Document X7G2qD6eMDb7vJodwzMxBrZwx

Scand J Work Environ Health 13 (1987) 505-512 Effects of exposure to vehicle exhaust on health by Ulf Ulfvarson, TechD,' Rolf A l e x a n d e r s s o n , MD,* Leif Aringer. MD,3 Eva S v e n s s o n , MD,2 Goran H e d e n s t i e r n a , MD,4Christer H o g s t e d t , MD,'. Bo Holmberg, PhD,3 G u n n a r Ros&~,~ Maria Sorsa, PhD5 ULFVARSON U. ALEXANDERSSON R. ARINGER L. SVENSSON E, HEDENSTIERNA G. HOGSTEDT C, HOLIMBERG 8 , ROSEN G. SORSA .M. E f f m s of exposure to vehicle exhaust on health. %and J Work Environ Health 13 (1987) 505- 512. Exposure to combustion engine exhaust and its effect on crews of roll-on roll-off ships and car ferries and on bus garage staff were studied. The peak concentrations recorded for some of the substances studied were as follows: total particulates (diesel only) 1.0 mg/m', benzene (diesel) 0.3 mg/m', formaldehyde (gasoline and diesel) 0.8 mg/m'. and nitrogen dioxide (diesel) 1.? mg/'m'. The highest observed concentration of benzo(a)pyrene was 30 ng/m' from gasoline and diesel exhaust. In an experimental study volunteers were exposed to diesel exhaust diluted with air to achieve a nitrogen dioxide concentration of 3.8 mg/m'. Pulmonary function was affected during a workday of occupational exposure to engine emissions, but it normalized after a few days with no exposure. The impairment of pulmonary function was judged to have no appreciable, adverse, short-term impact on individual work capacity. In the experimental exposure study, no effect on pulmonary function was observed. Analyses of urinary mutagenicity and thioether excretion showed no sign of exposure to genotoxic compounds among the occupationally exposed workers or among the subjects in the experimental study. Kqv terms: engine exhaust. genotoxicity, mutagenicity, pulmonary function, thioethers. e main emission products arising from the com-stion of fuels in engines are water and carbon dioxide. Other components of vehicle exhaust are nitrogen and oxygen (in diesel exhaust), soot (mostly in diesel exhaust), a large number of hydrocarbons, and deriva'tives of hydrocarbons with oxygen and nitrogen, along with carbon monoxide, oxides of nitrogen, and sulfur dioxide (in diesel exhaust). Their Concentrations vary depending on many factors, eg, fuel composition, lubricant composition, engine design, operating temperature, load, degree of engine wear, fuel supply, condition of the system. Occupations with the highest exposure to engine exhaust include mining; stevedoring; work around loading decks and quays: warehouse work with forklift trucks; loading motor vehicles onto car ferries; and work in bus garages, buildings at airports, parking garages, car-testing stations, and automobile repair shops. The purpose of the present study was to investigate the acute effects of exposure to engine emissions o n the respiratory tract. Furthermore, the mutagenicity method was applied to urine io test for exposures to `' The Royal Institute of Technology. Stockholm, Sweden. Department of Owupational Medicine, Karolinska Hospital, Stockholm. Sueden. National Institute of Occupational Health. Solna, Sweden. ` neparrment of Clinical Physiology. Huddinge Hospital, ddinge. Sueden. m u t e of Occupational Health, Helsinki, Finland. Reprint requests to: Dr R Alexandersson. Department of OCcupational 5ledicine. Karolinska Hospital, S-104 01 Stockholm, Sseden. the complex chemical mixtures contained in engine exhaust, since several earlier studies have shown that components in engine exhaust, especially the particulate fraction, are highly mutagenic in experimental systems (28, 29). A review of the literature relevant to this investigation has already been published (32). Subjects and methods Several workplaces producing comparatively heavy exposure. to diesel exhaust in particular, were chosen for the investigation. (See tables 1 and 2.) Occupational hygiene measurements were carried out at these workplaces, along with measurements of pulmonary func- tion and genoto?tic exposure. In addition, a small in- vestigation with volunteers exposed to dilute engine emission was carried out in which the same occupational hygiene, medical, and toxicologic measurements were used as at the workplaces. Workplaces, job descriptions and measurement srraregies Bus garage. In March--April a bus garage was investigated in which there were large and small dieselpowered vehicles and gasolice-driven buses used for transporting disabled persons. The work performed there, in addition to storage and engine warm-up, included refueling, washing and repairs. In the morning, afternoon, and evening elevated concentrations, in particular of diesel exhaust, accumulated in the garage bays when most buses left for or returned from assignments. The occupations represented were marshaler ( 2 workers), cleaner ( I worker), foreman (2 workers), 3 505 Table 1. Characterization of the workers (men only) exposed to mixed exhaust (gasoline and diesel fumes)or to primarily diesel exhaust in the workplaces chosen for the tnvestigation. Workplace Number of subjects Smokers Nonsmokers Total Age (years) Mean SD Height (cm) Mean SD -- Weight (kg) Mean so .Mixed e.rhausr Bus garage Car ferries Diesel exhaus1 Roll-on roll-off ships I II 5 12 17 15 10 25 12 1 1 23' 13 1 1 24= a Ten persons took part on both occasions at the ro-ro ships 32 10.3 36 11.4 34 7 0 36 6.3 180 7.6 177 5.7 180 70 181 ___7 0 80 9.2 76 10.5 a2 9 4 ai 1 1 o Table 2. Chemical characterization of the air samples. obtained with a personal Sampling technique. from the workplaces and from the experimental study and the occupational exposure limits of the substances determined. The readings from the ro-ro ships are averages for a whole workshift Other results represent the exposure measured for part of a day In the latter instances the measurements #ere carried out during the course of 'work entailing exposure Range of the substances determined - Bus garage Car ferry (2 h run) Car ferry (20-min run) Roll-on roll-off ships I II C Experimental study Occupational exposure limit9 Ceiling Shon4ime value Time-weighted average limit 028-15 < l o 049- 1 5 <lo 102-2 1 a30 <16 0 3 OM 90 30000 45 5000 ' Respirable dust Single measurement. Second study occasion. Taken from reference 27 a02 so2 a03 02 30 16 046' 01-03 004-08 17- 24 003-531 13-100 01-03 5-190 02-11 <06 02-08 03-10 006 02-10 <18 <18 < 190 013-059 a003 1 4 - 2 7 015-10 01-06 0002-002 03-10 01-05 11-51 006-23 002-07 06 005 53 3 9 56 12-14 <02 <02 <08 13 15 10 120 60 '5 40 4 30 13 400 5 300 i and mechanic (12 workers). Those responsible for driven on and off the car deck. Samples were only the workplace had rated the ventilation as not fully taken during the loading and unloading of vehicles. I satisfactory. Curferry. In June-July two types of car ferries were studied, one serving on a 2-h route and the other on a 'O-min route. The j o b of the upper deck crew on the former was to direct vehicles to and from their parking places on the car deck. Loading and unloading averaged 20 min. In the intervals between the loading and unloading, the deck crew performed other tasks. The first and second mates had duties on the bridge during crossings. On the second :ype of ferry, work consisted of directing vehicles to the right place as they came aboard (so the maximum number of cars and lorries could be accommodated on the car deck) and assisting in the unloading of vehicles from the deck after the ferry had docked. Their work also included mooring the ferry. The mate's j o b was to lower the gangway after docking, check the tickets of passengers traveling in vehicles, and supervise operations while vehicles were Roll-on roll-off ships. The investigations aboard the roll-on roll-off (ro-ro) ships were carried out in January-February and in June and covered lower deck crew whose exposure to exhaust gas was judged to be the heaviest. During loading, cargo was moved from the quay onto the ship with large diesel-powered trucks. Once the cargo was on deck, smaller trucks took over and carried out the final stowage. The work of each truck driver was directed by one or t w o men on the deck. A supervisor was in charge of one or more decks. The truck drivers drove their trucks aboard ship and also spent a short time on deck. Drivers of the big trucks transferred cargo between the quay and rhe ships. They remained in their cabs the ,.vhole workday. One group, made up in part of supervisors, placed padding, etc, under cargo to keep it steady. The supervisors directed the loading and unloading o i cargo. imenfs in fhe exposure chamber. Six workers placed in an exposure chamber (interior dimen- 4.9 x 2.9 x 2.5 m) into which exhaust gas, diluted ? r, from a diesel-powered vehicle was piped. The on was adjusted so that the nitrogen dioxide in I chamber amounted to about 2 ppm. .