour#$% ! is $r!i-%e.

e searched . <inally" we discuss their !otential combined im!act and !ro!ose strate ies for addressin these collidin e!idemics.er-u%osis A)?B $#' ./ [10]. .$%2.-.&) million !atients co-infected with '#( died of TB in $003 [$1]" and TB is the leadin cause of death amon !eo!le livin with '#(" even in those receivin antiretroviral thera!y.-. =o lan ua e restrictions were im!osed" althou h only 7n lish lan ua e studies were eventually included. 4#/D remains the leadin cause of death in 4frica./ e!idemic is" in addition" bein fuelled by industrialisa-tion and the ram!ant s!read of TB and '#( [10%12]. *>3 5:& "7I) E) >&.ee# !o.e !resent each interaction se!arately" and review the !ossible biolo ical mechanisms involved.3.to middle-income countries only &0E is related to smokin and a further (os!C)? s!ru-!ur$% $ir. This !ers!ective article aims to hi hli ht these !otential interactions and their !ublic health im!lications.o1i#g0 2I*0 !u.$) million !eo!le had become infected in that year and $./ and '#(. By the end of that year" 22 million !eo!le (ran e 20%2+ million) were livin with '#(" $. !u.e#! o/ CO(D Ris1 o/ %$!e#! i#/e-!io# (rogressio# !o $-!i4e 'ise$se FI+HRE 1.$-!eriu.i%i!y.o-ys!is Giro4e-i p#eu.er-u%osis.(ER"(EC)I*E R. #t kills more than ) million !eo!le !er year" with more than 50E of those deaths occurrin in the develo!in world [$&]. .2 million new TB cases" includin 0.o#$ry 'ise$se ACO(DB .$--o s. To date only one-third of the estimated 6. )? 'is$. 4 further estimate is that" in hi h-income countries" 32E of .ro#i.orld 'ealth -r aniCation are that in $003 there were 6.5 million TB deaths [$1].urrent estimates of tobacco smokin rates are &6E for males and 5E for females in low.& !er day for all +")$5"0)1"5$2 inhabitants of the world [$]. 8nlike the smokin 99e!idemic:: in the develo!ed world" which occurred at a time when e1!osure to TB and environmental !ollution was decreasin " the modern . (C(: (#eu.-./ mortality is related to smokin " while in low.o#i$. The reference lists of these reviews were also used to su!!lement the search.3 (ran e $.e!.i! resu%!$#! pu%. The Flobal Burden of /isease and 0isk <actors !ro@ect confirmed that" in $00&" .-. The latest estimates from the . 35 3H7?ER 1 EHRO(E>3 RE"(IR>)OR: JOHR3>& 28 *O&H7E .-. The emer ence of dru -resistant TB in countries with a hi h '#( !revalence !oses an additional !ublic health threat" not only to !eo!le with '#( but also to the broader community.-.) million cases of multidru -resistant (*/0)-TB and 1.'->The 8nion mono ra!h on TB and tobacco control? @oinin efforts to control two related lobal e!idemics:: [$0]A this was used as an additional resource to com!lement our searches.o#$ry 7or!$%i!y /ro. The e1tent to which these factors interact in both additive and syner istic ways to !roduce chronic lun disease" and es!ecially chronic diseases of the airways" is only now bein realised./ [5" 6].-. 4round 0.s!ru-!i4e pu%.1 million died of 4#/D [$$]. "I5E OF )2E )?0 2I* "7O@I3+ >3D CO(D E(IDE7IC" -ne-third of the world:s !o!ulation" or $ billion !eo!le" is thou ht to be latently infected with 7y-o./ and tobacco smokin . im!ortant in the !atho enesis of . Tobacco is the sin le most !reventable cause of death in the world today.3+2 trillion ci arettes were manufac-tured" an avera e of $.$y 'ise$se 7E)2ODO&O+: >3D "E>RC2 ")R>)E+: . Bey words included TB" '#(" . #n addition" we identified three systematic reviews [$%&] on the association between tobacco and TB" one systematic review on the association between tobacco and '#( [1&] and several narrative reviews [1)%16] on the association between tobacco and all the conditions of interest. #n $00+" a!!ro1imately ). #n addition" we identified a com!rehensive re!ort entitled 994 ./ was the fourth leadin cause of death worldwide" accountin for ).3 million !eo!le needin antiretroviral thera!y under current treatment recommendations have received thera!y [$2].and middle-income countries" and 23E for males and $1E for females in hi h-income countries [$].ub*ed for !eer-reviewed literature !ublished over the last three decades with a focus on studies that re!orted data on the associations between smokin " TB" . ?ro#. (o!e#!i$% i#!er$-!io#s . 7vidence for this demo ra!hic shift towards an a ein !o!ulation and the develo!in world is already evident in the results of !revalence surveys of .1E of total deaths [3].i!is >--e%er$!e' 'e4e%op.o.

