Environmental epidemiology applied
to urban atmospheric pollution:
a contribution from the Experimental Air
Pollution Laboratory (LPAE)
Ep id e mio lo g ia amb ie ntal ap licad a à p o luição
atmo sfé rica urb ana: uma co ntrib uição
d o Lab o rató rio d e Po luição Atmo sfé rica
Exp e rime ntal (LPAE)
1 Laboratory of
Ex p erim en t a l Air Pollu t ion , M ed ica l Sch ool,
Un iv ersit y of Sã o Pa u lo. Av. Dou t or Arn a ld o 455, Sã o Pa u lo, SP 01246- 903, Bra z il. p a n d re@osit e.com .b r a b ra ga @h sp h .h a rv a rd .ed u ca lin @u ol.com .b r gleice@u sp .b r lu iz @lim 05.fm .u sp .b r m ira glia @z a z .com .b r gyorb oh m @u sp .b r
Pa u lo Afon so d e An d ré 1 Alfésio Lu is Ferreira Bra ga 1 Ch in An Lin 1
Gleice M a rga ret e d e Sou z a Con ceiçã o 1 Lu iz Alb ert o Am a d or Pereira 1
Sim on e Georges El Kh ou ri M ira glia 1 György M ik los Böh m 1
Abstract Syst em at ic in vest igat ion on t h e effect s of h u m an ex p osu re t o en v iron m en t al p ollu t ion u sin g scien t ific m et h od ology on ly began in t h e 20t h cen t u ry as a con sequ en ce of several en v iron -m en t a l a ccid en t s follow ed by a n u n ex p ect ed -m ort a lit y in crea se a bov e ex p ect ed -m ort a lit y a n d a s a resu lt of ob serv a t ion a l ep id em iologica l a n d t ox icologica l st u d ies con d u ct ed on a n im a ls in d ev elop ed cou n t ries. Th is a rt icle rep ort s t h e ex p erien ce of t h e Ex p erim en t a l Air Pollu t ion La b ora -t ory a -t -t h e Sch ool of M ed icin e, Un iv ersi-t y of Sã o Pa u lo, con cern in g -t h e resp ira -t ory sys-t em a n d p a t h op h ysiologica l m ech a n ism s in volved in resp on ses t o ex p osu re t o p ollu t ion u sin g t ox icologica l a n d ex p erim en t a l p roced u res, com p lem en t ed by ob serv a t ion a l ep id em iologiicologica l st u d ies con -d u ct e-d in t h e cit y of Sã o Pa u lo. It a lso -d escrib es t h ese ep i-d em iologica l st u -d ies, p oin t in g ou t t h a t air p ollu t ion is h arm fu l t o p u blic h ealt h , n ot on ly am on g su scep t ible grou p s bu t also in t h e gen era l p op u la t ion , ev en w h en t h e con cen t ra t ion of p ollu t a n t s is b elow t h e lim it s set b y en v iron m en tal legislation . Th e stu d y p rovid es valu able in form ation to su p p ort th e p olitical an d econ om -ic d ecision -m ak in g p rocesses aim ed at p reservin g th e en viron m en t an d en h an cin g qu ality of life.
Key words Coh ort St u d ies; Case-Con t rol St u d ies; Air Pollu t ion ; En v iron m en t al Pollu t ion
Resumo A in v est iga çã o sob re os efeit os d a ex p osiçã o h u m a n a à p olu içã o a m b ien t a l in iciou d e m a n ei ra si st em á t i ca , com a b ord a gem ci en t í fi ca , a p en a s n o sécu lo XX, com o con seq ü ên ci a d e u m a série d e a cid en t es a m b ien t a is p erceb id os p or u m sign ifica t iv o a u m en t o n a m ort a lid a d e e com a rea liz a çã o d e est u d os ep id em iológicos observa cion a is e t ox icológicos em a n im a is. Ta is es-t u d os es-t êm se con cen es-t rad o n os p aíses con sid erad os d esen volv id os. Eses-t e ares-t igo relaes-t a a ex p eriên cia d o La b o ra t ó ri o d e Po lu i çã o At m o sf éri ca Ex p eri m en t a l (LPAE), d a Fa cu ld a d e d e M ed i ci n a d a Un iv ersid a d e d e Sã o Pa u lo, n o est u d o d os m eca n ism os fisiop a t ológicos d o sist em a resp ira t ório em fa ce d a ex p osiçã o a os p olu en t es, u t iliz a n d o a b ord a gen s ex p erim en t a is e t ox icológica s, com -p lem en t a d a s com est u d os e-p id em iológicos ob serv a cion a is n a cid a d e d e Sã o Pa u lo. Descrev e cm o esses est u d os se in serecm n o p an oracm a cm u n d ial, con vergin d o p ara u cm con sen so d e qu e a p olu içã o d o a r é p reju d icia l à sa ú d e p ú b lica , e q u e esses efeit os sã o ob serv a d os in colu siv e em con -cen t rações d e p olu en t es abaix o d os lim it es est abelecid os p ela legislação am bien t al em v igor, for-n ecefor-n d o d a d os v a liosos p a ra su b sid ia r a t om a d a d e d ecisões p olít ica s e ecofor-n ôm ica s p a ra a m e-lh oria d o m eio am bien t e.
Introduction
Lon d on , Decem b er 1952. Mr. Sm ith with d ysp -n ea , co u gh , exp ecto ra tio -n , a -n d fever o f 38oC, ca m e to th e St. Th o m a s Ho sp ita l a n d m et a crowd with ap p roxim ately th e sam e sym p tom s in th e em ergen cy ro o m . He wa s a d m itted to th e h osp ital for treatm en t. A few d ays later th is 60-year-old m an d ied .
