J. Pneumologia vol.25 número5

J Pneumol 25(5) – set-out de 1999

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Poluição e doenças ocupacionais pulmonares

Poluição e doenças ocupacionais pulmonares

EDUARDO ALGRANTI1

COMENTÁRIOS E RESUMOS

Foram apresentados quatro trabalhos sobre Doenças

Ocu-pacionais Pulmonares, sendo dois experimentais e dois

clíni-cos, e cinco trabalhos sobre Poluição, sendo três

experimen-tais e dois epidemiológicos.

D

O

P

Os trabalhos experimentais de DOP são do grupo do

La-boratório de Fisiologia Respiratória da UFRJ e referem-se

ao estudo da caracterização das p rop riedades mecânicas

pulmonares em pulmões de ratos, 2 0 dias após injeção

in-tratraqueal de sílica, comparada com injeções de soro

fisioló-gico (Silva GH e col.). Um segundo trabalho aborda os

meca-nismos celulares implicados nas alterações funcionais,

com-parando-se ratos normais com uma linhagem de ratos

defi-cientes em CD9 5 (Falcão H e col.).

No presente, há uma relativa pobreza em trabalhos que

procurem desvendar os mecanismos patogênicos das

altera-ções conseqüentes à exposição à sílica. O principal motivo

prende-se à relativa perda de interesse em países

desenvolvi-dos, pelo fato de a silicose não ter importância

epidemiológi-ca de anos passados. Porém, no Brasil, a situação é diversa,

sendo a silicose a pneumoconiose mais prevalente. O estudo

dos mecanismos celulares implicados no processo da doença

é um dos caminhos que podem indicar possibilidades

tera-pêuticas, fato de grande relevância. Ratos deficientes em Fas

(CD9 5 ) não apresentavam alterações histopatológicas e/ ou

mecânicas do tecido pulmonar. Ratos não deficientes

apre-sentaram infiltrações neutrofílicas, obstruções

intrabrônqui-cas e atelectasias, que se traduziam funcionalmente por um

aumento da resistência elástica pulmonar. Estes fenômenos

são precoces e, possivelmente, compatíveis com exposições

humanas a altas concentrações de sílica.

Os trabalhos clínicos são familiares aos pneumologistas

interessados na área, pois haviam sido apresentados no

últi-mo Congresso Brasileiro. O tema de avaliação das trocas

gasosas, em repouso e exercício em pacientes portadores de

asbestose apresentado pelo Grupo Interinstitucional de

Estu-dos das Doenças Associadas ao Asbesto (Unicamp, USP,

Unifesp) (Sette AA e col.) é de grande importância na

avalia-ção da disfunavalia-ção e incapacidade. O Laboratório de Exercício

da Unifesp, já há anos, contribui para um melhor

entendi-mento destas questões. O DLCO não costuma estar afetado

nas fases iniciais da asbestose, porém não há dados no

resu-mo que correlacionem as trocas gasosas com a leitura

radio-lógica ou os achados tomográficos. Interessante que apenas

5 0 % dos casos com DLCO de repouso alterado

apresenta-vam o aumento na diferença (A-a) O

de repouso e exercício.

Uma maior amostragem, com controle para as variáveis de

confusão, certamente será um excelente contribuição para

um melhor estabelecimento da disfunção associada à

asbes-tose.

Aspectos ligados à inflamação de vias aéreas na exposição

a sílica foram abordados pelo grupo de Pneumologia da UFRJ

(Lago P e col.). Foram obtidas amostras de escarro induzido

de 3 3 trabalhadores de pedreira e 9 controles.

Trabalhado-res e controles incluídos na análise não apTrabalhado-resentavam asma,

infecções respiratórias recentes e não eram fumantes. Dos

3 3 , 1 3 eram administrativos e 2 0 da área de produção. A

neutrofilia de escarro foi significativamente maior nos

traba-lhadores comparados com os controles, porém,

inesperada-mente não houve diferença entre trabalhadores da área

ad-ministrativa e os da área de produção. Trabalhadores com

mais tempo de atividade apresentavam maior neutrofilia no

escarro. A sinalização de uma associação entre neutrofilia no

escarro e tempo de exposição merece ser melhor explorada.