/ cases in hi h-income countries and $E in low.0B A1. This formula has been a!!lied to the estimation of the combined effect of smokin and solid fuels (biomass fuels !lus coal) in . These associations also !ass the test of biolo ical !lausibility. <rom this model" the overall im!act (combined attributable risk) of n inde!endent factors may be iven by the followin formula? # alcohol usa e.) for latent TB infection (HTB#) and 00 of 0$. The e1cess number of cases amon !o!ulation rou!s with overconcentration of risk factors enerally outwei hs the reduction amon less affected !o!ula-tion rou!s" thus the actual im!act could even be lar er. #mmunolo ical mechanisms that under!in the mechanistic link between smokin and TB are unclear" althou h several have been !ro!osed [+" $3].7B A1. #n that study" 5$E of .2 A1.0 0 2. Thus" even if the true effect is modest" the !o!ulation-attributable risk (. The real im!act of any risk factor is determined by the ma nitude of the association ( i.3 0 2. 4lthou h the effect is Guite consistent across meta-analyses" the estimated relative risk (00) is modest.or!$%i!y "!u'ies # "&>7> Q2R &I3 Q3R ?>)E" QSR 06 A1. #n the !ast few years" three inde!endent systematic reviews and meta-analyses have synthesised a lar e body of evidence on tobacco and TB [$%&].1– 3.1 05 A1. (ER"(EC)I*E 2)E to indoor smoke from biomass fuels [$)]. >""OCI>)IO3 ?E)9EE3 )O?>CCO "7O@I3+ >3D )? 4lthou h the association between tobacco smoke and TB has been debated for over a century [1]" only recently has clear e!idemiolo ical evidence emer ed.40i is the .ee# s.SB - . The e1tent to which such interventions will have an im!act on TB control remains unclear. #n the above-mentioned study" a deterministic com!artmental susce!tible% latent%infectious%recovered model was a!!lied for estimation of disease trend.8B A1.-.hina which !ro@ects that a com!lete cessation of tobacco and solid-fuel use would reduce the TB incidence by 1&% )$E by $022 [$+].6B A2. <or e1am!le" if the 00 for TB disease is conservatively assumed to be only 1.40iN iO1 where . These analyses indicate that smokers are almost twice as likely to be infected with TB and to !ro ress to active disease (00 of 01.40 will be about 12E. The situation is more com!le1 for an infectious disease like TB" because infected !atients also act as sources for sustainin infection in the !o!ulation" and risk factors like smokin and solid-fuel use may affect multi!le ste!s" from infection to disease and death.7–2.5B A1. 4 lar e body of scientific evidence in non-ci arettesmoke-associated animal and human models su ests that macro!ha es" .2 02.R.405 . #n other words" 12E of the TB cases in the world each year may be attributable to tobacco e1!osure [16].ombined .0 for TB mortality)" but data are difficult to inter!ret because of hetero eneity in the results across studies.and middle-income countries [$)]. #n models not usin TB or anisms )>?&E 1 >sso-i$!io#s .0– 2.0 02.0B 0 2. Benefits of Guittin to the individual are numerous" but in addition" the societal and lobal im!act have been hi hli hted by a recent !ublication from .1B 1.hinese households use solid fuels" such as wood" cro! residues and coal" for heatin and cookin [$+].+E for males and 2E for females in $002 and more than 30E of .8– 3.0 for TB disease). !u. 0eco nisin this" the #nternational 8nion 4 ainst Tuberculosis and Hun /isease" su!!orted by the Bloomber #nitiative to 0educe Tobacco" has !ut to ether several resources for tobacco cessation in TB !atients [$].or!$%i!y /ro.6– 2./ deaths and 3)E of lun cancer deaths were attributable to the combined effects of smokin and solid-fuel use./&= and .3 02.o1i#g $#' ! e re%$!i4e ris1 o/ %$!e#! !u. These reviews summarise evidence of the association between active smokin and three TB outcomes? TB infection (detected usin tuberculin skin testin )" active TB disease and mortality due to TB.40) is likely to be substantial because of the wides!read nature of tobacco e1!osure.ith the !otential clusterin and mutual interaction of smokin " solid-fuel use" '#( and TB in under!rivile ed !o!ulations>!o!ulation rou!s" even fi ures of such ma nitude could have been underestimated.7 2. #n reality" many risk factors tend to be clustered in vulnerable !o!ulations" and the assum!tion of inde!endence used in the above formula may not hold entirely.-. *>3 5:& "7I) E) >&. 7vidence is stron for TB disease" but less stron for TB infection and TB mortality.5– 01. $-!i4e )? 'ise$se 7e!$C$#$%ysis (oo%e' re%$!i4e ris1 A95P CIB .40 of the ith individual risk factors./5= T-cells [$5%20]" a!o!tosis of infected cells [21" 2$]" auto!ha y [22" 2&]" anti-mycobacterial !e!tides [2)" 2+]" interferon (#<=)-c" interleukin (#H)-1$ and tumour necrosis factor (T=<)-a are im!ortant in host immunity a ainst 7.er-u%osis [23].e.5– 01.3– 3. <urthermore" it is su ested that 2+E of mortality from lower res!iratory disease as a whole is related to indoor smoke e1!osureA by contrast" urban air !ollution is res!onsible for only 1E of . Table 1 !rovides an overview of the outcome-s!ecific !ooled 00 estimates from three inde!endent metaanalyses. #n that model" com!lete cessation of smokin and solid-fuel use by $022 would reduce the !ro@ected annual TB incidence in $022 by 1&%)$E if 50E directly observed treatment" short course (/-TD) covera e is sustained" $3%+$E if )0E /-TD covera e is sustained or 22%31E if $0E /-TD covera e is sustained [$+]. The association between tobacco and TB is now clear enou h to demand attention both from !ractisin clinicians as well as !olicymakers.)" with 20E of the !o!ulation e1!osed to tobacco smoke" the . Tobacco cessation must become an inte ral !art of all TB control !ro rammes.8B )? .e!. Dmokers are also twice as likely to die from TB (00 of 0$.S– 3. 7vidence of the im!act of tobacco smokin on TB infection has been confounded by its almost universal association with !overty" overcrowdin and )? i#/e-!io# )? 'ise$se 0 1 5 A1.40s of the individual factors are usually estimated in a multi!licative model that assumes mutual inde!endence of the factors.8 2.hina" where the national adult smokin !revalence was &6.er-u%osis A)?B i#/e-!io#0 progressio# !o $-!i4e 'ise$se $#' .3. *ulti!le risk factors are often involved for common diseases" and the .5– 2. . 00)" and the !revalence of the e1!osure in the !o!ulation. L1M.