- he test vehicle was a 1980 Volvo 244D automobile +'with a manual, four-speed transmission. The vehicle 1 -&as powered by a six-cylinder, precombustion chamber 1 &"I %>.a d engine (2 383 cm'). The the engine output 60 kW. compression was 23: I , During the experiment dthe vehicle was run at a constant speed, equivalent to ~ 'PISO k/h in third gear. This rate produced an engine ' 'qxcd of about 2 580 revolutions/min. The engine load 'was calculated as 18 kW (maximum engine output ' about 35 kW at the indicated engine speed). This engine 1 . ;.,bad is about four to fibe times higher than the load daring driving on a dry, level road. The engine was ; . k p t running for 3 h and $0 min without interruption. . .. Hygienic measurements and chemical ana1.vsis .-Totaldust and respirable dust were collected on *., .Fllulose acetate filters in personal and stationary --- ,., S..ampling equipment. The sampling of formaldehyde . md acetaldehyde was performed with personal sam- :. f i g equipment with chemosorption, and the samples .I . ' - .'-~-.w%.egrreapahnyaly(z2e,d3 with ). H high-performance ydrocarbons were liquid chromacollected in an *inurn laminate bag and then analyzed with a non- Specific. direct-reading photoionization detector (HNU , PI 101). Some samples were taken with a carbon tube ' Tenax' tube and then analyzed with gas chroma- tography. Hydrocarbons were sampled with personal - equipment only. Both the personal and the stationary sampling was carried out for mass spectrometry determinations of h z o ( a ) p y r e n e and total polycyclic aromatic hydro- ' carbons (PAH). The particles were collected on glass fiber filters, whereas gas samples were collected by two- stage chilling o f the samples with water and dry ice and ethanol. The samples were analyzed with a mass ' spectrometer employing multiple ion detection ( 1 5 ) . Air was collected in an aluminum laminate bag and analyzed for carbon monoxide with a direct-reading instrument containing an electrochemical cell (Interscan 1134)and for nitric oxide and nitrogen dioxide with a direct-reading instrument (Monitor Labs 8440) according to the chemiluminescence principle. Sulfur dioxide was determined with a direct-reading instrument (Interscan) according to an electrochemical measuring principle. Nitrous acid and nitric acid were collected in glass tubes coated with sodium hydroxide. Subsequent analysis was carried out with ion-exchange chromatography (17). Acetone extracts of the particulate component of three air samples from the exposure chamber experiment were anaiyzed for mutagenicity in the Ames test with two bacterial strains (Salmonella lyphimurium, TA 98 and TA loo),both with and without metabolic activation ( I ) . Biological methods Determination of urinary muiagenicity and urinary ihioeiher excretion. Workers occupationally exposed to engine exhausts were asked to provide urine specimens (on a random basis) immediately before going to work (unexposed sample) and again at the end of or immediately after work (exposed sample). The urine specimens were immediately frozen and stored at - 20C for several months. The subjects in the experimental exposure supplied urine specimens before and at several times after the exposure (table 3). Since it has been found ( 5 ) that diet may have a powerful effect on the urinary excretion of thioechers and it can be assumed that certain drugs are capable of influencing thioether formation, dietary intake was standardized during the experimental day. In addition the subjects refrained from taking any medication. They carefully avoided certain vegetables (the cruciferae family such as cabbage and horseradish) which contain comparatively large amounts of thiocyanate ( 5 , 37). The urine specimens were immediately frozcn and stored at - 20C for several months. 1. 'We 3. Thioether concentralion and mutagenic activity in the urine o f six Norkers before anc after the expenmental exposure lo diesel exhaust gases [Si = stancard error of the mean) ~ ~ Thloetner concentrat ion lmoirmol ireatininel -_ M o r e exposure Aner exposure hours after exposure ,I '%ht hours after exposure _Next morning Mean 27 26 25 27 23 .- SE 04 03 03 03 02 SJ/mOnei/J iyph/murfurn TA 98 t s-9 mix ,revert ants mol c'eatinlner -S 9 mtx (revertants: mol creatinine) Mean SE Mean SE i 8 i a '06 ea 46 54 24 153 64 170 51 300 112 380 143 0 Escherfchia coli WP2 uvrA + s-9 mix (revertants/mol creatinine) Mean SE 780 56 33 19 85 18 8 96 :-'% f 2One sample exceeded 600 One sample exceeded 300 I i9 15 f'> i Two bacterial strains were used for the determina- Linear regression analyses were performed in intra- tion of urinary mutagenicity, S typhimurium T A 98 and interindividual comparisons between degree of and Escherichia coli WP2 uvrA. T h e analyses were exposure and lung-function effect. The tWO-tailed carried out at the Mutagen Laboratory o f the In- Student's t-test was used (30). stitute of Occupational Health, Helsinki, using the copolymer XAD-2 (for the determination of the con- czntrations in the urine specimens) and the fluctua- Results tion method (16, 38). The urinary concentrations of the thioethers (13) were determined by spectrophotometry. using Ellman's reagent after hydrolysis to thiols according to the method described by van Doorn et al (34, 35). AI1 the exposed persons (see table 1) were examined with the use of spirometry and the single-breath nitrogen-washout technique. The subjects from the car ferries and bus garage were examined on a Monday after a 2-d break from work. Stevedores on the ro-ro ships were examined after a IO-d break from work. All the exposed subjects were examined before they entered the work premises and after the workday. The exhaust concentrations in the air were determined with a personal sampling technique during the workday. On the basis of these results the study was expanded to include a second examination of the stevedores on the ro-ro ships on a later occasion. Prior to the examina!ion, the stevedores were not exposed to exhaust gases for 5 or 6 d . After exposure to emissions for I or 2 d, the group was monitored during unexposed work so as to determine the time needed for pulmonary function to recover after deterioration. Exposure conditions An overview o i the workplaces visited, the subjects, and the measured concentrations of substances can found in tables I and 2. The carbon monoxide peaks were lower in the bus garage (where diesel-powered vehicles were predominant) than on the ferries. The carbon monoxide con- centrations were also low on the To-ro ships on which only diesel trucks were used. The blood of exposed nonsmokers before and after a workshift displayed no increase in carboxyhemoglobin. The concentrations of nitrogen oxides were not higher than at the other workplaces where both gasoline- and diesel-powered vehicles were used. At the concentrations tested, none of the three extracts from the filter samples was toxic to either strain of S fyphimurium (TA98 o r T A IOO), but extracts were mutagenic and produced a linear dose-response relationship. The maximal number of observed revertants per cubic meter of air sample was 643 for strain TA 100-S9. ,Mutagenicity W ~ Sobserved both with and without a rat-liver metabolic system (S-9mix), but the response was slightly lower in both strains when Forced expired vital capacirv was recorded with metabolic activation was used. a low-resistance bellows spirometer (Ohio 740). At least two measurements were taken per person. The best result for each variable was chosen, even if the value had to be taken from different determinations. and the volumes were adjusted to conditions of body temperature and pressure saturated with water vapor (BTPS) (19). The following variables were determined: foried vital capacity (FVC), forced expiratory Lolume in 1 s (FEV, "). FEV% [(lo0 x FEV, ,,)/FVC], and maximal midexpiratory tlow (LIklF). Urinary muragenicily and urrnarv e.rcrerion of thioefhers 0ccuparionall.v exposed workers. Comparisons between the urinary mutagenicity of samples from an exposed and an unexposed period failed to disclose any significant differences between the number of revertants per mole of creatinine, ie, either in the occupationally exposed group as a whole or after the group had been divided into smokers and nonsmokers. A few samples displayed values that were barely above the Reference values for the spirometric variables were limirs regarded as mutagenic ( >600 for S [.vphirnurium taken from Berglund et al (9) and Birath et a1 ( I O ) . and > 300 for E coli) (16). All but one of these urine Single-breath nitrogen washout (4)was studied with specimens had been submitted by smokers. For the the use of rhe aforementioned bellows spirometer and mutagenicity of the S t.vphimuriutn strain T A 98, the a "bag-in-box" unit. The nitrogen concentration was mean value for the smokers was higher than that of measured with a n analyzer operating on the ioniza- the nonsmokers [mean 231 (SE 58) and 197 (SE 54) tion principle (Ohio 720).The gas concentration and rebertants mol of creatinine. respectively]. volume were documented on an N-y rzcorder (Bryans N o significant differences in thioether excretion were 26OOO). At least two measurements were taken at a n found betueen the samples from the exposed and unex- interval of ?