P

Os trabalhos sobre Poluição seguem uma linha de

pesqui-sa sólida iniciada pelo Laboratório de Poluição Experimental

do Ar da FMUSP.

Os trabalhos experimentais abordaram o estresse

oxidati-vo das PM

sobre o epitélio de palato de sapos (Macchione

M e col.) e o efeito do formaldeído no transporte mucociliar

(Fló-Neyret C e col.). Através da análise de mucinas e

gluta-thion, demonstrou-se que a exposição a PM

associa-se a

um significativo efeito oxidativo sobre o epitélio ciliado,

as-sim como o formaldeído, em concentração crescente,

asso-ciou-se a uma diminuição do transporte mucociliar em

pre-parações de palato de sapos. Ambos tratam de efeitos

agu-dos agu-dos poluentes nas vias aéreas que, nem sempre, podem

ser extrapolados para situações clínicas de exposições

conti-nuadas, uma vez que há mecanismos de balanço que se opõem

ao efeito deletério dos poluentes.

Algranti E

242

Um trabalho interessante apresentado pela Unifesp sobre

o efeito da conservação de muco humano em diferentes

tem-peraturas mostra que ele não perde suas propriedades

(velo-cidade de transporte) quando conservado a um temperatura

próxima ao ambiente (Gastaldi AC e col.).

A influência da exposição a poluentes ambientais em

ad-missões por doença coronariana isquêmica em um hospital

especializado da região urbana de São Paulo foi avaliada em

um período de dois anos (1 9 9 4 -1 9 9 5 ) (Lin CA e col.).

Atra-vés de técnicas de regressão, demonstrou-se ser o CO o

po-luente que melhor explica a associação com um aumento de

admissões hospitalares, sem apresentar o chamado “limiar

de exposição”, ou seja, um limite abaixo do qual não se

ob-servam influências com o evento de estudo. O mecanismo

de ação do CO no aumento da morbidade coronariana

pren-de-se à diminuição da oferta de oxigênio ao músculo

car-díaco.

Em outro estudo epidemiológico, com metodologia

seme-lhante, acompanhou-se uma coorte de 1 0 7 crianças

asmáti-cas (6 -1 7 anos) por um período relativamente curto (um a

dois meses?), através de medidas diárias do pico de fluxo

expiratório (PFE) e sintomas (Cabral AL e col.). O PEF

asso-ciou-se negativamente ao poluente O

sem demonstrar

efei-tos diferenciados entre os subgrupos de diferentes

gravida-des de asma. Não há menção de associação entre poluentes

e sintomas. Este trabalho foi realizado na zona urbana de

São Paulo, onde predomina a poluição a material

particula-do. O O

é um potente irritante de vias aéreas e associa-se a

um aumento das reatividade brônquica em suscetíveis,

po-rém, outros gases como o SO

e NO

também atuam como

irritantes. Possivelmente associações distintas entre os

diver-sos poluentes que ocorrem de maneira sazonal dentro de

uma mesma área podem gerar diferentes modelos de

asso-ciação com os efeitos sobre as vias aéreas.

ASSOCIATION BETWEEN AIR POLLUTION AND CARDIOVASCU-LAR ADMISSIONS IN SÃO PAULO, BRAZIL.

Lin CA, Braga ALF, Conceição GMS, Pereira LAA, Kishi HS, Milani J r. R, Saldiva PHN. Laboratory of Exp erimental Air Pollution, School of Medicine, University of São Paulo, SP, Brazil.

This work focuses the relation between air p ollution and hosp ital admissions due to ischemic cardiovascular illness (angina and acute heart infarction – ICI) in São Paulo City. Daily records of hosp ital ad-missions for p eop le between 4 5 and 8 0 years were obtained from the Heart Institute of the University of São Paulo Medical School, from J anuary 1 9 9 4 to December 1 9 9 5 . Daily measures of CO, SO2, PM1 0

and ozone were obtained for the same p eriod from the State Air Pol-lution Controlling Agency (Cetesb) as well as weather variables ob-tained from Institute of Astronomy and Geop hysics of the University of São Paulo. The analysis was made by Poisson regression techniques, controlled of time trend, weather and days of week. CO (2 -days mov-ing average) was the p ollutant that exhibited the most robust associa-tion with cardiovascular admissions. The average levels of CO during the study (5 .2 p p m) were associated with 6 % increase of ICI. This

association exhibited a linear behavior and did not disclose any evi-dence of safety threshold. The results of this study sup p ort the idea that air p ollution p romotes significant health effects in São Paulo.