EHRO(E>3 RE"(IR>)OR: JOHR3>& *O&H7E 35 3H7?ER 1 29 .

.6 in females) [11]. *>3 5:& "7I) E) >&. '#(%TB co-infected individuals have reduced survival [&&] and are at hi her risk for subseGuent o!!ortunistic infections [&)" &+]. #n smokers" '#( infection a!!ears to cause a form of accelerated em!hysema in youn '#(-!ositive individuals. 4lthou h this association continues to be widely reco nised by clinicians in develo!in countries [5+%55]" it has been !oorly studied [55" 56]./ [32].. ./5= T-cell numbers [&1]. 4n estimated )0E of all households worldwide (02 billion !eo!le) use solid fuels for cookin and heatin [36]. Dtrate ies to combat the e!idemics include? im!rovement of socioeconomic conditions and !olitical stabilityA develo!ment and access to im!roved dru s" dia nostic tools and vaccinesA im!roved access to treatment" addressin ender and o!era-tional research GuestionsA and combinin the efforts of TB control and '#( treatment !ro rammes. .to three-fold increased risk of develo!in . Deveral studies have demonstrated an increased risk (1./& count may not be sufficient to reduce the burden of disease if overcrowdin " alcohol and tobacco smokin are not adeGuately addressed./ [51]. 'owever" H7 *-#=F e! $%. The use of combination antiretroviral thera!y has dramatically reduced the incidence of o!!ortunistic infections in '#(-infected sub@ects [30%3$]. in smokers [+3]" but others did not [+0" +)" ++]. '#(-infected !eo!le are at increased risk of Ba!osi:s sarcoma and lym!homa" as well as !rimary lun cancer.$ in malesA -0 +. #ndoor biomass fuel burnin " in addition to air !ollution" has been well documented in case%control studies to be a si nificant risk factor for .2) to +.-. )? >3D 2I* The effect of the '#( e!idemic on TB has been well documented" with incident rates of TB" !articularly in 4frica" risin ra!idly as a result of '#( [$1]../ (odds ratios (-0s) ran in from 1. *oreover" !ro@ections from these studies hi hli ht the lobal risk" in !articular to females in develo!in countries" of obstructive airway disease from biomass fuel e1!osure.)%$. or anti ens" ci arette smoke selectively downre ulates the !roduction of #H-1$ and T=<-a [25].ausality between tobacco smoke and .# 2.+" 6)E ./ is well established and it remains the !rimary risk factor for . The risk of active TB doubles in the first year of '#( co-infection [&$]" and the risk of develo!in active disease in those who have HTB# is 010E !er yr [&2]. #n addition" several clinical studies have 30 *O&H7E 35 3H7?ER 1 EHRO(E>3 RE"(IR>)OR: JOHR3>& >""OCI>)IO3" ?E)9EE3 )O?>CCO "7O@E >3D 2I* '#( is drivin the TB e!idemic as !reviously mentioned. -ther health conseGuences of tobacco smokin in '#(-infected individuals include the risk of TB" !neumonia and mali nancy. Har er studies will be reGuired to com!are the ma nitude of the effect between '#(-infected and uninfected !o!ulations. #f tobacco smokin increases the im!act of TB in '#(-ne ative individuals" its effect in '#(-!ositive individuals may be si nificantly reater../ from tobacco smoke [3&]" the im!ortance of the 99total burden of inhaled !articles::" includin occu!ational" household and environmen-tal e1!osures" is increasin ly bein reco nised [3)%35].e! $%.# $. 4lthou h both tobacco smokin and '#( infection may be associated throu h their common links with !overty and hi h-risk behaviour" tobacco smokin a!!ears to be an inde!endent and im!ortant risk factor for contractin '#( [)$%))]. #t is noteworthy that in many !arts of 4frica !overty has worsened in the last decade" and the lobal economic downturn is likely to make the millennium develo!ment oals more difficult to attain.ost-tuberculous 99obstructive airways disease:: was described in the medical literature in the 16)0s and 16+0s by several authors [5$%5)].(ER"(EC)I*E R. -ther !otential mechanisms whereby smokin may attenuate host defence mechanisms include o1idative stress at the site of infection and im!airment or mechanical disru!tion of cilial function in the tracheobronchial tree [13]. #n overcrowded and !oor livin conditions" the combined effect of the two e!idemics is ma nified as evidenced by ./&= T-cells [&0] and reduces #<=-c-!roducin adenoid-s!ecific .6" 6)E . 4dded com!lications in co-infected individuals include dru -resistant TB and immune reconstitution inflammatory syndrome [&5]. . 