São Pau lo, Ju n e 1991. Sílvia, 2 years old , was b rou gh t by h er m oth er to th e Ped ia trics In sti-tu te a t th e Un iversity Ho sp ita l in Sã o Pa u lo with d ysp n ea, cou gh , an d exp ectoration . Med -icated for acu te asth m a an d sen t h om e.
Alth ou gh fiction al, th ese cases were b ased o n rea l situ a tio n s: th e first in Lo n d o n’s wo rst a ir p o llu tio n d isa ster o f a ll tim e, in 1952, d u r-in g th e wr-in ter wh en a th erm a l r-in versio n p re-ven ted th e d isp ersion of air p ollu tan ts, with an adm ixture resultin g from coal an d diesel b u rn ed with a n extrem ely h igh su lfu r co n ten t. Co m -b in ed with th e tra d itio n a l Lo n d o n fo g, th ey p ro d u ced a n a cid a ero so l ca u sin g m o st o f th e m o rta lity (Lo ga n , 1953). Th e seco n d , in Sã o Pa u lo, wa s b a se d o n t h e e xp e r ie n c e o f t h e Pe d ia t rics In st it u t e’s e m e rge n cy ro o m a t t e n -d a n ce -d u rin g a win ter p erio -d with p o llu ta n t con cen tration s sligh tly ab ove cu rren tly accep t-ed th resh old s (Farh at, 1999; Lin , 1999). In b oth situ a tio n s, ep id em io lo gica l a n a lysis wa s re-qu ired to d em on strate th e association b etween a ir p o llu ta n ts a n d th e in crea se in m o rb id ity an d m ortality.
Du r in g t h e 40 ye a r s b e t we e n t h e se t wo e p iso d e s, e p id e m io lo gic a l t e c h n iq u e s h a ve m a d e gre a t st r id e s in e va lu a t in g t h e im p a ct o f a ir p o llu t io n . Th is re vie w is in t e n d e d t o d e sc r ib e su c h t e c h n iq u e s, b a se d o n o u r e x-p erien ce.
Th e system atic an d scien tific in vestigation of air p ollu tion on ly b egan in th e 20th cen tu ry a s a resu lt o f a series o f en viro n m en ta l a cci-d en ts, with a sign ifican t ob servecci-d in crease over th e exp ected m o rta lity ra te (Firket, 1931; Lo -gan , 1953; Ciocco & Th om p son , 1961). In ad d i-t io n i-t o e p id e m io lo gica l re se a rch , i-t oxico lo gi-ca l st u d ie s o n a n im a ls we re a lso co n d u ct e d . Desp ite m u ch d iscu ssio n a b o u t th eir va lid ity a n d co n t ra d ict o r y re su lt s, we co n t e n d t h a t th e two typ es of research are u sefu l an d com -p lem en tary.
Fro m a geo p o litica l p ersp ective, m o st research h as b een con d u cted in d evelop ed cou n -tries, n ot on ly b ecau se th ey h ave th e fu n d s an d resea rch fa cilities to co n d u ct it, b u t a lso b eca u se th ey en joy a fa vo ra b le p o litieca l a n d so -cia l en viro n m en t th a t p la ces va lu e o n h u m a n b ein gs (Elson , 1987; WHO, 1996a).
Toxicological studies
Th e Exp erim en ta l Air Po llu tio n La b o ra to r y (LPAE) was estab lish ed in 1979 with toxicologi-cal stu d ies on th e effects of m otor veh icle fu els (gasolin e an d eth an ol) on lab oratory an im als, an d m ain ly on th eir resp iratory system s. Brazil h ad recen tly lau n ch ed th e world’s largest alter-n a tive fu el p ro gra m , u sialter-n g alter-n o alter-n -fo ssil p ower sou rces, so th at su ch research was h igh ly rele-van t. Exp erim en ts were p erform ed in in toxica-tion ch am b ers, an d th e m ain fin d in g was alco-h ol’s lower toxicity as com p ared to fossil fu els (Bö h m et a l., 1983; Ma ssa d et a l., 1985, 1986). No tran sp osition of these fin din gs to São Pau lo’s h u m an p op u lation was p erform ed .
At th e tim e, 90% of São Pau lo’s air p ollu tion was p roduced by m otor vehicles (CETESB, 1996) a n d a lrea d y p o sed a serio u s h ea lth p ro b lem . Th ere are n ow 5 m illion veh icles, an d sin ce n o im p rovem en ts h a ve b een m a d e in th e p u b lic tra n sp o rta tio n , th e th rea t o f p o llu tio n to th e p op u lation is on th e rise.
In addition , accordin g to an ecological stu d y by Miraglia et al. (1997), in terru p tion of eth an ol u se a s a n a ltern a tive fu el is co n cen tra tin g th e u rb an tran sp ortation en ergy m atrix exclu sively on fossil com p ou n d s, d ram atically aggravatin g th e a ir p o llu tio n scen a rio in th e city o f Sã o Pa u lo a n d ca u sin g a n in crea se of 13% in m or-tality d u e to resp iratory d iseases in th e p op u la-tion over 65 years.
Th e effects o f u rb a n a ir p o llu tio n p resen t so m e co m p lex a n d sp ecific lo ca l ch a ra cteris-tics, stem m in g n o t o n ly fro m th e sp ecific sou rces of p ollu tan ts (in d u strial an d econ om ic activities, typ e of fu el u sed , u rb an traffic, etc.) b u t also from con d ition s for th eir d isp ersion . It is im p ortan t to recogn ize th e variou s cycles of con cen tration -disp ersion : day an d n igh t, week-ly an d yearweek-ly variation s, etc. (Sch wartz, 1994b ; WHO, 1996a).