-IO min. The closing volume (CV) was posed periods, ie, either in the occupationally exposed expressed as the percentage of expiratory vital capacity group as a whole or after the group had been divided (CVmo). The slope of the alceolar plateau (phase I l l ) into smokers and nonsmokers rS.8 (SE 0.5) and 5.5 was expressed as the percentage of nitrogen per liter (SE 0.5) mmol/mol, respectively]. If, on the other of exhaled gas. The nitrogen washout data obtained hand, all the samples from the smokers are compared in this manner were compared to reference values from 10 all the samples from the nonsmokers, the value of Buist & Ross ( 1 I , 12). the smokers is significantly higher than that of the 508 nonsmokers ( 7 . 2(SE 0.6) and 4.7 (SE 0.4) mmol/mol, respectively, P = 0.001.] Experimental exposure. Neither the thioether findings nor any of the values obtained in the tests for urinary mutagenicity were increased after the experimental exposure to the diesel exhaust-air mixture. (See table 3 . ) Pulmonary function studies For each person, a comparison was made with the reference material on a Monday before work and after a break from work lasting at least 2 d (table 4). The exposed group displayed an average reduction of 0.33 I in FVC (P < 0.001) and of 0.23 I in FEV,., (P < 0.005).There were no differences between the smokers and nonsmokers. There were no correspond- ing significant changes in the MMF, CV%, or phase 111 variables. As a further check for a possible correlation between exhaust exposure and pulmonary function, various linear regression analyses were used, but they failed to disclose any significant correlations. The pulmonary function of all the exposed subwas studied before and after a workday. The I,--dn exposure on this day was as follows: nitric oxide 0.6 mg/m', nitrogen dioxide 0.54 mg/m', carbon monoxide 1. I mg/m', and formaldehyde 0. I5 mg/m'. Significant impairment in pulmonary function was found (table 4). The FVC declined by an average of 0.15 I and the FEV,., by a corresponding value of 0. I I 1. No changes were found in the MMF, the CV%, or the alveolar plateau gradient (phase 111). There was no significant difference between the smokers and nonsmokers in pulmonary function on Monday before work. The presence of any correlation between the ex- posure to various investigated Components in ex- haust gas and the investigated pulmonary function variables was studied. However, no correlation was found between the changes in pulmonary function and exposure to nitric oxide, nitrogen dioxide, or formaldehyde in comparison with either peak values or the mean values for the various components in the exhaust gases during one workshift. Nor was any correlation found between the changes in pulmonary function and the carbon monoxide concentration. The group of stevedores who had only been exposed to diesel emissions on ro-ro ships had a 10-d break from exposure before the medical investigation. There was no difference between the values of this group and the reference values before the start of the workday (table 4). However, pulmonary function did display deterioration during a workshift. The deterioration averaged 0.44 1 for FVC and 0.30 I for FEV,.,. There was no difference between the smokers and non- smokers. A new study was carried our on another group of stevedores (N = 24) to ascertain whether the Table 4. Spirometric and nitrogen wash-out data for the exposed subjects (according to type of exposure) on a Monday before work and after periods of 2. 5. 10 and 13 days of no exposure and after 3 days of exposure Reference Values were matched Ni!h regard ! o sex. age and height (8. 10, 11) ( F V C = forced vital capacity, FEV,, = forced expiratory volume in 1 s. F E V % = (100x FEV, o)lFVC. M M F = maximal midexpiratory flow C V 0 6 = closing volume expressed as the percentage of expiratory vital capacity, Phase 111 = slope of !he aveolar plateau, N, = nitrogen) Number *e VI FVC (I) Mean SE F E V , o (1) Mean SE FEV% Mean SE M M F (Us) Mean SE cv % Mean SE Phase I l l ( O hNdl) Mean SE All exhaust exposure Reference value . 5.66 0.06 r P<O.OOOl I Monday before work 65 5.32 0 1 1 Mixed exnaust exposure 42 Reference value After 2 Q of no exposure Change during a shift 5.62 0.07 5.17" 0 1 4 + 0.01 Diesel exhaust exposure Reference value Aitw 1Od of no exposurea Change during a Shift after 10 d of no exposure Change during a shift after 5 d of no exposureD Change from the values "Qasured after !he shift ,wing 5 d of no ,osure after 3 a of recovery (no exposure) 23 24 . 5.72 0.18 5.62 0 16 - 044' - 016' +0.24" . 4.47 0.06 ? P=OOO5 I 4.24 010 4.44 4.10' 0.00 0.08 0.l1 4.53 4.50 0.10 0.17 - 030" + 0 02 +0.13 . 78.8 0.4 t P=0.005 I 79.7 0.9 78.7 0.06 8 0 7 0.18 -0.1 79.13 0.6 79.8 1.4 -10 + 2 5' -0.8' 4.32 0.06 4.42 0.16 4.29 0.08 4.30 0.18 - 0.10 . 4.38 0.00 4.65 0.30 - 033 +023 +0.04 . 12.2 0.5 12.9 0.8 11.8 0.8 12.5 1.1 +0.7 . 12.2 13.2 0 10 000 0.7 1.3 0.00 . 1.04 0.01 1.13 0.07 1.02 0.02 1.00 0.08 -0.12 . 1.04 0.02 1.27 1.22 + o 12 000 0.00 . a Sludy occasion 1. Study occasion 2 (10 of these subjects took part in both investigations) P s 0 . 0 1 . " Ps0.001 (Student's two-sided t-test). 509 1 4 u 4 7 1 E': ti - I- s:? -& "acute" deterioration in pulmonary function found in the stevedores during one workshift was reproducible and, if so, how long any normalization would take. On this occasion exposure conditions were about the same as in the first investigation series (table 2 ) . In this case, the break in cxposure prior to the investigation was 5 to 6 d. As in the first investigation, no significantly impaired pulmonary function was found before the workshift. But acute deterioration was recorded for FVC (which averaged 0.16 I) during one workday. This decline was accompanied by an increase in FEVWo. As table 4 shows, this decline in pulmonary function normalized after a 3-d break from exposure. Ferry and garage personnel exposed to both gasoline and diesel exhaust had a 2-d break from exposure before the measurement of pulmonary function began before work on Monday. A decline in pulmonary function was found in this group (0.151 for FVC and 0.34 I for FEV,,,) in comparison to the reference values (table 3). No additional deterioration was found in the pulmonary function during a workshift. Discussion Exposure conditions In the experimental study the nitrogen oxide concentrations were generally higher than any peak con- centration found at the workplaces at which only diesel engines were used (table 2). The concentrations of carbon monoxide were comparable with the peak concentrations found at the workplaces using diesel engines. The total concentration of particulate-bound and gaseous PAH was 638 ng/' in the exposure chamber. The low molecular-weight compounds (methyl phenanthrenes, anthracenes, and phenanthrene) accounted for 7'6 "0 of the total P.AH content. Grnoroxicity The particulate extract of the air samples from the exposure chamber displayed clear genotoxicity with a linear dose-response in the Ames test. Both test strains used, ie, S iyphrmurium T A 98 and T A 100, yielded a higher response when no exogenous metabolic system was used. This finding points to the presence of direct-acting mutagenic substances [eg, nitroarenes such as I-nitropyrene (28, 29)) characteristically found in diesel exhaust. The ambient air samples taken from the exposure chamber during the voluntary exposure experiment and several previous studies performed on engine ex- haust have all shown these emissions to be mutagenic, irrespective of the fuel type (14, 15, 22, 13,26, 28, 29). However no mutagens were found in the urine specimens of our subjects occupationally or experimentally exposed to vehicle emissions. The negative results of the mutagenicity analysis of the urine d o not preclude the absorption of mutagenic substances from engine exhaust. Several earlig (31. 