4 nationwide survey in Douth 4frica" a hi h!revalence country for TB" has demonstrated that a history of !revious TB is a stron !redictor of chronic bronchitis (-0 &. )?0 2I*0 "7O@I3+ >3D ?IO7>"" FHE&" >" RI"@ F>C)OR" FOR CO(D . .i arette smoke also !revents !atho en-s!ecific e1!ansion and activation of . This is discussed below. -ther studies have demonstrated hi her viral loads [)+] and rate of !ro ression of '#( infection to 4#/D in smokers [)3" )5]" but this association has not been observed in all studies [)6%+$].+%6./&= and .+ times hi her) of community-acGuired bacterial !neumonia in those who smoke [+&% +5].o-ys!is Giro4e-i !neumonia (.-. *#F87I-B80B4=.+1 [5" 6" 12" 50]). . #nfections" !articularly in childhood" have been re arded as risk factors for .-. They further make reference to the documentation of em!hysema and TB by Haennec in the 1500s [52]. 4 !ossible reason for the conflictin results mi ht be the many confoundin factors" such as nutritional status" alcohol and !overty" which may have masked the association.$"000 !er 100"000 !o!ulation !revalence rates in certain Douth 4frican communities [&3]. *40T#= and '4HH7T [5&] re!orted that 99#t is increasin ly evident that a diffuse obstructive !ulmonary syndrome is often associated with tuberculosis::.reliminary data from a small study in sub-Daharan 4frica su!!orts the association of tobacco smoke and TB in '#(-infected individuals [)1]. Broad access to antiretroviral thera!y and TB control measures will hel! to control the e!idemic [)" &3" &6" )0]. [30] found that" althou h the risk for bacterial !neumonia is reduced by antiretroviral thera!y" the ma nitude of this reduction was si nificantly less in smokers.3.3% 11.ith increased life e1!ectancy achieved with antiretroviral thera!y" the risk of lun cancer from smokin is likely to increase further [+6].)? some studies showed a two.-.-. #t is not clear whether this a!!lies to (#eu. =icotine" throu h an interaction with a3 nicotinic acetylcholine rece!tors" enhances the re!lication of intracellular or anisms such as &egio#e%%$ and turns off !roduction of T=<-a by macro!ha es while leavin the secretion of #H-10 intact [26]. [+2] showed a doublin of the risk of develo!in TB in '#(-!ositive !eo!le who smoke. 7vidence from the community-based studies in hi hburden countries su ests that merely raisin a sin le individual:s . 4s well as the documented dose-de!endent risk of .

/ in '#( is unclear.-. 4 case%control study on the effect of e1!osure to different substances on the develo!ment of .ebb FB.1918.R.ublic health measures are reGuired to im!rove air Guality and reduce !assive e1!osure to tobacco smoke" reduce overcrowdin " im!rove housin and reduce reliance on biomass fuels in homes. /heda B" Kohnson *4" Iumla 4" e! $%. DeCer '" 4kkurt #" Fuler =" e! $%. *./ the focus of !ulmonol-o ists" and biomass fuel e1!osure the interest of !ublic health researchers. 4lso reGuired are access to antiretroviral thera!y" measures to reduce transmission of '#(" and the develo!ment of effective vaccines for TB and other res!iratory !atho ens" ho!efully also for '#( infection.003655.orld 'ealth -r aniCation" $00&. van Iyl Dmit is su!!orted by a /iscovery <oundation <ellowshi! and by the <o arty #nternational .-.-. Dlama B" . #t is now clear that in day-to-day clinical !ractice a more com!le1 !icture is emer in as the e!idemics of '#(" tobacco smokin and biomass fuel e1!osure" TB and . "H((OR) ")>)E7E3) 0. Tobacco and tuberculosis? a Gualitative systematic review and meta-analysis. 0isk of tuberculosis from e1!osure to tobacco smoke? a systematic review and meta-analysis. These interactions deserve ur ent attention and have ma@or im!lications for co-ordinated !ublic health !lannin and !olicy recommendations in the develo!-in world. #t would a!!ear that em!hy-sema occurs earlier" with fewer !ack-yrs of smokin " and may be associated with colonisation by (.ai *" e! $%. Re4 )u. Eur Respir J $00+A $3? )&$%)&+.&u#g Dis $003A 11? 10&6%10+1.linical Trials . >## Epi'e. '#( infection alone is increasin ly bein reco nised as a cause of !remature em!hysema [6$%6+]. Bates *=" Bhalakdina 4" ././. 7.-./ interact on a lobal scale.'7 e! $%. 4 clinical study. #nternational variation in the !revalence of . <ramework 3 !ro ramme and 7/. There should in addition be reater inte ration of TB" '#( and res!iratory services and the !rovision of smokin cessation !ro rammes. /heda is su!!orted by the Douth 4frican =ational 0esearch <oundation" the Douth 4frican *edical 0esearch . 