Th e m a in su b sta n ces id en tified a n d m ea -su red b y th e lo ca l en viro n m en ta l a gen cy (CETESB – Companhia de Tecnologia de Sanea-mento Ambiental) are: su lfu r d ioxid e (SO2), n i-tro gen oxid es (NOx), ca rb o n m o n oxid e a n d d ioxid e (CO a n d CO2), ozo n e (O3), lea d (Pb ), an d total su sp en ded p articu late (TSP), of wh ich in h a la b le p a rticles ≤10 µ m (PM10) a re o f th e grea test co n cern . Mea su rin g a n d reco rd in g p ollu tan t con cen tration s are extrem ely im p or-tan t com p on en ts of en viron m en t ep id em iolog-ica l resea rch , a n d d isco n tin u o u s m ea su re-m en ts d u e to equ ip re-m en t re-m alfu n ction in g is th e m o st fre q u e n t p ro b le m a ffe ct in g d a t a b a se qu ality.
Th e LPAE first in vestiga ted resp o n ses b y th e resp iratory system to p ollu tion exp osu re in in h a la tion ch a m b ers with d ilu ted ca r exh a u st fu m es. It la ter a n a lyzed th e resp ira to r y fu n c-tion s of an im als exp osed to São Pau lo’s air p ol-lu tio n a n d co m p a red th em to co n tro l gro u p s kep t in a clean -air en viron m en t. Th e resu ltin g d ata led u s to con clu d e th at p ollu tion exp osu re cou ld resu lt in several h azard ou s h ealth effects, su ch a s b ro n ch itis, em p h ysem a , a sth m a , a n d even ca n cer (Bö h m et a l., 1989; Sa ld iva et a l., 1992; Pereira et al., 1995; Reym ão et al., 1997).
A n ew lin e of research on th e effects of p ol-lu tio n o n h ea lth h a s b een d evelo p ed a t th e LPAE u sin gTrad escan tiasp. p lan ts, sin ce th eir
cellu la r kern el is a b le to m u ta te in a d o se-re-sp on sive way wh en exp osed to h igh con cen tra-tion s of p ollu tan ts (Batalh a et al., 1999). Rele-va n t to th is p o in t a re th e reviews by Sa ld iRele-va & Bö h m (1998) a n d Gra n t (1998) o n a n im a l a n d p la n t in d ica to rs o f a d verse effects a sso cia ted with air p ollu tion .
Epidemiological studies
Ep id e m io lo gica l st u d ie s h a ve p la ye d a n im -p ortan t role in u n d erstan d in g th e effects of air p o llu t a n t s in a ll t yp e s o f in d o o r a n d o u t d o o r e n viro n m e n t s. De sp it e m a jo r t e ch n ica l a n d m e t h o d o lo gica l a d va n ce s in re ce n t d e ca d e s, th ere are lim itation s in h eren t to ep id em iologi-cal stu d ies:
• th ey d ep ict p a st even ts, wh en d a m a ge h a s alread y b een d on e;
• exp o su re eva lu a tio n s a re su b ject to criti-cism , esp ecia lly th o se o f cu m u la tive d o ses (ch ron ic exp osu re);
• t h e y ge n e ra lly su ffe r fro m fin a n cia l lim i-t a i-tio n s (p ro sp eci-tive co h o ri-t si-tu d ies) a n d / o r m eth od ological p rob lem s (follow-u p in coh ort stu d ies a n d q u a lity in fo rm a tio n in b o th ca se-con trol an d ecological stu d ies);
• th ey requ ire sign ifican t sam p les, n ot always accessib le in stu d ies on h u m an b ein gs; • eth ical lim itation s m ay con strain th e acqu i-sitio n o f im p o rta n t d a ta , sin ce m a n y in va sive p roced u res are n ot allowed in h u m an b ein gs.
Ca u sa l in feren ce, a cru cia l p o in t in ep id em iological stu id ies, h as b een th e target of n u -m ero u s a tte-m p ts to en su re a relia b le wa y o f lin kin g exp o su re to h ea lth effects. Th is p ro b lem h a s in crea sed sin ce th e first p o p u la tio n -b ased stu d ies were u sed in en viron m en tal an d o ccu p a tio n a l h ea lth . Th e n eed to d istin gu ish b etween ca u sa l a n d n o n -ca u sa l exp la n a tio n led research ers to d efin e a set of cau sal criteria wh ich , on ce satisfied , cou ld assu re th e valid ity o f resu lts. Du rin g th e 1960s, Sir Au stin Hill (1965) p rop osed th e followin g set of criteria: • stren gth of th e association : stron g associa-tio n s, wh ich rem a in sta tistica lly sign ifica n t even a fter co n tro llin g fo r co n fo u n d ers, a re m ore likely to b e cau sal;
• con sisten cy: sim ilar resu lts b ein g ob served b y d ifferen t resea rch ers in d ifferen t p o p u la -tion s an d u n d er d ifferen t circu m stan ces (in th e case of air en viron m en tal ep id em iology, resu lts from LPAE are an alogou s to th ose fou n d in d if-feren t p laces arou n d th e world );
• sp ecificity: a cau se m u st b e associated with a sin gle d isease or grou p of d iseases. Air p ollu -tio n is a sso cia ted with resp ira to r y d isea ses (h owever, air p ollu tan ts h ave also b een associ-a ted with cassoci-a rd iovassoci-a scu lassoci-a r associ-a n d o p h th associ-a lm ic d is-eases);
• tem p o ra lity: exp o su re m u st p reced e th e d isease to rein force cau sal in feren ce;
• b iological grad ien t: th e p resen ce of a d ose-d ep en ose-d en t association b etween exp osu re an ose-d effect, with h igh er exp osu res lead in g to greater effects;
• b io lo gica l p la u sib ility: b a sed o n p revio u s kn owled ge ab ou t b oth th e p ath op h ysiology of th e d isease an d th e m ech an ism s by wh ich p ol-lu ta n ts co u ld lea d to a d verse h ea lth effects. Toxicological stu d ies in an im als h ave h elp ed to u n d erstan d m an y of th ese p rocesses;
• an alogy ju d gm en t: if en viron m en tal p ollu -tan ts in exp erim en tal stu d ies p rove cap ab le of in d u cin g b oth in flam m atory an d im m u n ologca l a ltera tio n s o n th e resp ira to r y tra ct o f a n i-m a ls (Ha tch et a l., 1985; Sa ld iva et a l., 1992; Gilm o u r & Selgra d e, 1993; Devlin et a l., 1994; Lem os et al., 1994), th ey m ay in d u ce sim ilar al-teration s in h u m an b ein gs.