38) have shown the test strain S fyphimu",,,,, TA 98, with metabolic activation (s-9mix) to besensitive to tobacco smoke. The smokers in the p r w study also displayed greater mutagenic activity thPll . the nonsmokers. The excretion of thioethers in urine was sj,,,,b . before and after exposure to engine exhaust. the other hand, the values of the smokers were ~ i ~ - nificantly higher (P = 0.001) than those of the mIC smokers. This finding agrees with results r e p o d earlier ( 5 , 33). The individual results for the mpa- tionally exposed subjects (some values exceeding 10rnmol/mol of creatinine in samples taken beforen, posure but declining in those taken Jter exposure) in- dicate that factors unrelated to the work environment, ie, probably dietary factors ( 5 , 37) or possibly medica- tion, had affected the results obtained for certain individuals in this group. The lower thioether levels a d . the lower variation in the values obtained in the ex- , perimental study, compared to the values of the 0 ~ - cupationally exposed persons, might be due to the diet standardization smployed in the experimental study. The negative results of the urinary assays do not preclude the possibility that exhaust exposures may cause local mutagenic effects in, eg, lungs and airways, the regional lymph system, or the gastrointestinal tract, after exhaust particles are swallowed. Compounds a- creted in bile were not detectable with the urinary assay methods used. Respirafory effects Exposure to exhaust fumes appeared to impair puimonary function. These effects were found on a Monday morning, before work began, after cessation of exposure for at least 2 d and were accentuated during a workday with exposure to exhaust fumes. The subjects comprised stevedores exposed only to exhaust from diesel-powered trucks and ferry and garage personnel exposed to both diesel and gasoline exhaust fumes. The stevedores had had a 10-d break from exposure before the investigation started and displayed normal pulmonary function on the ,Monday before going to work as compared with the reference material. However, both their FVC and FEV,,, values deteriorated during a workday with exposure to exhaust. Similar but less pronounced effects were found in a second, subsequent study. Pulmonary function returned to normal after 3 d without occupational exposure to exhaust fumes. The recovery to normal function after three exposure-free days may explain why the stevedore group did not display poorer pulmonary function than the reference group before exposure. This finding is consistent with the fact that no chronic lung effects solely attributable to exhaust gases and particles have been discernible in various cross-sectional studies of persons exposed to diesel exhaust ( 6 , 7 , 8, 18, 24). ~ . . , 510 After a 2-d break in exposure, the ferry and garage personnel exposed to mixed exhausts displayed a deterioration in pulmonary function of the same nature and magnitude as the stevedores after work. The functional deterioration showed no progression after one workday. Thus the same degree of dysfunction was observed in both the stevedores exposed solely to diesel exhaust and in the ferry and garage workers exposed to mixed exhaust emissions. These findings suggest that subjects w h o display functional deterioration after previous exposure to exhaust gases may not display any additional deterioration after renewed acute exposure and that subjects who have time to recover during a break from exposure may display acute deterioration. However, the interpretation of these findings is complicated by the differences in the exposure of the stevedores and thar of the exposure of ferry and garage personnel and by the fact that no dose-related correla- tion was found between any irritating substances in the exhaust gases (nitric oxide, nitrogen dioxide, and formaldehyde) and an effect on pulmonary function. Nor was any correlation found with the carbonmonoxide exposure, investigated as a possible indicator of exposure to all exhaust compounds. decline of up to 0.4 I in the FVC during a work- \ orresponded to a deviation of less than IO To from prework values. Smaller differences were found for the other variables. Presumably, these changes d o not produce any discernible impairment in physical work capacity during moderate physical exertion, but they are a ciisturbing finding in a cross-sectional study since their prognostic implications are unknown. The occupational exhaust exposure levels measured are among the highest in Sweden, and they appear to affect pulmonary function during a workday but cause relatively few subjective symptoms. This decline, which is reproducible in repeated measurements, normalizes after a few days without exposure to exhaust emissions. The changes are relatively slight and need not have any significant effect on physical work capacity. Because the changes are small, the nature of the dysfunction is difficult to assess. The decrease in FVC and FEV, o, but not in FEY'% or M41F.like the virtually normal. single-breath nitrogen washout findings. may sueg,oes[ a restrictive rather than an obstructive dysfunction, or a combination of borh. Possible indicarors of exhaus! exposure !II group itudie,. formaldehyde at concentrations of 0.40 m g ' m ' in the air has been shown to be capable of affecting pulmonary function, ie, causing main11 obstruction. Formaldehyde alone, at concentrations down 10 0.05 ppm (0.06 mg/'m'). irritates the nose, e' and throat of sensitive people and produces di- .nlort at somewhat lower concentrations ( 2 5 . 39). I t is possible that aldehydes could explain some of the airway symptoms found in the present study. The lebels were relati\ely 10%. and a higher iricidence of eye. nose, and rhroat symptoms might have been expected. High concentrations of nitrogen dioxide are known to cause acute effects on the lungs (20). Nitrogen dioxide produced increased respiratory resistance after a 15-min exposure in the 1.6-2.0 ppm (3.6- 2 9 mg/m') concentration range. Lower concentrations produce nasal irritation and laryngitic symptoms but no changes in lung physiology (21). I t should be pointed out that the alveolar concentration of several of the gases may be even higher than concentrations in the breathing zone, since additional input of injurious agents could conceivably occur by adsorption onto the soot particles present in exhaust emissions. The particulate phase in diesel exhaust resembles carbon black, since the particulate matter consists of more than 85 mo elementary carbon in the form of nearly spherical particles formed in the partial combustion of hydrocarbons. Diesel particles and carbon black particles are almost always respirable (36). A calculation assuming adsorption of a monomolecular layer of nitrogen dioxide on a diesel aerosol indicates that the surface area of aerosol particles is sufficient to permit the particle-bonded nitrogen dioxide to constitute a substantial proportion of the total nitrogen dioxide concentration. In summary published data on the effects of the substances studied at different concentrations and on measured concentrations of these substances in occupational exhaust exposure d o not rule out the possibility that nitrogen dioxide and formaldehyde, or both, may give rise to effects on lung and mucous membranes at the concentrations found in practice. Acknowledgrnen ts The project received financial support from special project fund5 held by the National Board of Occupational Safety and Health. References I . .Arnes BN. XlcCann J . Yamasaki E. Methods for detecting carcinogens and mutagens with the Su/inone//u/ mammalian microsome teSt. Xlutar Res 31 (1975) 347. 2 . l n d e r t s o n K . Hallgrrn C. Lrvin J - 0 , Nilsson C-A. Solid chrmo\orbenr ior sampling tub-ppm levels of actrolein and gluiaraldehyde in air. Chemosphere IO 11981): 3, 275-280. 3. .\ndersson K, Hallgren C, Levin J - 0 . Nilsson C-A. Chemosorption sampling and analysis of formaldehyde in air. Scand J R'ork Environ Health 7(1981)282--289. 4. 4ntonitrn NR. Report o f international session on "closin_evolume" determinations. National Heart Lung Institute. Bethesda. \ l D 1972. 5 . \ringer L. Hogstedt C, Lidums V . Svensson E, Wrange R . E\aluation of some factorr affecting determination of thioerherr in urine. In: Institute of Occupational Health. International seminar on methods of monitoring human exposure to carcinogenic and mutagenic agents. 12-13 Dec 1983. Helsinki 1983. p 37. (Abstract). 6. Artfield V D .The effect o f exposure of silica and diesel ethaust in underground metal and nonmetal miners. In: .American Conference of Governmental Industrial Hygienists. ACGlH conference on mining and tunneling. 