4lthou h the combined effects of all the e!idemics may only be reco nised in develo!in countries" the develo!ed world is not immune to the risk. #m!act of '#( infection on the e!idemiolo y of tuberculosis in a !eri-urban community in Douth 4frica? the need for a e-s!ecific interventions.ommission (TBDus entA 78 <. Tobacco smoke" indoor air !ollution and tuberculosis? a systematic review and meta-analysis./ would assist with identification of novel tar ets for intervention and add si nificant scientific wei ht to the messa es of health advocates and lobby rou!s cam!ai nin for the welfare of !atients.linical 0esearch Dcholars><ellows Du!!ort .=. (H?&IC 2E>&)2 >3D (H&7O3>R: I7(&IC>)IO3" . J Respir Cri! C$re 7e' $00&A 130? 5$1. #n addition to the com!le1 !atholo ical !athways identified in '#(-ne ative smokers" e1cess cytoto1ic Tlym!hocyte activity" endothelial dysfunction and increased a!o!tosis have been su ested as !ossible !atholo ical mechanisms.T. There is little !ros!ect for im!rovement unless there is a concerted and coordinated effort by all involved !arties" such as health authorities" !ractitioners" researchers and society in eneral. The emer ence of multi. 0-T'70D [1$] and . #t is also not known if the use of anti-inflammatory or bronchodilator thera!y is of any value or if antiretroviral thera!y will halt the develo!ment" or !ro res-sion" of the disease./ (the B-H/ Dtudy)? a + 3 5 6 ./ !revalence usin the Burden of -bstructive Hun /isease methodolo y [10" 3)] and a similar study from Hatin 4merica [61] have identified !revious TB as a risk factor for ./ or re!resent one or several other forms of structural lun disease.atients in develo!in countries" es!ecially those with a hi h !revalence of infectious disease" freGuently !resent with com!le1 lun disease resultin from the varyin insults of tobacco smoke and other harmful environmental e1!osures" TB" '#( and . >. C%i# I#/e-! Dis $00+A &$? 10&0%10&3. ")>)E7E3) OF I3)ERE") =one declared.-. Bateman is su!!orted by the #nternational /evelo!ment 0esearch . Two recent reviews by .ollaboration #nitiative. -roCco-Hevi *" Farcia-4ymerich K" (illar K" e! $%. Giro4e-i.a!e Town .entre of . 7$r. *>3 5:& "7I) E) >&.hian . >r. I#! J )u.T.7T04.-. #n addition to the burden of tobacco smokin " air !ollution (indoor and environmental) and !overty" '#( is !revalent in many develo!in countries" !articularly in sub-Daharan 4frica. Hawn D/" Bekker HF" *iddelkoo! B" e! $%.ountries .*" e! $%.er.3.-.olle e Hondon% 8niversity of . The natural history of . =ew effective dru s and dia nostic tools are ur ently reGuired. B.I#!er# 7e' $003A 1+3? 22)%2&$." and from 7uro!e4#/" Brussels" Bel ium. Dmokin is not beneficial for tuberculosis. Feneva" . Iumla is in recei!t of fundin from the 7. Bnowled e of causal links and interactions between '#(" TB and . REFERE3CE" 1 $ 2 & ) .entre =ational #nstitutes of 'ealth rant 0$&T." $)%$3. >. .-.ai is su!!orted by rants from the . .orld 'ealth -r aniCationThe lobal burden of disease? $00& u!date. The im!act of current and !ro@ected e1!osures to these conditions will result in a heavy burden of lun diseases in resource-!oor countries in comin decades./. .-3). #nternational com!arisons of .ouncil" the 7.J" 7narson /4" e! $%.anada.-. CO3C&H"IO3 'istorically" TB and '#( have been the focus of infectious disease s!ecialists" smokin and . Hon -term follow-u! and thera!eutic intervention trials are needed. Hin ''" 7CCati *" *urray *. 4bsence of detailed clinical information in these surveys !revents conclusions about !atho!hysiolo y and whether such cases fall within the definitions of clinical . (&o" 7e' $003A &? e$0.er. .)" and by the 8niversity . The effect of the inhalation of ci arette smoke on the lun s.and e1tensively dru -resistant TB !ose a lobal threat" since s!illover throu h mi ration and travel is inevitable. <ramework 3 !ro ramme and the 7uro!ean and /evelo!in . 7astern 7uro!e has a hi h incidence of */0-TB and smokin .ood smoke e1!osure and risk of chronic obstructive !ulmonary disease.anadian #nstitutes of 'ealth 0esearch and 7uro!ean . 4. #n =orth 4merica" althou h TB may be infreGuently seen" '#( and tobacco smokin freGuently co-e1ist.-.io% $00+A 1+? )6%+$. 10 Buist 4D" *cBurnie *4" (ollmer ./.artnershi! (7/. (ER"(EC)I*E confirmed airflow limitation as a conseGuence of tuberculous disease [35" 5+" 55" 60]. [6+] have hi hli hted current knowled e on this association.

&$#-e! $003A 230? 3&1%3)0. EHRO(E>3 RE"(IR>)OR: JOHR3>& *O&H7E 35 3H7?ER 1 31 .!o!ulation-based !revalence study.