Th e in creasin g im p ortan ce of su ch stu d ies an d th e n eed for glob al in volvem en t in th e is-su e led th e Wo rld Hea lth Orga n iza tio n , th e Un ited Na tio n s En viro n m en ta l Pro gra m , a n d th e Un ited States En viron m en tal Agen cy to d e-velop th e Health an d En viron m en t An alysis for Decisio n Ma kin g, th e so -ca lled H EADLAMP p roject. Th is p roject in itially took in to accou n t th e stu d ies co n d u cted in Accra (Gh a n a ) a n d Sã o Pa u lo (Bra zil), a ssessin g th e q u a lity a n d availab ility of d ata wh ich cou ld b e u sed to in -vestiga te p o ssib le a sso cia tio n s b etween en vi-ron m en tal exp osu re an d h ealth . Based on b oth th is an d oth er acq u ired exp erien ce, a p relim i-n a r y versio i-n o f th e stu d y wa s p u b lish ed ii-n 1994, su m m arizin g an d in d icatin g m ore ap p ro-p riate m eth od ologies in term s of stu d y d esign , d a ta co llectio n a n d a n a lysis, a n d in feren ce. Th e gu id e wa s tested in d evelo p in g co u n tries a n d th e resu lts p u b lish ed in a fin a l versio n in 1996 (WHO, 1996a, 1996b ). Devised to p rovid e th e n ecessary in form ation for d evelop m en t of p u b lic en viron m en tal p olices, estim atin g p os-sib le im p a cts o n h ea lth fro m exp o su re to d if-feren t en viro n m en ta l p o llu ta n ts, th is gu id e co m b in es m eth o d o lo gies fro m su ch field s a s ep id em iology, toxicology, an d related scien ces, d em on stratin g h ow to con vert existin g d ata in -to u sefu l in form ation for su ch estim ates.
On e fa scin a tin g a sp ect o f th is p ro ject is th at, b ased on kn owled ge ab ou t th e h ealth ef-fects of en viron m en tal agen ts d escrib ed p revi-ou sly, it allows on e to establish adequ ate h ealth in d icators for stu d ies in areas with n o p reviou s research exp erien ce. It also exp lain s h ow to u p -grad e th ese in d icators, b ased on d ata th at h ave gen era lly b een co llected fo r o th er p u rp o ses (seco n d a r y d a ta ), in o rd er to in vestiga te a n d q u a n tify p ossib le a ssocia tion s b etween exp o-su re an d h ealth effects. In a o-su b sequ en t step, it a llows o n e to in terp ret th e resu lts p ro p erly, th u s relia b ly reflectin g th e situ a tio n in th e com m u n ity u n d er stu d y.
On e o f th e m a in a im s o f th e H EADLAMP p ro ject is to gen era te su fficien t kn owled ge to su p p ort low-cost, h igh -q u a lity d ecision -m a k-in g. Qu ick an d effective m easu res m ay th u s b e taken , lead in g to a p ositive im p act on su stain -a b le growth -a ro u n d th e p l-a n et, rec-a llin g th -a t su stain ab ility is d efin ed as th e search for b oth
growth a n d d evelo p m en t with o u t risks to th e su rvival of h u m an ity.
A h istorical an alysis of en viron m en tal ep i-d em io lo gica l resea rch a lrea i-d y co n i-d u ctei-d a l-lows o n e to id en tify th e m o st freq u en tly u sed m eth od s: ecological, coh ort, an d to a lesser ex-ten t case-con trol ap p roach es.
Ecological studies
Po p u la tio n -b a sed stu d ies h a ve b een u sed in en viro n m en ta l ep id em io lo gy sin ce even ts in Meu se Va lley, Belgiu m (Firket, 1931), Do n o ra , Un ited States (Ciocco & Th om p son , 1961), an d Lon d on , En glan d (Logan , 1953). Su ch “ecologi-ca l” o r “a ggrega te” a p p ro a ch es u se gro u p s rath er th an in d ivid u als as u n its of ob servation (Mo rgen stern , 1995). Th u s, th e jo in t d istrib u tion of an y com b in ation of variab les at th e in d ivid u a l level (exp o sed ca ses, exp o sed n o n ca ses, u n exp o sed ca ses, a n d u n exp o sed n o n -ca ses) is u n kn own (Fletch er et a l., 1996). Th e an alysis gen erally u ses secon d ary d ata, like th e n u m b er of d eath s, h osp ital ad m ission s, em er-gen ce ro o m visits, sym p to m s o f sp ecific d is-ea ses, o r va ria tio n in m ed ica tio n o n a d a ily, weekly, or m on th ly basis.