511 Denver. CO 1978. pp 129-135. 7. Attfield MD, Trabant GD, Wheeler RW. Exposure to diesel fumes and dust at six potash mines. National Institute for Occupational Safety and Health, Morgantown, WV. and MSHA, Denver, CO 1980. pp 1-19, 8. Battigelli %IC.Mannella RJ, Hatch TF. Environmental and clinical investigation of workmen exposed 10 diesel exhaust in railroad engine houses. Ind Med Surg 33 (1964) 1'1-124. 9. Berglund E. Birath G. Bjure J, Grimby G.Kjellmer I. Sandqvist L. Soderholm B. Spirometric studies in normal subjects. Acta .Med Scand 173 (1963) 185-189. IO. Birath G, Kjellmer J, Sandqvist L. Spirometric studies in normal subjects: I1 Ventilatory capacity tats in adults. Acta .Wed Scand 183 (1963) 193-198. 1 1 . Buist AS, Ross BB. Predicted values for closing volumes using a modified single breath nitrogen test. Am Rev Respir Dis 107 (1973) 744-752. I?. Buist .AS, Ross BB. Quantitative analysis of the alveolar plateau in the diagnosis of early airway obstrucrion. Xm dinger R, Tejada S. Bumgarner J, Duffield F,Watm Simmon VF. Hare C. Rodriquez C,Snow L. Appijation of bioassay to the characterization of die%[ m i d e emissions. In: Waters MD, Nesnow S, Huisingh JL Sandhu SS, Claxton L. ed. Application of s h o n - t d bioassays in the 20-fractionation and analysis of corn. plex environmental mixtures. Plenum Press, New York, NY 1978. pp 383-418. 24. Jorgensen H, Swensson .A. Studies on pulmonary func. [ion and respiratory tract symptoms of workers in iron-mine ore where diesel trucks are used underground: .IOccup Med 12 (1979) 338-354. 25. Kolmodin-Hedman B. Nordman H. Formaldehyde. Nordic Expert Group for Documentation of hpa- tional Exposure Limits :In Swedish]. Arbetarskydb. verket, Stockholm 1982. (Arbete och halsa 1982: 27). (English abstract). 26. Liwtas J . Evaluation of the mutagenicity and car- cinogenicity of motor vehicle emissions using shon-tm, bioassays. Environ Health Perspect 47 (1983) 141-152. Rev Respir Dis 108 (1973) 1078-1087. 27. National Board of Occupational Safety and Health. 13. Chasseaud LF. The role of glutathione and glutathione- Hygienic limit values. Stockholm 1984. (AFS 1984:5 ) . S-transferase in the metabolism of chemical carcinogenic 28. Rannug U. Data from short-rerm tests on motor vehicle i and other electrophilic agents. In: Klein Y. Weinhouse exhausts. Environ Health Perspect 47 (1983) 161-170. S, cd. Advance in cancer research. Academic Press, New 29. Rosenkranz HS. Mutagenic and carcinogenicnitroarena York, N Y 1979. pp 175-255. 14. Egeback K-E, Xhlsberg T, Westerholm R, Rannug U, ? Winqvist L. Exposure chamber experiment with diesel exhausts: Generation of exhausts, concentrations of E polyaromatic hydrocarbons and mutagenicity in air samples [In Swedish). Technical unit, Research Depan- 5 ment. Swedish National Board of Occupational Safety in diesel emissions: Risk idcntificarion. Mutat Res 140 (1984) 1-6. 30. Snedcor GW, Coltrow WG. Statistical methods. 6th Iowa State University Press, Ames, I A 1967. 3 1. Sorsa IM, Falck K. Heinonen T, Vainio H, Norppa H, Rimpela M. Detection of exposure to mutagenic compounds in low-tar and medium-tar cigarette smokers. and Health, Solna 1984. Environ Res 33 (1984) 312-321. 15. Egeback K-E, Telje G, Stenberg U,Westerholm R. Als- 32. Ulfvarson U, Alexandersson R. Aringer L, Ansheim. berg T, Rannug U. Sundvzll A. A comparative study of diluted 3nd undiluted automobile exhaust utilizing Olson B, Einisto P, Ekholm U , Hedenstierna G , Hogstedt C, Holmberg B, Lindstedt G. Randma E. Roen polynuclear aromatic hydrocarbons analysis and mutagenicity tests. Central Institute for Industrial Research, Oslo 1981, pp 1-25. (Nordic PAH project repon no 13). 16. Falck K. Application of the bacterial urinary muta- geniciry assav in detection of exposure to genotoxic chemicals. Institute of Occupational Health, Helsinki 1982. (Doctoral dissertation). G, Sorsa M,Svensson E. Halsoeffekter vid exponering fdr motoravgaser [Health effectsof exposure to motor exhaust gases]. Arbetarskyddsverket. Stockholm 1985. (Arbete och halsa 1985: 5). (English summary). 33. Van Doom R. Bos RP. Lcijdekkers C-tM, WagenaasZegers MAP. Theuws JLG, Henderson PT. Thioether concentration and mutagenicity of urine from cigarette smokers. Int .Arch Occup Environ Health 43 (1979) 17. Ferm M ,Sjodin .A. h slmple method for determining 159-166. of gaseous nitrous acid in the atmosphere. Swedish 34. Van Doorn R, Leijdekker C-M, Bos RP, Brouns Environmental Research Institute. Goteborg 1983. R.ME. Henderson PT. Detection of human exposure to (Pub1 no B -18). electrophilic :ompounds by assav of thioerher detoxica- 18. Gamble 1. Jones W. Hudak J. .An epidemiological study of salt miners in diesel and non diesel miners. Am J Ind Med 4 (1983) 435-458. 19. Gardner Rk1. ATS statement-snowbird workshop on standardization o f spirometry. Am Rev Respir Dis 119 (1979) 31-38. 20. Green FHY, Boyd RL. Danner-Rabovsky J, Fisher .MJ, Moorman W J , Ong TM, Tucker J , Vallyathan V, Whong W-Z,Zoldak J. Lewis T. Inhalation studies of diesel exhaust and coal dust in rats. Scand J Work Environ Health 9 (1983) 181--188. 21. Grenquist-Norden 8 . Nordiska expertgruppen f6r ~ransvardesdokumentation:45. Nitrosa gases [Nordic tion products in urine. Ann Occup Hyg 24 (1981)77-92. 35. Van Doorn R. Leijdekker C-M, Bos RP, Brouns R,ME, Henderson PT. Enchanged excretion of thioeters in urine o f operators of chemical waste incinerators. Br J Ind Med 38 (1981) 187-190. 36. Willeke K, ed. Generation of aerosols and facilities for exposure experiments. .Ann Arbor Science Publications Inc. Ann Arbor, M I 1980, pp 1-597. 37. Wood JL. Biochemistry: Plants. In: Newman .LA,ed. Chemistry and biochemistry of thiocyanic acid and its derivatives. .Academic Press, London 1975. pp 157-162. 38. Yamasaki E, Ames BN. Concentration of mutagens from urine by adsorption 'with the non-polar resin E,xpsrt Group for [he Documentation of Occupational XhD-2: Cigarette smokers have mutagenic urine. Proc Exposure Limits: 45.Yitrosen oxides]. Arbetarskydds- Narl ,\cad Sci USA 74 (19771 3555-3559. 'jI verket, Srockholm 1Y83. (Arbste och halsa 1983: 28). 39. -. Report on the sonsensus workshop on form- (English abstract). aldehyde. Environ Health Perspect 58 (1984) 323-380. 22. Holmberg B. Ahlborg U. Consensus report: .Muta- genicity and carcinogenicity of car exhaust and coal com- bustion emissions. Environ Health Perspect 47 (1983) 1-28, 23. Huisingh JL, Bradow R, Jungers R, Claxton L, Zwei- Received for publicarion: 2 January 1986 i 512 JOM Volume 35, Number 2, February 1993 149 Diesel Asthma Reactive Airways Disease following Overexposure to Locomotive Exhaust John F. Wade 111, MD Lee S. Newman, MD Diesel-powered equipment has long been used in industrial applications. resulting in diesel exhausr exposure for nilroad workers. miners. bridge and tunnel workers. truck driven a i d While some of the gaseous and paniculate components of diesel txhaust bus maintenance garage workers. can cause pulmonary irritation and bronchial hyperreactivity,diesel eyhaust among others. The Yational Institute e-rpostire has not been shown to cause asthma Titree railroad workers for Occupational Safety and Hedth developed asthmafodowing excessive exposureto locomotive emissions while (NIOSH)mimated in 1983 that be- riding immediately behind the lead engines of caboose-less trains. Asthma meen l and 1.5 million workers were diagnosis was based on symptoms. pulmonaryfunction tests. and measure- exposed to diesel emissions.' LMount- ment of airways hyperreactiviry to methacholine or aercise- One individual's ing concerns about potential health peak txpiratoryflow ratesfill in a work-related pattern when riding immediately behind the lead diesel engine. .Vane had a previous history of asrhma or other respiratory disease and none were current smokers. All three developed persistent asthma. In two cases. phvsioiogic abnonndities suggesting reversibleresrricrion were observed. Thir is thefirst report implicating diesel exhaust as a cause of reactive ainvays disease. etfects of diesel exhaust have led to numerous studies of the carcinogenicity and respirator), consequences of chronic exposure.'