.hite =" =orman 0" e! $%./5(=) T cells !rimed for !roduction of ty!e 1 cytokines in the lun s of 7y-o. *ice deficient in .'->'T*>TB> $006. J I. . Biomass fuels are the !robable risk factor for chronic obstructive !ulmonary disease in rural Douth . Dhould interventions to reduce res!irable !ollutants be linked to tuberculosis control !ro rammesM ?7J $00&A 2$6? 1060% 1062. !u. 4vailable from www.almette-Fuerin. !u. Derbina =(" <lynn KH.aruso 4*" Derbina =" Blein 7" e! $%. Feneva" . 0ook F4" /heda B" Iumla 4./" Jew .70 !acka e.. $1 $$ $2 $& $) $+ $3 $5 $6 20 21 . #mmune res!onses to tuberculosis in develo!in countries? im!lications for new vaccines." Ba!lan F. FrotCke K7" Hewinsohn /*.er.'.u#o% $000A 1+&? $01+%$0$0. *olloy 4" Haochumroonvora!on .-. *annino /*" Buist 4D. ETper! Re4 >#!i I#/e-! ) er $003A )? 25)%261. 4ssociations between tobacco and tuberculosis.er-u%osis-infected mice. I#/e-! $003A 52? &1%&+.u#i!y $003A $3? )0)%)13. Hethal interaction? the collidin e!idemics of tobacco and tuberculosis.er.an L" e! $%.u#o% $00)A )? ++1%++3. '#(>4#/D estimates and the Guest for universal access.$-!eriu.unaids. ./& T cells have only transiently diminished levels of #<=-c" yet succumb to tuberculosis. J I. "eT )r$#s. ) or$T $003A +$? 556%563. #s smokin tobacco an inde!endent risk factor for '#( infection and !ro ression to 4#/DM 4 systemic review..hronic obstructive !ulmonary disease in !atients who have '#( infection./? risk factors" !revalence" and future trends.'->The 8nion mono ra!h on TB and tobacco control? @oinin efforts to control two related lobal e!idemics. I#! J )u.$-!eriu.hian .orld 'ealth -r aniCation" $005./5 = T lym!hocytes in control of 7y-o. &$#-e! $005A 23$? 1&32%1&52.J" Dlama B" 7narson /4. The *. J ETp 7e' 166&A 150? 1&66%1)06./" lun cancer" and tuberculosis in .&11.'. &$#-e! $005A 231? $0+5%$030. 8=4#/D" .-.ai *" *ohan 4" /heda B" e! $%.er-u%osis infection.es I#/e-! $00)A 3? 33+%355.er.&u#g Dis $00&A 5? 2+6%23+.redictors of chronic bronchitis in Douth 4frican adults. Hin ''" *urray *" .. (irulent 7y-o. I#! J )u.(ER"(EC)I*E 2$ 22 Beane K" 0emold 'F" Bornfeld '. C%i# C es! 7e' $003A $5? )3)%)53.$-!eriu. /avies .orld 'ealth -r aniCation" $006. 'arris K" /e 'aro D4" *aster DD" e! $%.hina? a time-based" multi!le risk factor" modellin study. 0ole of . Baris 7" 7CCati *.orld 'ealth -r aniCation..er-u%osis strains evade a!o!tosis of infected alveolar macro-!ha es.orld 'ealth -r aniCation" $003. 11 1$ 12 1& 1) 1+ 13 15 16 $0 7hrlich 0#" ." Fan uly /" e! $%. .hina. . T hel!er $ cytokines inhibit auto!ha ic control of intracellular 7y-o.entre> '#(/ata>7!i8!date>7!i8!d4rchive>$003 /e . <urber 4D" *aheswaran 0" =ewell K=" e! $%. I#! J )u.'->'T*>TB>$003. !u.0e!ort on the Flobal Tobacco 7!idemic" $005. 4!o!tosis" but not necrosis" of infected monocytes is cou!led with killin of intracellular bacillus . . )r$#s R "o)rop 7e' 2yg $00+A 100? $61%$65.er-u%osis. Hiu D" Ihou J" . . *aurya (" (i@ayan (B" Dhah 4. . . Dmokin and tuberculosis? an association overlooked.or >en>Bnowled e.u# 1666A +3? 2650%2655.u#o% 1666A 1+$? )&03%)&1+.260.ohen T" e! $%. . .$-!eriu.orld 'ealth -r aniCation$003 4#/D e!idemics u!date. Dmokin and tuberculosis? the e!idemiolo ical association and immuno!atho enesis. 3$! Re4 I. I. I#/e-! I..orld 'ealth -r aniCation" #nternational 8nion 4 ainst Tuberculosis and Hun /isease4 .orld 'ealth -r aniCationFlobal tuberculosis control? e!idemiol-o y" strate y" financin .-.re!ort $006.ock B*" /e Hay . 7arly emer ence of .rothers B..&u#g Dis $00$A +? 6&$%6)1. 7i-ro.. Feneva" .&u#g Dis $003A 11? $)5%$+$. &$#-e! $003A 230? 3+)%332. . 7ffects of smokin and solid-fuel use on . Feneva" . Flobal burden of . !u.