An eco lo gica l stu d y m a y b e cla ssified first a cco rd in g to th e m eth o d u sed to m ea su re p osu re. It is called exp loratory if th ere is n o ex-p osu re of in terest (or it was n ot m easu red ) an d th e ta rget o f th e stu d y is to d efin e th e d isea se b eh a vio r (va ria b le o f in terest), lo o kin g fo r a season al an d / or sp atial p rofile; it is an alytical if th e exp osu re is m easu red an d in clu d ed in th e an alysis an d th e aim is to in vestigate a p ossib le co rrela tio n b etween exp o su re a n d m o rb id effect. It m a y seem stra n ge to p u rsu e ca u sa l in -feren ce in ecological stu d ies (th e p u rists m igh t sa y it is in con sisten t or a b su rd ). However, d e-velo p m en ts in th e a rea s o f stu d y d esign a n d statistical tools to an alyze tim e series h ave led resea rch ers to m a ke stro n g a ssertio n s a b o u t cau sality in th e air p ollu tan t/ d isease relation -sh ip. An a sso cia tio n fo u n d in a n eco lo gica l stu d y th at p roves to b e rob u st, con sisten t, sp e-cific, tem p o ra lly o rd ered , with b o th gra d ien t a n d b io lo gica l p la u sib ility, co h eren t, a n d ex-p erim en ta lly ex-p roven a cco rd in g to th e criteria p rop osed by Sir Au stin B. Hill m ay b e assu m ed as cau sal (Sch wartz, 1994a).
A secon d way of classifyin g ep id em iological stu d ies con sid ers th e m eth od of grou p in g d ata (Mo rgen stern , 1995). In th is ca se it m a y b e id en tified by:
• tim e (tim e-tren d study or tim e-series stu d y), wh ere d isease rates are com p ared over tim e in o n e geo gra p h ica lly d eterm in ed p o p u la tio n . Th is fo rm is less su scep tib le to erro rs th a n m u ltip le-grou p stu d ies;
• p la ce a n d tim e (m ixed stu d y), wh ere ra tes are com p ared am on g m an y region s over tim e. Severa l rea so n s h a ve b een cited fo r th e u se o f ecological stu d ies. To m en tion a few:
• low co st a n d sh o rt tim e fra m e, sin ce sec-o n d a r y d a ta h a ve a lrea d y b een csec-o llected a n d can easily b e arran ged . Su ch is th e case of m or-b id ity a n d m o rta lity d a ta a n d a ir p o llu ta n t m easu rem en ts;
• a d ju stm en t to situ a tio n s wh ere wo rkin g with in d ivid u al m easu rem en ts wou ld b e in ad -equ ate or too exp en sive;
• in terest in ecological effects, wh en p op u latio n in ter ven latio n s, su ch a s ed u ca latio n a l p ro -gra m s, n ew la ws, o r p u b lic p o lices h a ve b een evalu ated .
Sim p licity of both an alysis an d p resen tation were con sidered in h eren t advan tages of ecological stu d ies u n til a d ecad e ago. Som e m eth od -ological p rob lem s are worth m en tion in g: • it is som etim es im p ossib le to d irectly esti-m ate risk th at a given even t will occu r, b ecau se th e rea l d istrib u tio n in sid e th e gro u p is u n -kn own ;
• in d ivid u a l exp o su re m ea su res ca n n o t b e u sed to estim a te gro u p exp o su re, sin ce va ri-ab ility in th e grou p’s exp osu re is u n kn own ; • if m ea n va lu es a re a d o p ted fo r exp o su re, d isea se, a n d o th er cova ria tes, th eir a d eq u a cy for estim atin g in d ivid u al exp osu re is in versely p rop ortion al to th e size of th e area stu d ied .
However, wh en th e in ten t is to stu d y th e as-sociation b etween variab ility in b oth exp osu re a n d d isea se, th e eco lo gica l a p p ro a ch is th e m o st a p p ro p ria te, wh eth er in m u ltip le-gro u p stu d ies, wh ere extern al m igration m ay in d u ce b ias in th e grou p com p arison , or in tim e-series stu d ies, wh ere th e in flu en ce o f co n fo u n d ers m u st b e con trolled . In ou r exp erien ce, season -a l v-a ri-a tio n s -a n d we-a th er h -a ve sh own -a re-m a rka b le ire-m p a ct o n a ir p o llu ta n ts a n d h ea lth in d icators.
A p rim ord ial asp ect th at m u st b e an alyzed is th e la ten cy p erio d b etween exp o su re a n d ou tcom e. It seem s reason ab le to ad m it th at in -d u ctio n o f a -d verse effects ta kes so m e tim e, ra n gin g fro m h o u rs to d a ys, a cco rd in g to th e d ifferen t agen ts an d ou tcom es.
In in d ivid u ally b ased ep id em iological stu d ies, va ria b les su ch a s sm o kin g, a lco h o l co n -su m p tion , h ou sin g con d ition s, an d p reexistin g d isea ses a re co m m o n ly co n tro lled . However, eco lo gica l stu d ies d o n o t co n tro l su ch va
ri-ab les, b ecau se th e freq u en cy in th eir variation is q u ite d ifferen t from th e p ollu tion freq u en cy b ein g stu d ied (Sch wartz, 1994b ).