-" Much less is known about the acute respiktory cf- f a of hi& level exposure to diesel exha~sr.'','~ We have identified three railroad workers who deveioped new asthma h r n diesel cxhausr inhalation. Over- exposure to diesel combustion prod- ucts occurred in these individuals after two railroad companies had dis- continued the use of cabooses on &eight trains. One of the principie functions of the caboose is to shuttle sccond railroad crews for future runs, a practice called "deadheading." As a result of c3boose-less trains. desdheding crews have to ride in loco- motive units trailing immediately behind the lead locomotive. In each of our patients, diesel exhaust from the lead unit entered the second unit, inducing acute or subacute onset of asthma. From the Puimonav Division and Occupauonal/Environmental ,Medicine Division. Na- tional Jewish Center for Immunology and Respiratory Medicine (DrNewman), and Division of Pulmonary Sciences. Depanment of Medicine (DnWade and Newman) and Dqxmment of Rcvenuve Medicine and Biometrics, University of Colorado School of Medicine (Dr Newman), Denver. Colo. Address correspondence to: Dr Newman. National Jewish Center for lmrnunology and Rapintory Medicine. l j o o JacksonS t m Room DIM,Denver, CO 50106. 0096-1736/93/35024l49303.00/0 Copyright 5 by ,AmericanCl~llegeof Occupational and Envimnmcntal Medicine Report of Cases case 1 A 40-yex-oldwhite man developed pmistent dyspnea beginning acutely during a 5-hour exposure to diesel locomotive exhaust in Apnl 1987. 150 DieselAsthma Wade & Newma.n - The patient. employed for 14 years as a railroad conductor and brakeman. had been riding in the sccond locomotive unit trailing immediately be- hind the lead locomotive. The lead engine's diesel exhaust blew airnost continually into the cab in which the patient was riding, producing acute symptoms of shortness of breath, burning chest pain with inspiration. and burning eyes. The patient reported no cough. fever, or hemoptysis and had no intercurrent respiratory infmion at the time of exposure. He had no prior hisrory of ashma allergies. bronchitis, pneumonia or other respiratory illness. He was a former smoker ( 17 pack-yean) having quit in 1982. The patient reponed that he had never experienced work-related respi- ratory symptoms or previously been overexposed to diesel exhaust until then, noting that deadhead crews did not ride in the second unit of cabooseless trains until approximately 6 months before the onset of hs symp- toms. He noted that wind direction had contributed to the intensity of hs acute exposun. Upon arrival at the train's destina- tion. the patient was seen at a local emergency room where he was found to be dyspneic, with poor air movement and conjunctival injection. Spi- rornevy was not performed. but arterial blood gas analysis demonstrated profound hypoxemia (Po235m m Hg, O7saturation 69%. pC0234 mm Hg. pH 7.45). He was treated as an inpatient with coniconeroids and supplemental oxygen, leading to gradual improvement in symptoms and oxygcnation. Because of penistent dyspnea. the patient saw a pulmonologist 3 weeks later, Reacrive aimys dixase was diagnosed based on the demon- stration of airflow limitation and ex- ercise-induced bronchospasm. Theophylline and inhaled beta-agonists produced subjective improvement, and the patient returned to work. De- spite medication, a second, similar exposure to excessive diesel locomotive exhaust 2 months later precipitated another severe asthma attack. Since that time. the patient's respiratory symptoms have been precipitated by nonspecific triggers such as exercise, cold air, and fumes. . - Fourteen months following the ini- tial accidenL the patient was refemd to the National Jewish Center for Immunology and Respintory Medicine. He had continued to experience episodic aggravation of his respiratop symptoms, although they were fairl! well controlled with oral theophylline. an inhaled beta-agonist, and inhaled triamcinolone. P s medical and occupational hinory was noncontributory, except as noted above.. The patient's father and brother had reacfive airways diseue. and his two sons had seasonal rhinitis. He had no allerges or atopy. P h y s i d examination revealed scat- tered expiratory wheezes and sli&: prolongation of expiratory phase on forced expiration. Chest radiograph was normal, as were radiographs from 1987 and 1988. Pulmonary function tests suggested a mixed restricfive and obstructive disorder. with improvement in airflow limitation following bronchodilator. Diffusing capaci::. was normai (see Table 1). Pulmonar. mechanics showed the patient to have nonnal elastic moil, suggesting th3t the mildly decreased lung volumes were related to the patient's weight rather than to coexisting interstit:zi lung disease. TABLE 1 Pulmonary Function Tests in Diesel Asthma Cases' ha81 Case 2 FEV, WC F E V i I N C (Yo) prat PO* P?O 2.57 (59) 3.81 (91) 3.31 (61) 4.75 (85) 78 .. 80 1.33 (38) 2.17 (45) 61 PO* 2.54 (73) 3.86 (80) 66 care3 Initial Follow-up Pm 3.16 (79) 3.55 (66) 89 Post 3.23 (81) 3.62 (67) 89 Pm Post 2.65 (65) 3.19 (81) 3.69 (69) 3.73 (70) 71 85 Total lung capauty 4.87 (67) 6.56 (90) 6.86 (107) 6.61 (103) 6.03 (86) 5.47 (78) 5.39 (T7) 5.27(75'1 Thoracic gas volume 2.92 (72) 3.49 (86) 3.98 (109) 3.80 (103) 210 (53) 2.05 (52) 2.62 (66) 2.31 (58) Residual volume 1.78 (84) 2.08 (98) 2.81 (135) 2.47 (118) 1.54 (95) 1.24 (76) 1.65 (99) 1.17 (75) DLccI1 106 Airways hypereactivity Positive+ 104 0.2 rng/dL" 157 6.2 mg/dL" 143 * Expressed in liters, with percent predicted in parentheses. unless otherwise indicated. t Measured prior to administration of inhaled bronchodilator. $ Measured after administratlonof inhale@bronchodilator. 5 Follow-up 3 years after initial exposure. 1 year after inrtial tests. IJ Single breathdiftusing capaaty for carbon monoxide (YO predicted). # Positive exeraseinduced bromhospaWn study. Provocative concentration of methacholine produang 200'0 oc greater drop in F N I (PC,FEVJ (nomalr 8 mg/dL). Note.-FEV,. forced expiratory volume in 1 second: N C .forced vital capaaty; O b . difh~singlung Capaaty forarbon mJnoxide. JOM Volume 35, Number 2, February 1993 15 1 Case 2 A SO-yur-old white man nonsmoker hadbeen in good h d t h , without prior history of lung disease or lower respiratory traa symptoms unul one evening in January 1987. The patient. employed Y a milroad conductor and brakeman for 25 yean. was riding in a diesel exhaust-filled second locomotive unit for several hours when he noted the acute onset of shortness of breath. dry cough. chest tightness and wheezing. Although he closed the windows of the cab, dim1 exhaust emanating fiom the lead locomotive entered through the scams in the doors and through the electrical panels, filling the cab with the most intense exposure he had ever experienced. He recalled previous more moderate diesel exhaust exposures. begmning when hls employer had removed the cabooses from the trains s e v e d months earlier. When the train's run was completed. he was admitted to a local hospital. He was found to have bilateral rhonch and hypoxemia ( ~ O5Z3 mm H& p C 0 ~31 mm Hg, pH 7.49). The patient improved with theophyl- line, inhaled beta-agonists and com- costeroids. but subjectively never returned to his preJanuary 1987 baseline. Upon returning to work he repeatedly experienced aggravation of his symptoms when exposed to diesel exhaust. even on shoner trips of less intense diesel exhaust exposure, Y il- lustrated by his peak expiratory flow mcs (see Fig. I). He gradually re- quired a more intensive medical regimen. including two courses of systemic conicosteroids. Two years after the original incid e n t the patient was referred to National Jewish Center for evaluation of persistent respiratory symptoms. He continued to have episodic aggravation of respiratory symptoms, despite oral theophylline. inhaled and oral beta-agonists, becfornethasone nasal spray. oral antihistamines. and a recent course of oral conicosteroids. Nonspecific triggers included cooking smoke. cigarette smoke. 