3$! Re4 I." e! $%.i arette smoke decreases !ulmonary dendritic cells and im!acts antiviral immune res!onsiveness." 'orsbur h . 0isk factors associated with !revalent '#(-1 infection amon !re nant women in 0wanda. Drugs $005A +5? 161%$05.. >.R. 3$!ure $000A &0)? &)5%&+$..enkower H" /ew *4" Bin sley H" e! $%. J I#/e-! Dis $00)A 161? 1)0% 1)5. 8ndia nosed tuberculosis in a community with hi h '#( !revalence? im!lications for tuberculosis control.1>. I#! J I. Franulysin" a T cell !roduct" kills bacteria by alterin membrane !ermeability. 4vanCini *4" 0icci 4" DcaramuCCa . 4 !ros!ective study of the risk of tuberculosis amon intravenous dru users with human immunodeficiency virus infection.u#o% $003A 3? 3+3%333. 4ntiretroviral dru s for tuberculosis control in the era of '#(>4#/D.ro@ect Team.halen . Donnenber .u#op$! o% ( $r. J I#/e-! Dis $003A 16+? D&63%D&66. J Respir Cri! C$re 7e' $00$A 1++? 3$&%321.H" Fourevitch *=" e! $%.ood 0. 3 E#g% J 7e' 1656A 2$0? )&)%))0." e! $%.D" /awe /7" Foncharova D#" e! $%.." Kohnson *4" e! $%.4<1) and B cell lym!homa leukemia-1(H) e1!ression and reduced a!o!tosis in alveolar macro!ha es from smokers. >.u#e De/i"y#'r 1660A 2? 3$1%3$5. Tomita B" . #mmune reconstitution inflammatory syndrome in '#(-infected !atients receivin antiretroviral thera!y? !atho enesis" clinical manifestations and mana ement. De1ual behavior" smokin " and '#(-1 infection in 'aitian women. J >-Duir I. "-ie#-e 1665A $5$? 1$1%1$). . /heda B" Ham!e <. I#! J Epi'e. *atsuna a B" Blein T. . /eficiency of #=<c !roducin cells in adenoids of children e1!osed to !assive smoke.ood 0" *iddelkoo! B" *yer H" e! $%. J I#/e-! Dis $00&A 160? 1+30%1+3+. '#(-1 in 'aitian women 165$% 1655.. 4n antimicrobial activity of cytolytic T cells mediated by ranulysin.op i%$ infection of established *'-D alveolar macro!ha es." Flynn K0" <ieldin B" e! $%. )& 2& 2) 2+ 23 25 26 . J>7> 166$A $+3? $0+$%$0++. The case for inte ratin tuberculosis and '#( treatment services in Douth 4frica. Borovikova H(" #vanova D" Ihan *" e! $%. I# 4i!ro thera!eutic effect of e!i allocatechin allate on nicotine-induced im!airment of resistance to &egio#e%%$ p#eu.0" 'om /" e! $%. /hasmana /K" /heda B" 0avn . The .. . 8nveilin the roles of auto!ha y in innate and ada!tive immunity. 'alsey =4" . J Respir Cri! C$re 7e' 166)A 1)1? 1$6%12). Behavioral" health and !sychosocial factors and risk for '#( infection amon se1ually 32 *O&H7E 35 3H7?ER 1 EHRO(E>3 RE"(IR>)OR: JOHR3>& Hevine B" /eretic (. . J Respir Ce%% 7o% ?io% $00&A 20? $0$%$11..#.&u#g Dis $005A 1$? +6)%+63. Boulos 0" 'alsey =4" 'olt 7" e! $%. Dmokin " '#( and non-fatal tuberculosis in an urban 4frican !o!ulation. J Respir Cri! C$re 7e' $003A 13)? 53%62.3. *>3 5:& "7I) E) >&.aramori F" Him D" e! $%. 0obbins . 7rnst .illiams BF" /ye . 4 !ros!ective study of tuberculosis and '#( disease !ro ression.er. Dten er D" 'anson /4" Teitelbaum 0" e! $%. J I. Re!ro4iro% 1665A 16? 2+1%2++.4" Thoma-8sCynski D" Teitelbaum 0" e! $%." <riedman '" e! $%.ite Doleil>K'8 4#/D .u#o% $000A 1+)? 310$%3105.4" 'artel /" Hewis (4" e! $%. =ational 8niversity of 0wanda-Kohns 'o!kins 8niversity 4#/D 0esearch Team. >.oberly KD" 'olt 7" e! $%. J I#/e-! Dis $00$A 15)? $$6%$2+. 4ccelerated course of human immunodeficiency virus infection after tuberculosis.u#e De/i"y#'r 2u. #ncreased !$1(.$-o% $00+A 16? +06%+1+.io% 166&A $2? 231%250. I#! J )u. Delwyn . . 'ow soon after infection with '#( does the risk of tuberculosis start to increaseM 4 retros!ective cohort study in Douth 4frican old miners. >. )) &0 &1 &$ &2 && &) &+ &3 &5 &6 )0 )1 )$ )2 . (a us nerve stimulation attenuates the systemic inflammatory res!onse to endoto1in.hao 4" Bulterys *" *usan anire <" e! $%. "-ie#-e $002A 201? 1)2)%1)23. . 0amin B" Bam /" <eleke B" e! $%. -utcome of '#(-associated tuberculosis in the era of hi hly active antiretroviral thera!y. *unsiff DD" 4l!ert . J >-Duir I.