Develo p m en t o f sta tistica l tech n iq u es fo r eco lo gica l stu d ies m a d e it p o ssib le to co n tro l co n fo u n d ers, u sin g lin ea r a n d n o n lin ea r a p -p ro a ch es, a n d m o re relia b le a sso cia tio n s b e-tween exp osu re an d h ealth h ave b een sh own .
An a ccu ra te p o p u la tio n -b a sed stu d y d e-m a n d s h igh -q u a lity d a ta . Th ese stu d ies h a ve b een u sed m o re freq u en tly in Eu ro p e a n d th e Un ited States, sin ce th ey h ave d ata sets cover-in g lo n g p erio d s o f tim e a n d th e q u a lity o f record in g is excellen t.
On e eco lo gica l stu d y with a m a jo r im p a ct o n t h e scie n t ific co m m u n it y wa s co n d u ct e d b y Po p e III e t a l. (1992). In a p re d o m in a n t ly Morm on com m u n ity, wh ere th e p rop ortion of sm okers was on ly arou n d 5%, an old steel m ill was th e m ain sou rce of air p ollu tan ts, p rod u c-in g so m e 80% o f th e p a rticu la te m a tter c-in th e regio n (p a rticle co n cen tra tio n wa s a b ove th e a ir q u a lity sta n d a rd ). Fo r o n e yea r, wh ile th e p la n t wa s clo sed b y a strike, th e n u m b er o f d eath s d u e to resp iratory d iseases d rop p ed sig-n ifica sig-n tly, co m p a risig-n g th e p erio d s b efo re a sig-n d a fter th e strike. Th ese resea rch resu lts h elp ed call for a review of air qu ality stan d ard s.
Cohort studies
Coh ort stu d ies in volve su b jects from well-d e-fin ed sa m p les th a t ca n b e fo llowed fo r so m e p eriod of tim e, ob servin g:
• clin ical sign s an d sym p tom s of resp iratory d isea ses su ch a s co u gh , wh eezin g, a n d fre-qu en cy of m ed ication in com p arison to air p ollu ta n t levels, co n tro lled fo r clim a tic a n d sea -son al con fou n d in g factors.
• p u lm o n a ry fu n ctio n tests, recru itin g in d i-vid u als for a coh ort stu d y, evalu atin g d aily p u l-m on ary cap acity tests by p erforl-m in g p eak flow, co m p a red to d a ily a ir p o llu tio n , tem p era tu re, an d h u m id ity d ata.
Tim e of exp osu re is a relevan t asp ect wh en stu d yin g th e effects o f a ir p o llu tio n . Acu te ep iso d es a n d ch ro n ic exp o su re to a ir p o llu -tan ts sh ou ld b e an alyzed by d ifferen t m eth od s. On e ca n th u s d ivid e ep id em io lo gica l stu d ies in to ch ron ic an d acu te exp osu res. Coh ort stu d -ies h a ve b een a kin d o f go ld sta n d a rd in en vi-ron m en tal ep id em iology, sin ce th ey d eal with risk from exp osu re to air p ollu tion in large u r-b an areas. Th ey h ave r-b een u sed sp arin gly d u e to th eir h igh cost an d lon g-term follow-u p.
Per-h ap s tPer-h e m ost im p ortan t researcPer-h Per-h as been tPer-h at p erfo rm ed b y Do cker y et a l. (1993), in wh ich n early 8 th ou san d in dividu als were followed for alm ost 16 years. Card iop u lm on ary risk factors like sm o kin g, a lco h o lism , seru m ch o lestero l, sch oolin g, gen d er, an d age were m on itored in 6 Am erica n cities with sim ila r socioecon om ic co n d itio n s b u t d ifferen t a vera ge co n cen tra -tion s of p ollu tan ts, m ain ly total su sp en ded p articulate. The study showed a lower life exp ectan -cy in cities with h igh er air p ollu tion levels.
Bo th p ro sp ective co h o rt stu d ies a n d o n es like th at q u oted ab ove req u ire m illion s of d ol-lars in fu n d in g, d u e to b oth th e n u m b er of p eo-p le in volved in eo-p eriod ic d ata collection an d th e h u ge n u m b er o f la b o ra to r y tests n eed ed to con trol several variab les in each stu d y su b ject. Retro sp ective co h o rt stu d ies, wh ich d em a n d less tim e a n d m o n ey, sh ow n o a d va n ta ge a s com p ared to ecological stu d ies in term s of elu -cid atin g th e relation sh ip b etween air p ollu tion an d its ad verse h ealth effects. Su ch ep id em iol-o gists a s Jiol-o el Sch wa rtz a n d Diol-o u gla s Diol-o cker y, fro m th e Ha r va rd Un iversity Sch o o l o f Pu b lic Hea lth , a n d C. Ard en Po p e III, fro m Brigh a m You n g Un iversity, h ave con sisten tly su p p orted th is p oin t of view.
Case-control studies
Th is kin d o f stu d y is u sed fo r ra re d isea ses a s com pared to an other select con trol group, in ves-tigatin g th e p ossib le origin of exp osu re for th at disease. Th e ap p roach h as been u sed to observe ad verse even ts d u rin g th e h u m an rep rod u ction p rocess, su ch as fetal d eath an d con gen ital ab -n orm alities, as well as i-n occu p atio-n al d iseases like p n eu m ocon iosis, can cer, an d h eavy m etal p oison in g (Sad a-Cieslar et al., 1994; Takah ash i et al., 1994; Can tor et al., 1995; Liou et al., 1997). Research com p arin g several typ es of can cer an d en viron m en tal exp osu re with n o occu p ation al relation ship also em ploy this m ethod (Feychtin g et al., 1998; Lagard e & Persh agen , 1999).