3nd exenion. Past m e d i d history was notable for preexisting seasonal rhinitis con- trolled with antihistamines and prior nasal polypsomy. He had no history .ofaspirin sensitivity. previous asthma, or other lung disese. Family, occu- pational, and environmental histories were noncontributory except as noted ' 1 ' 2 l 3 ' 4 l 5 ' 6 ' f 1 8 I 9 l 10 DAYS Fq. 1. Recording of peak expiratory flow rates in case 1. performed in January 1990.2 years after initial onset of s t h m a Bars indiuu dl workshifts. Note the fall in pmk flow occurring shonly after the start of three shifts in which he rode in the train's second unit (solid bars).The patient's p k flows did not drop during one work wnod in which he rode in the train's caboose (hatched bar). above. Medical records indicated periphem1eosinophilia nnging from 6% to lj%,present since 1987. Physical examination revealed a Cushingoid male in moderate respiratory distress. He had diffuse, wheezing snd boggy, erythematous nasal mucosa without polyps. White cell count was 5.3 x 10y/Lwith 9% eosinophils. Serum immunoglobulin E was normal. Chest radiograph demonstrated hyperintlation and peribronchial thickening, the latter finding' having been present at the time of initial presentation. Pulmonary function tests showed airtlow limitation with significant improvement following bronchodilator and nonspecific ainvays hyperresponsiveness. Diffus- ing capacity was noma1 (seeTable 1). Case 3 A U-year-old Hispanic man neversmoker developed the subacute onset of episodic dyspnea on exenion, cough. wheezing, and nasal congestion beginning in late 1986. He reported a temporal association of these symptoms with high diesel exhaust exposures. usually within the first few hours of exposure. The patient. employed by the nilroad for 23 ye3rs. worked for the past 1 1 years as 3 brakeman. He had never experienced respintory problems until he k,3n riding in second locomotive units on deadhead runs where he described being exposed to significantly more diesel exhaust than in previous yean. The patient sought medical attention in early I987 because of increased frequencyof these episodic respiratory symptoms. A graded treadmill test produced bronchospasm and cough. Despite treatment with inhaled betaagonists. triamcinolone, several courses of oral conicosteroids. and removal from exposure. he remained symptomatic. Two years after symptom onset. he was referred to Yational Jewish Center with persistent. slowly progressive respiratory symptoms. P s t medical histor), was notable for von Willebrand's disew, rhinoplasty for a nasal bone deformity, and cholecystectomy. He had no allergies or atopy. Except for diesel exhaust. he recalled no significant past occupa- . 152 Diesel Asthma Wade & Newman - tional or environmental exposures. Physical examination r e v d e d a moderately obese male. The mucosa of the anterior nares was mildly hyperemic. Oropharynx was normal. Lungs were clear without wheezes. d e s or rhonchi. Chest radiograph was normal. Initial pulmonary tinction tests suggested a possible restrictive process without airflow obstruction. Diffusing capacity was elevated (Table 1). Pulmonary mechanics revealed normal elastic recoil of the lungs suggesting that his reduced lung volumes were probably due to obesity. We observed mild airways hyperreactivity to methacholine (Table 1). A gaded exercise treadmill test induced bronchospasm and cough. as had occurred in 1987. Accurate posr-exexise spirometry was not obtainable due to severe cough. On a follow-up visit 3 years after onset of symptoms. he remained symptomatic, noting nonspecific triggers such as grasses and exercise in cold or hot weather. Repeat pulmonary function tests showed airflow limitation with a sigmfiant bronchodilator response (Table 1). Comments Although millions of Americans are occupationally or environmentally exposed to diesel exhaus%' this is the fint time that diesel exhaust has been reponed as a cause of asthma. Several lines of evidence support the conclusion that railroad locomotive diesel exhaust exposure induced asthma in these three individuals (see Tables 1 and 7): 1) ail three demonstrated airways hyperreac~ivity,air flow limitation. and revenibiliry with bronchodilators. consistent with asthma: 2) none had preexisting asthma or Significant respiratory tract disea~e, based on our review of all past medical records and medical history; 3) each developed symptoms within the first hours of the overexposure to diesel exhaust: 3) in two cases. a single unusually high exposure led to immedi- ate firstime hospitalization and treat- ment for asthma: 5 ) all three experienced exacerbation of symptoms upon reexposure to locomotive diesel exhaust: and 6 ) in one individual. a work-related pattern of aidow limitation was documented by peak expiratory flow rate records. These three workers were employed by two different railroads and were unaware of the othen or of their shared diagnosis and etiology at the time of presentation. Asthma resulting from overexposure to diesel exhaust may occur more frcquently than is recognized. Kahn and co-worken recently reponed 13 cases of acute overexposure to diesel exhaust among railroad workers, two of whom complained of chest tight- ness and wheezing." The symptoms TABLE 2 Demographics and Clinical Features-of Disease in Diesel Asthma Cases case 1 Case 2 Case 3 Age (ye-) Smoking history Pior respiratorytract disease 40 Former None Pattern of disease onset Chest radrograph Acute Normal Subsequent nonspeafic rnggers' Ainvays hyperreactivitytestingt Airflow limitanon and bronchodila- tor response$ Peak expiratory flow records Duration of symptoms since onset (months) + + + Not done 14 50 Never Seasonal minitis. nasal polyps Acute Hypennflatlon, penbronchial mic)cening + + + 44 Never None Subacute Normal + + + Work-telated pattern 24 Not done 36 * Devdopment of asmrna symptoms resulting from nonspecific exposures, since time of diesel exposure. t By exeruse or methadoline challenge testing (seeTable 1). $ Based on FEV, p r e and post-albuterol(see Table 1). were suggestive of asthma however. no other clinical or physiologic data were provided in that report. %le a number of populationbased studies have examined the respiratory effects of diesel exhaust. none has tested for the development of asthma. However, data from s e v e d of these studies suggest that asthrn3 could be occurring. In a large study of diesel bus gaxage workers. Gamble and co-workers found a significant increase in eye irritation. labored breathing, chest tightness. and wheezing in a su&group of "high-exposure" individuals although these symptoms were not associated with puimonar; function decrements at any measured level of nitrogen dioxide or diesel exhaust paniculate concentration.'" These same investigators showed that bus garage workers with longer job tenure had a higher prevalence of dyspnea. wheezing, cough ana phlegm. and accelerated decline in spirometry compared to nonexposed control subjects." In another stud). dieselexposed salt miners expenenced a small but significant drop in FEV, across the workshift. correlating with increasing nitrogen dioxide le-;e1s.l' In a later study of salt miners. this same group found that phlegm production was associated with increasing diesel exhaust exposure. but cough. dyspnea, and pulmonary func- tion were not significantly different between the exposed and unexposed subjects." In contrast, other researcheK have found no effect of diesel exposure on respiratory symptoms or spirometry.-*i0." Many of the crosssectional studies may be biased by 3 healthy-worker effect with sthmatics less likely to stay in the work forc:. Taken in composite. these epidemiologc studies present contradictory results. probably due in part to the he:erogeneity of diesel exhaust." vanability in exposure conditions" and population and methodologc differences. None has anempted to rneasurt outcome variables pertinent to the recognition of asthma. such as airwa?s hyperreactivity or reversibility of airflow limitation. We do not know the levels of csposure to combustion products tha.! produced disease in our patients. as IS .. JOM Volume 35, Number 2, February 1993 153 commonly the c u e in occupational know whether reversible restriction is and SCOR Grant HL-27353 (Dr asthma Vor can we know, in retro- common in diesel exhaust overexpo- Newman). and training grant 5T ! I spect. which component parts of die- sure. however as czxs 1 and 3 dem- 32HLO 7085- 17 (DrWade). We wish I sel emissions may have been uusa- onsuate. this disorder would be easily to thank Mary Solid& RN and Re- tive. Diesel exhaust varies consider- overiooked if evaluation were limited becca Stedman for their help in case ably, containing complex, respirable to simple spirometry without bron- management and data collection. gses and paniculates to which a va- chodilator testing. Nina E3ds for her expert secretarial riety of organic compounds adsorb.'* These cases share many similarities assismnce. and our patients for their Due to this complexity and variabil- with the patients descnbed by Brooks cooperation. We thank Drs Kathleen ity, we did not >ertbrm specific and others s having reactive airways k i s s and Joseph Jamis for reviewing bonrchoprovoc~riontesting to diesel dyshncrion syndrome this manuscript. exhaust in i)ur patients. Many of the This tern has been used to describe a component pans ofdiesel exhaust can penistent clinical picture of asthma cause asthma and/or act as pulmo- nary immnts. Potentially important constitutents include oxides of nitro- g ~ n , ' ~s.ul~fur alde- resulting from a single massive exposure to an irritant gas, fume. vapor, or smoke. However, our patients worked for the nilroad for many years, and References I. NIOSH. Cucinogenic E&rs of EXPOsure lo Diesel Gar. Current Intelligence Bulletin 50. Washington, E: US De- h y d e ~ . " a.n~d carbonaceous pahcu- presumably had been chronically ex- partment of H d t h md Human Sen- lates.'s'l posed to lower levels of diesel exhaust i c s 1988::. In addition to the potential for these prior to their acute overexposum. 