GAS EXCHANGE ABNORMALITIES AT REST AND DURING EX-ERCISE IN PATIENTS WITH ASBESTOSIS.

Sette AA, Guimarães SML, Bagatin E, Terra Filho M, Rodrigues RT, Kawakama J I, Nap oli L, Nery LE. Interinstitutional Group of Study of Asbestos Related Disorders – Unicamp , USP, Unifesp , São Paulo, Bra-zil.

In order to evaluated p ossible gas exchange abnormalities in p a-tients with asbestosis, we obtained lung diffusion capacity (DLCO and DLCO/ VA) and arterial blood gases at rest and during constant load submaximal exercise (bellow the lactate threshold). Seventeen male workers, 4 0 to 8 2 years old, of the fibrocement industry were studied. The diagnosis of asbestosis was based in the occupational history, chest X-ray (ILO, 1 9 8 0 ) and high resolution comp uted tomograp hy. Seven p atients had altered sp irometry (6 with obstructive dysfunction), and 5 of them were current smokers. By contrast, 9 of 1 0 p atients with nor-mal sp irometry were non smokers or ex-smokers (2 test, p = 0 .0 1 ). We did not observe PaCO2 change, but reduction of PaCO2 was

de-tected in 5 and increase of P(A-a)O2 (> 5 mmHg) in 7 patients, during

exercise. Also, DLCO was reduced in 6 subjects, but just three of them had concomitant P(A-a)O2 increase (2 test; p = 0 .3 0 NS). We conclude

that in p atients with asbestosis, DLCO at rest and variation of P(A-a) O2 from rest to exercise are useful tests for the diagnosis of gas

ex-change abnormalities; however DLCO was not always p redictive of such abnormalities. Other factors p ossibly imp licated are: increase of areas of low, ventilation/ p erfusion (V/ Q) and/ or reduction of PvO2 in

areas of low V/ Q, during exercise.

EVALUATION OF BRONCHIAL INFLAMMATION IN QUARRY MINE WORKERS IN RIO DE J ANEIRO BY INDUCED SPUTUM.

Lago P, Flores V, Ribeiro C, Araújo A, Lemle A, Lapa e Silva J R. Multidisciplinary Laboratory and Pulmonary Medicine Service, Clemen-tino Fraga Filho University Hosp ital, Federal University of Rio de J a-neiro, Brazil.

J Pneumol 25(5) – set-out de 1999

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Poluição e doenças ocupacionais pulmonares

PULMONARY MECHANICS, HISTOPATHOLOGY AND LYMPHO-CYTE APOPTOSIS IN A MURINE MODEL OF SILICOSIS.

Falcão H , Leite-J únior J H P, Ciminelli PB, Borges VM, Lop es MF, DosReis GA, Rocco PRM, Zin WA. Laboratories of Resp iration Phy-siology and Immunology Biology, Carlos Chagas Filho Biop hysics Ins-titute, Federal University of Rio de J aneiro, RJ , Brazil.

Pulmonary mechanics and histop athology from BALB and BALb. GLD [deficient in functional Fas (CD9 5 ) Ligand] mice were analyzed 1 5 days after intratracheal instillation of saline or silica [2 0 mg p er mouse]. Mice were ventilated with constants’ flow and volume, and PEEF (2 cmH2O). Static (Est) and dynamic (edyn) elastances resistive