Qu ality of d ata an d p rop er h an d lin g of th e stu d y a re of grea t im p orta n ce for esta b lish in g criteria for selectin g grou p s of in terest, estab -lish in g a p recise d iagn osis, an d facilitatin g col-lection of retrosp ective d ata from th ese grou p s. Th is m od el h a s b een u sed in en viron m en -tal research to evalu ate p ossib le ad verse effects of air p ollu tion on th e resp iratory system , esp e-cially in in d oor en viron m en ts, wh ere th e large n u m b er o f p o ssib le b ia ses ca n b e co n tro lled ad equ ately, u n like ou td oor en viron m en ts.
Som e ad van tages of th is typ e of stu d y (Fen -ster et al., 1991):
• low co st a n d sh o rter tim e fra m e a s co m -p a red to a ltern a tive stu d ies, su ch a s -p ro s-p ec-tive coh orts;
• wh en u sed to ob serve d iseases with a sh ort laten cy p eriod (stu d ies on fetal m alform ation , fetal d eath , acu te resp iratory d iseases, an d in -d oor p ollu tion ), risk of m em ory b ias is m in or.
LPAE epidemiological studies
Ep id em iological stu d ies con d u cted at th e LPAE h a ve b a sica lly o b ser ved th e a sso cia tio n b e-tween m orb id ity-m ortality an d air p ollu tion in th e city of São Pau lo.
Mortality d ata in São Pau lo cover an exten -sive tim e p eriod an d con stitu te a reliable sou rce of in form ation for ep id em iological stu d ies.
Data on weath er an d con cen tration of vari-ous air p ollutan ts were collected from a n etwork con sistin g of several m on itorin g station s from various p arts of the city. Data quality varied over tim e becau se of th e equ ip m en t’s rap id obsoles-cen ce a n d la ck of in vestm en t in th is m on itor-in g n etwork a d m itor-in istered by CETESB a n d th e In stitu te of Geop h ysics an d Astron om y (IAG).
Th e m orb id ity d ata in ou r stu d ies were tak-en fro m a m o n ito rin g system sp ecifica lly d e-sign ed to ad m in ister costs in th e p u b lic h ealth system . Th e data’s u sefu ln ess was lim ited, sin ce variou s classes of in form ation were in ad equ ate or im p rop erly classified an d m igh t th u s gen er-ate con fu sion d u rin g an alysis.
Air p ollu tion is d ifficu lt to a void , sin ce th e air layer su rrou n d in g th e b iosp h ere is con tin u -o u s a n d c-o n sta n tly m -ovin g. Sim p le b rea th in g is th e m ost effective exp osu re rou te. Th e m ost com m on a d verse h ea lth effects a re in th e res-p iratory an d card iovascu lar system s, affectin g ch ild ren an d th e eld erly m ore freq u en tly th an oth er age grou p s.
Severa l stu d ies o n th e effects o f a ir p o llu -tion on h ealth h ave estim ated correla-tion s an d a d ju stm en t o f gen era lized lin ea r m o d els in -vo lvin g sim p le a n d m u ltip le lin ea r regressio n m od els, logistic an d Poisson , b esid es an alysis o f va ria n ce (McCu lla gh & Neld er, 1989; Do b -son , 1990). On e of th e m ain ad van tages of th is grou p of m od els is th at th ey can b e u sed in sit-u a tio n s wh ere th e resp o n se va ria b le fo llows n on -n orm al d istrib u tion s or its relation sh ip to th e exp la n a to r y va ria b les is n o n -lin ea r. Th e target variab le is gen erally on e of th e h ealth in -d icators. Th ese rep resen t th e n u m b er of tim es a sp ecific even t occu rs (e.g., d eath s or h osp ital ad m ission s) d u rin g a u n it of tim e d eterm in ed b y th e resea rch er (d a y, week, m o n th , etc.). Th ese cou n ts gen erally follow Poisson d istrib u tion wh en it is com m on to u se regression m od -els in vo lvin g th is typ e o f d istrib u tio n . Use o f th is regression m od el also h as th e ad van tage of a llowin g fo r estim a tio n o f th e rela tive risk, wh ich is h igh ly u sefu l for evalu atin g th e im p act of p ollu tion on th e p op u lation’s h ealth (Klein -b a u m et a l., 1998). Th e Po isso n regressio n m od el can b e d escrib ed as follows:
ln [E( Yj)] = p
Σ
Xjβj j = 1in wh ich ln is th e n atu ral logarith m ; E( Yj )is th e n u m b er o f exp ected a d m issio n s o r d ea th s o n th e jthd ay; Xj(j = 1,...,p ) corresp on d to th e p
ex-p lan atory variab les ob served on th e jthd ay (for
in stan ce, tem p eratu re, p ollu tion ) an d βjare th e
p aram eters on e wish es to estim ate an d th rou gh wh ich o n e sh o u ld eva lu a te th e effects o f ea ch exp la n a tory va ria b le on th e exp ected n u m b er of ad m ission s or d eath s.