" Dchoenbaum 77" Fourevitch *=" e! $%. J 3euro4iro% $003A 12? )+1%)+5.etersen F. J (u.urran 4" <alco (" .i arette smokin " bacterial !neumonia" and other clinical outcomes in '#(-1 infection. . 2I* 7e' $00+A 3? $+1%$+3. The effect of ci arette smokin on the develo!ment of 4#/D in '#(-1-sero!ositive individuals.rothers B" Friffith T4" *cFinnis B4" e! $%. Bacterial !neumonia" '#( thera!y" and disease !ro ression amon '#(-infected women in the '#( e!idemiolo ic research ('70) study.%i.res!o *" e! $%. "-$#' J "o." e! $%.raib BK" Dchechter *T" *ontaner KD" e! $%. J (u. .ark H." . <eldman KF" *inkoff '" Dchneider *<" e! $%. I#/e-!io# $005A 2+? $21%$2+.3. *>3 5:& "7I) E) >&. #ncidence and risk factors of bacterial !neumonia reGuirin hos!italiCation in '#(-infected !atients started on a !rotease inhibitor-containin re imen. The effect of ci arette smokin on lym!hocyte subsets and !ro ression to 4#/D in a cohort of homose1ual men.e em me 5 8 5 9 6 0 6 1 6 2 6 S 6 5 6 6 6 7 6 8 6 9 7 0 7 .. '#( infection is associated with an increased risk for lun cancer" inde!endent of smokin . >ID" 166+A 10? 11$1%11$+. 1 acGuired !neumonia in '#(-infected in!atients in the hi hly active antiretroviral thera!y era.r '# 96 5 7 12 .orGueddu 7" .u#e De/i. Re!ro4iro% 166+A 12? 23&%252. I#! J I#/e-! Dis $00)A 6? $05%$13. . 9S 95 !u I#! active homose1ual men? the *ulticenter 4#/D . *i ueC-Burbano *K" 4shkin /" 0odri ueC 4" e! $%.linical 0esearch on 4#/D. 4 !ros!ective study of '#( disease !ro ression in female and male dru users.i arette smokin and drinkin of alcohol are not associated with ra!id !ro ression to acGuired immunodeficiency syndrome amon homose1ual men in =orway.onley HK" Bush TK" Buchbinder D.ebber *. Burns /=" 'illman /" =eaton K/" e! $%. >ID" 1662A 3? 30)%310. >.o-ys!is -$ri#ii and community-acGuired !neumonia with tobacco use in '#( disease. 7 2 .%i. 6 3 *i ueC-Burbano *K" Burbano L" 4shkin /" e! $%. ." e! $%. J >-Duir I. Birk F/" *erlo . C%i# I#/e-! Dis $003A &)? 102%110.ro rams for . J Respir Cri! C$re 7e' $003A 13+? )2$%))). 4ssociation of ci arette smokin with '#( !ro nosis amon women in the '440T era? a re!ort from the women:s intera ency '#( study. . Falai =" .u#e De/i."y#'r 2u. 4ssociations of ci arette smokin with viral immune and co nitive function in human immunodeficiency virus-sero!ositive women." e! $%. The association between ci arette smokin and selected '#(-related medical conditions.. He *oin (" 0abaud . 5 6 .oker 0K" e! $%. >. 2I* 7e' $005A 6? +06%+1).7e' 166&A $$? $06%$1$.2e$%! 1661A 51? 16&%16+. 7skild 4" .ohort Dtudy. C%i# I#/e-! Dis $00+A &2? 60%65. . >ID" 1666A 12? $)3%$+$.esch K" e! $%. J >-Duir I. =ieman 0B" <lemin K" . *adeddu F" . Bacterial community /ia sus $5 . #ncreased risk of (#eu.ommunity . J +e# I#!er# 7e' $00)A $0? 11&$%11&). Bacterial !neumonia in '#(infected !atients? use of the !neumonia severity inde1 and im!act of current mana ement on incidence" aetiolo y and outcome."y#'r 2u." Kournot (" e! $%.ambosu <" e! $%. Terry Beirn . >. >''i-! ?io% $002A 5? 26%&2." -:/riscoll .o@na (" 0obles H" Dkolasky 0H" e! $%. #m!act of tobacco use on the develo!ment of o!!ortunistic res!iratory infections in '#( sero!ositive !atients on antiretroviral thera!y. Flobal strate y for the dia nosis" mana ement" and !revention of chronic obstructive !ulmonary disease? F-H/ e1ecutive summary.R. The im!act of ci arette smokin on mortality" Guality of life" and comorbid illness amon '#(-!ositive veterans.2e$%! $00+A 6+? 10+0%10+). 7 3 0abe B<" 'urd D" 4nCueto 4" e! $%. 7ffect of smokin on the clinical !ro ression of '#(-1 infection. C%i# I#4es! 7e' 166$A 1)? 201%205. Bohli 0" Ho J" 'omel . Re!ro4iro% 1663A 1&? &)1%&)5.

EHRO(E>3 RE"(IR>)OR: JOHR3>& *O&H7E 35 3H7?ER 1 33 .

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