(P1 ) and viscoelastic/ inhomogeneous p ressures (P2 ) were obtained. In BALB group , Est, Edyn, P1 and P2 increased (3 1 %, 3 7 %, 4 2 1 % and 8 1 %, resp ectively) in relation to saline group . In addition, histologic evaluation revealed interstitial and alveolar edema, accumulations of cells mainly p olymorp honuclear, alveolar collap se and intrabronchial cellular infiltration obstructing the lumen. However, in BALB. GLD, we observed no changes in p ulmonary mechanics and histop athology. Pulmonary BALB lymp h nodes were enlarged, containing increased numbers of macrop hages and activated CD4 + and CD8 + T cells, by flow cytometry. Treating p ulmonary lymp h node cells with anti-TCR; CD3 resulted in CD4 + , but not CD8 + T-cell death, and in DNA frag-mentation. We conclude that silica inhalation led to elastic, resistive and viscoelastic p ulmonary changes that are related to neutrop hil infil-tration, intrabronchial obstruction and alveolar collap se in mouse lung. There was immune stimulation and activation-induced cell death of CD4 + T lymphocytes draining silica-laden macrophages. The Fas/ FasL death p athway ap p ears critically involved in induction of p ulmonary tissue damage.

MECHANICAL BEHAVIOR AND STRUCTURAL COMPOSITION OF LUNG PARENCHYMAL STRIP IN A MURINE MODEL OF SILICO-SIS.

Silva GH, Faffe DS, Kurtz PMP, Rocco PRM, Zin WA. Laboratory of Resp iration Physiology, Carlos Chagas Filho Biop hysics Institute, Fe-deral University of Rio de J aneiro, Brazil.

Recently, mice have been extensively used to investigate the p atho-genesis of silicosis because appropriate murine models are being in-creasingly develop ed. However, the dynamic p rop erties of normal and silicotic mouse lung tissue, characterized by p arenchymal strip s stud-ies, have not been p reviously p erformed. Resistance (R), elastance (E) and hysteresivity (η) were analyzed during sinusoidal oscillations of BALB/ c mice (2 5 -3 0 g) p arenchymal strip s 1 5 days after intratracheal instillation of saline [C, (5 0 µg)] or silica [Sil, (2 0 mg p er mouse)]. In addition, tissue strip s were examined morp hometrically in order to determine its anatomic constitution (the relative amounts of small ves-sels, airways, and alveolar walls) and cellularity. Strips (1 0 x 3 x 3 mm) were cut from the subpleural edge of the left lung. The wet weight and unstressed resting length (Lo) of each strip s were recorded. The strip s were susp ended in an organ bath filled with Krebs solution bubbled with 9 5 %O2-5 %CO2, and maintained at 3 7 º C. One end of the strip

was attached to a force transducer and the other end to a lever system that effected length changes. The strip s were oscillated at resting ten-sion, amplitude of 5 %Lo, and various frequencies (0 .0 3 , 0 .1 , 0 .3 , 1

and 3 Hz). On the basis of tension vs length curves, E, R, and η were comp uted. At the end of the exp eriment, the strip s were fixed in Car-noy at resting tension. Among Sil and C strip s, E increased linearly with the logarithm of frequency, whereas R decreased hyp erbolically with frequency. η was significantly higher at 0 .0 3 Hz, remaining unal-tered with increasing frequencies. Sil strip s p resented R and E higher than C, indep endently of frequency. η was similar in both groups. Sil and C strip s had similar anatomic constitution. Cellular infiltration in Sil strip s correlated with functional changes.

P

ACUTE EFFECTS OF INHALABLE PARTICLES ON MUCOCILIARY EPITH ELIUM.

Macchione M, Oliveira AP, Gallafrio CT, Muchão FP, Obara MT, Guima-rães ET, Artaxo P, King M, Lorenzi-Filho G, J unqueira VCB, Saldiva PHN. Laboratory of Exp erimental Air Pollution, School of Medicine, Physics Institute, Chemistry Institute, University of São Paulo, Brazil, Pulmonary Research Group , Dep artment of Medicine, University of Alberta, Edmonton, Canada.

This work was designed to evaluated by different p arameters the toxicity of inhalable p articles (PM1 0) collected from the urban air in São

Paulo, Brazil, to the mucociliary ap p aratus using the frog p alate p rep -aration. Two group s of frog p alates were immersed in Ringer (control) and 5 0 0 µg/ m3 _{of PM}

1 0 diluted in Ringer during 1 2 0 minutes were

studied by means of morp hometric analyses (quantification of the amount of intraepithelial and surface mucins), measurement of cilia beat frequency (CBF) and quantification of total glutathione (GSH ). Exp osure to PM1 0 elicited a significant dep letion of neutral

intraepithe-lial mucins (NM) (p = 0 .0 4 6 1 ), and decrease of GSH (p = 0 .0 0 3 ). These results showed that PM1 0 can p romote significant alterations in

ciliated epithelium in vitro. These effects are at least in part mediated by oxidative stress.