In ord er to ob tain p lau sib le resu lts it is im -p ortan t to n ote th at th e association on e wish es to ch aracterize m ay b e in flu en ced by a series of fa cto rs wh ich ca n co n fo u n d o r in va lid a te th e resu lts. Th ese factors can in clu d e th e p resen ce o f tren d s a n d sea so n a lity, co n fo u n d in g va ri-ab les (su ch as tem p eratu re an d h u m id ity), lags b etween ca u se a n d effect, a n d p o ssib le a u to -co rrela tio n b etween o b ser va tio n s m ea su red over tim e an d oth ers (Pop e III & Sch wartz, 1996; Sch wartz et al., 1996). Con cern in g th e p ossib le existen ce of au tocorrelation b etween ob serva-tion s record ed over tim e, th e literatu re p rop os-es sta tistica l tech n iq u os-es to in co rp o ra te th is ch a ra cteristic, a m o n g wh ich th e Zeger m o d el for cou n ts series an alysis (Zeger & Lian g, 1986). Th e m od el sh ou ld con ta in , a s exp la n a tory variab les, th e p ollu tan t con cen tration , con trols fo r sea so n a lity (th e u su a l a p p ro a ch es a re th e in clu sio n o f in d ica to r va ria b les fo r m o n th s o f th e year or m on th s of th e stu d y p eriod , th e u se o f sin e a n d co sin e term s o r n o n -p a ra m etric
fu n ction s, d ay of th e week an d h olid ay in d ica-tors), tem p eratu re, an d h u m id ity fu n ction s.
Mo d els in vo lvin g n o n -p a ra m etric fu n c-tion s, called gen eralized ad d itive m od els, were p ro p o sed b y Ha stie & Tib sh ira n i (1990) a n d were recen tly a d o p ted in th e a n a lysis o f th is typ e of d ata. Th ese m od els p roved h igh ly u se-fu l n o t o n ly to co n tro l sea so n a lity a n d tren d s b u t also in m od elin g th e relation sh ip b etween m orb id ity an d m ortality m arkers an d weath er va ria b les (tem p era tu re a n d h u m id ity), wh ich can b e n on -lin ear.
Co n cern in g th e la g b etween ca u se a n d ef-fect, it is reason ab le to con sid er th at th e effect of exp lan atory variab les (tem p eratu re, h u m id i-ty, p ollu tion , etc.) on h ealth in d icators d oes n ot n ecessarily occu r on th e sam e d ay of th e target even t (a d m issio n o r d ea th ). Th a t is, th e n u m -b er of ad m ission s or d eath s on a given d ay can b e a co n seq u en ce o f wea th er co n d itio n s a n d p ollu tion on b oth th e con cu rren t an d p reviou s d ays. A sim p le ap p roach to exam in e th e con tri-b u tion of su ch factors over th e cou rse of sever-a l d sever-a ys is th e u tilizsever-a tion of m od els con tsever-a in in g la gs o r m ovin g a vera ges fo r wea th er va ria b les an d p ollu tan t con cen tration s. Mod els with d if-feren t lags n eed to b e in vestigated .
Final remarks
Th e st u d ie s p e r fo r m e d b y t h e LPAE a re co n sist e n t wit h t h o se o f o t h e r re se a rch e rs, d e sp it e h a vin g d iffe re n t p o llu t a n t co n ce n t ra -tion s, d isp ersion , an d socioecon om ic ch arac-teristics. Th e resu lts su p p ort a con sen su s th at a ir p o llu t io n is h a r m fu l t o t h e p u b lic h e a lt h , m ain ly for th e grou p s con sid ered su scep tib le, b u t a lso for th e p op u la tion a t la rge. Th ey a lso in d icate th at th ese effects occu r even if p ollu -t a n -t co n ce n -t ra -t io n s a re b e low -t h e p re va ilin g legal lim its.
In th e ca se o f th e city o f Sã o Pa u lo, wh ere air p ollu tion is closely lin ked to m obile sou rces, d ecrea sin g th e im p a ct o n h ea lth d em a n d s a n overh a u l in th e u rb a n tra n sp o rta tio n d esign , in clu d in g ration al p lan n in g of th e tran sp orta-tio n system , resea rch o n a ltern a tive fu els, a d o p tio n o f less p o llu ta n t tech n o lo gies, a n d im p lem en tation of a p u blic awaren ess p rogram on air p ollu tion’s ad verse effects.
Figu re 1 sh ows th e resu lt o f o u r stu d ies in term s o f th e rela tive risk fo r m o rb id ity a n d m o rta lity, co n sid erin g five p o llu ta n t co n cen -tration categories for São Pau lo city.
In sh o rt, th e co n tin u o u s en h a n cem en t o f statistical tools allows u s to in crease th e p reci-sion of ou r a n a lyses, b u t th is ga in ca n on ly b e effectively reflected in ep id em io lo gica l re-search resu lts if d ata q u ality is im p roved . Su ch d ata sou rces in clu d e:
• m orb id ity an d m ortality record s;
• in form ation from th e en viron m en tal m on i-torin g system ;
• rea d ily a va ila b le reco rd s in th e electro n ic m ed ia for im m ed iate con su ltation .
All th ese will en ab le u s to su p p ort relevan t d ecision -m akin g to estab lish accep tab le em is-sion s stan d ard s an d p ollu tion exp osu re lim its, in sta ll a n effective en viron m en ta l system fosterin g th e im p lem en ta tio n o f a va lid en viro n -m en ta l p o licy (with co n tin u o u s d evelo p -m en t an d im p rovem en t), an d u n d ertake sou n d m an -a gem en t p rin cip les in th e p l-a n n in g, im p lem en ta tio n , co n tro l, a n d a d ju stlem en t o f lem ea -su res with a view towa rd s b etter re-su lts with lower costs an d in a sh orter tim e fram e.
We aim to lin k the results of scien tific kn owl-ed ge to th e n eowl-ed s o f a so ciety wh ich seeks to im p rove its econ om ic an d social stru ctu res an d ach ieve a su stain ab le d evelop m en t m od el th at m in im izes h arm to b oth h u m an b ein gs an d th e en viron m en t.
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