THE INFLUENCE OF TEMPERATURE AND LENGTH OF TIME OF STORAGE OF NORMAL HUMAN MUCUS SAMPLES ON TRANS-PO RT.

Gastaldi AC, Zanchet RC, J ardim J R. Physiotherapy Graduation Course of Centro Universitário do Triângulo, Resp iratory Division of Federal University of São Paulo, Brazil.

Introduction: frozen stored human mucus have been extensively used for transp ort studies. It was demonstrated for frog mucus, but for hu-man mucus there is no clear evidence of the influence that the temp er-ature and length of time of storage may have on the results. Methods: we collected mucus from endotracheal tube from 1 5 subjects without pulmonary disease and stored their mucus samp les at minus 2 0 and 1 8 º C and analyzed them on days zero and 9 0 . We studied the relative transp ort velocity on frog p alate and contact angle measurements. Results: the means for relative transp ort velocity and contact angle were 1 .1 6 and 2 8 degrees for fresh samples (day zero). At the 9 0th

day, the means were 0 .9 7 and 2 9 degrees for minus 8 0 º C and 0 .9 9 and 2 9 degrees for minus 2 0 º C. Analysis of variance did not show any significance among days or temp eratures (p < 0 .0 5 ). Conclusion: we conclude that normal human mucus can be stored at minus 2 0 or 8 0 º C for a p eriod up to 9 0 days without difference for ciliary transp ort or contact angle measurement.

THE EFFECTS OF FORMALDEHYDE ON THE CILIATED EPITHE-LIUM.

Fló-Neyret C, Lorenzi-Filho G, Saldiva PHN. Dep t. of Pathology, Uni-versity of São Paulo, Federal UniUni-versity of São Paulo, Brazil.

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244

and 6 0 min. After 6 0 min both MT and CBF decreased significantly in the group s 2 .5 and 5 p p m (p < 0 .0 5 ). We conclude that formaldehyde affects, at relatively low concentrations, the clinical mucosa after short term exp osures.

ASSO CIATIO N BETWEEN AIR P O LLUTIO N AND P EAK FLO W MEASUREMENTS IN CHILDREN IN SÃO PAULO, BRAZIL. Cabral AL, Conceição GMS, Pop e CA III, Saldiva PHN, Martins MA. Laboratory of Exp erimental Air Pollution, School of Medicine, Univer-sity of São Paulo, Brazil.

The p resent investigation was designed to evaluate the p ossible as-sociation between urban levels of air p ollution and decrement of p ul-monary function in asthmatic children. For this p urp ose, a cohort study was p erformed involving 1 0 7 asthmatic children, aged 6 to 1 7 years, attending a referral center for asthma management in São Paulo. They were followed from May to J une, 1 9 9 5 . Daily values of O3 (maximum

hourly level), CO (maximum 8 hours moving average), SO2, NO2 and

inhalable particles (PM1 0) (2 4 hours mean) were obtained from 1 2 air

p ollution measuring stations, disp ersed across the town. In addition, daily measurements of temp erature and relative humidity were collect-ed for the same p eriod. Peak exp iratory flow (PEF) measurements (morning and evening), and asthma symp toms were recorded daily for each child in a diary. The relationship between PEF and p ollution was investigated by time series modeling, taking into account not only p ol-lution levels but also different p ossibilities for weather and seasonal effects. Statistical calculations were done using the autoregressive p ro-cedure of the SAS p ackage. PEF was negatively associated with O3

levels up to the p receding 5 days. In average, we observed a decre-ment of 0 .0 8 (standard error of 0 .0 2 5 8 ) liters.s–1 _{for each µg.m}–3 _of

ambient O3, or, in other words, a decrement of 2 .8 liters

–1 _{if one}

con-siders the mean O3 levels (3 4 .4 ug.m

–3_{) observed in São Paulo during}

the p eriod of study. The effects of O3 on PEF were not affected by the