2. Schenker MB. Smith TJ, Muriot .A, irritants to cause airways hyperreac- One patient had 3 subacute onset of uvity, intense exposures to the oxides di- without recognizing a single Woslue SR. Speizcr E.Diesel exposure and monality among nilroad worken: results of 3 pilot study. Br 1 Ind .Wed. of nitrogen and sulfur can mult in precipitating exposure: however, re- 1984A 1:320-327. bronchiolitis obliterans.26.'2-YSymp- current. high exposures resulted in 3. Wong 0, blown RW, Kheifets L. Lu- 1, -. I: toms of dyspnea and cough generally penistent symptoms. Occupational son SR W o n o n MD. Mortality among i. I, occur several weeks after recovery ashma can develop through one of mcmben o l a h a w construction quip from exposure. Pulmonary function several postulated mechani~mr'~ ment opentors' union with potential ex- tests show a restrictive. obstructive. or While the RADS-like presentation in mixed obmctive/mtrictive pattern. our uses is compatible with an irri- posure to diesel exhaust emissions. Br 1 I ~ U.W' ed. I 9 8 5 ; ~ : 4 3 j - u a . 4. Gaschick E. Schenker MB. Muioz A. Obstructive physiology is typically tant mechanism.u it is notable that et ai. A mecontrol study oflung cancer fixed and unresponsive to bronchodi- environmental automotive exhaust and diesel exhaust exposure in d r o a d lator, unlike the reversible airways exposure has been implicated in the workcn Am Rev Rrspir Dis. 19873135: dysfunction in our patients. We can not exclude the possibility of coexistent bronchiolitis obliterans in our cases. as lung biopsy was not performed. deveiopment of allergies.* and that diesel exhaust paniculate can function as an adjuvant. enhancing antigenspecific immunoglobulin E formation in mice.4' Future studies may eluci- 1242-1248. 5. Boffena P, Harris RE. Wynder EL. Case conuul nudy on occupationd exposure to diesel exhaust and lung cmcer risk. Am 1Ind .Wed. 1990: I::571-S9 I. 6. Baniglli MC. Manella RJ. Hatch TF. Interestingly, two of our patients date the mechanism of diesel-induced Environmental and c h i d investigation exhibited physiology consistent with asthma of workmen exposed IO d i m 1 exhaust in 'reversible restricrive" lung disae.3S.36 Spirometry in c s e s 1 and 3 revealed a noma1 FEV,/FVC ratio with reduced lung volumes chamaer- istic of a classic restrictive defect. In conclusion, we have described three railroad workers who developed persistent s t h m a s 3 result of overexposure to diesel exhaust. This is the first time that any form of diesel ex- niiroad engine houm. Ind .%fedSurq. 196433:I2 I- 124. 7. Am= RG. R q e r RB. Hall DS. Chronic respiratory e k t s of exposure to d i e l emissions in coal mines. ~ r c hEnviron Holth. 1984:39:389-;94. Bronchodilator treatment, however, haust has been associated with 8. Regcr RB, Hancock J, Hankinson 1. produced 3 dramatic improvement in asthma Future studies should be per- Huri F. ,Merchant J. Coal miners expo- flow rates and normalization of lung volumes in case 1 and improved flow rates with reduced air trapping (decreased residual volume) in c s e 3 on follow-up testing. The pathophysiol- formed that can relate diesel exhaust dose and constitutents to m e s u m of airways hyperreactivity among dieselexposed workers. Regulations and work practices that rnay lead railroad sure to d i a l exhaust emissions. Ann OCCUPHyg. 1982;36:799-8 15. 9. Anfield .MD,Trabant GO.Whee!er RW. Exposure to d i d fumes and dust at 6 pomh mines. Ann Occirp Hyg. 198226: a 17-83 I . ogy of reversible restriction is un- workers to be overexposed to diesel 10. Attficld MD. The etTcct of silica 3nd known. but may relate to smooth muscle contraction and constriction J f distal respiratory bronchioles and alveolar ducts. Constection of these small terminal airways rnay preclude the development of hyperinflation exhaust should be reexamined and rectified. Acknowledgments This study was supported in pan by diesel exhaust in underground metal m d nonmetal miners. In: Kelly WD.Lee RS, eds. Indimrial fiygrrnefor .%finingm d Tunneling. Cincinnati. Ohio: .American Conference of Government;tl Industrial Hygienists: 1979: 129-135. I I . Gamble 1.Jones W . Hudak I. Merchant typically seen in asthma. We do not Physician Scientist Award ES-OO 173 J. Acute changes in pulmonary function .- 154 Diesel Asthma Wade & Newman in sait miners. In: Kclly WD. kRS. eds. Induswial HygienejOr .Mining and Tunneling. Cincinnati. Ohio: Arnaican Conference of Governmental Indwtriai Hygienists: 179:1 19-128. 12. Gamble J. J o n a WG. Respiratory effects of diesel exhaust in d t miners. Am Rev Respir Dis. 1983:128:389-394. 13. Gamble J, J o n a W, Minshall S. Epidcmioiogical-environmcntal study of d i d bus g m g c workers: chronic e f f m of diesel exhaust on the respiratory system. Envrron Res. 1987;44:6-17. 14. Kahn G. Oms P, Weeks J. Acute overexposure to diesel exhaust repon of 13 cases. Am J Ind .Wed 1988;13: 40546. 15. Ama RG. Anfield YD, Hankinson JL H a r t FJ. Rcger RB. Acute mspimtory effects of exposure to diesel miniom in coal miners. .dm Rev Respir Dis. 1982; I E39-42. 16. Gamble J, Jona W, Minshall S. Epide- miologrd-environmental diesel m d y of garage workers: acute effects of NOt and respirable p a m d a t c on the mpiratory system. Environ. Res. 198742: 201-2 14. 17. Schenker MD, SarnueIs ST, Kao NY. Hammons SK Smith TJ. Wosicic SR markers of exposure to diesei exhaust in railroad workers. Report No. 33. Cam- bridge.. Miass: Health meas Mtutc; I9901-5 1. 18. McClclIan RO,. Bicc DE.Cuddihy RG, GiiIen NA. Hendason RF, J o w RK Hcalth e f f m of d i a l exhaust.A a m o k research. risk assessment, and control strategies. In: Proceedings of [he Smnd US-Dutch International Symposium WiUiamsburg. Va, May 19, 1985: 597415. 19. Orchek I, Massari JP,Gayrard P, Gri- maud C. f i a r p i n J. Effect of short-term, low level nitrogen dioxide exposure on bronchial sensitivity of aslhmatic patients. J Clin Invest. 1976;57:301-303. 20. Ahmcd T. Marchenc B, Danta I, et d Effect of 0.1 ppm NO1 on bronchial re- activity in normais and subjects with bronchial ythma. Am Rev Respir. Dis. 1982:125:AI 52. 21. Sheppard D,Wong SW,Ueham CF,Na- del JA. Boushcy HA. Lower threshold and bronchomotor rcsponsivencss of asthmatic subjects to sulfur dioxide. Am Rev Respir Dis. 1980;122873818. Dickje HA. Niuugen dioxide-induced 22. Frank RN, Amdur MO. Warchencr J, W i n e n h e r J L mat of JNU a n - trolled exposure to so2 on raoiratory pulmonKy discasc. J Oarrp .Wed 1978: 2&103-I IO. 34. Galea M.F a d s&r dioxideinhalation. rncchania in healthy male adultsJAppl Can . U d ASSM 1. 196491:345-347. Physioi. 1962:17:252-258. 35. Hudgel DW,C00p~rD.Souhrada J. Re- 23. Utdl XU, .Morrow PE. Hydc RW.Air- vtnible r r s u i ~ i ~lueng diseax simulat- way rucrivity to sulfate and nrlttric acid ing anhma ,dnn Intern .Ued. 1976:55: aerosols in normal and YthrnaUc sub- 328-332. jccts. J .Air Poilu Control ..Lrroc 1984; 36. Giiberty R Auchinclw JH Jr. Reactive 34:931-935. h y s dyJfunction syndrome present- 24. Harkoncn H.Nordman H. Korboncn0, ing as a rcvesible d c t i v e defxt. Windblad I. Long-tmn &cas of a* Lung. 1989:16M5-6I. sure to sulhrr dioxidc Am Rev Respir 37. Brooks SM, Weiss ,MA, Bernstein IL. Dis. 1983:128:390-893. Reactive airulays dysfundon syndrome 25. C h m n NB, Y t y m CG. LaLshminar- (RADS).Chest. 1985:58:376-384. ayan S. S ~ ~ I IMC C.P~ulmouuy injuria 38. Boule! LP.Incrcaws in ainvays respon- &aud with acute sulfur dioxide in- siveness following acute exposure halation. Am Rev Respw Dir 1979;119 to respiratory irritants Chesr. 1988;94: 555-560. 47648I. 26. Woodford DM. Couru RE. GacaslcrEA. 39, Romisloff Rzr. Phan A. Lmchner FS. Obnructive lung diwyc from acuu 4- CicheIIi ,AV. R d v c Yrways dysfunc- hr dioxide exposure. Respirtxion. 1979; tion syndrome in rhrre police otfcen 38238-235. following a roadside chemical spill. 27. Brabec W. Aldehydes and acnalr In: Chesz. I99oW928-929. u,Cr;llley C d c y LV. ais Puffy'J 40. b a n S. Kipen H. Rcadve airways Indumai Hygiene and mxicniogy. dysfunction syndrome. Am F m Physi- 3rd cd New York: John Wdy, 1981: CZU. 198838:135-1 38. 2629-2669. 41. Moisan T. Prolonged asrhma after 18. Schoenbeq JB,.Mitchell C A Airway dis- smoke inhalation: 3 rrpon of thm uses eay caused by phenolic (phenolformal- and a review of previousreports. J Ocrw dehyde) resin exposure). .4mh Emiron Med. I991;33:458--)61. Heaith. 1975:30:574-577. 41. Kern DG.Outbreak of the reactive air- 29. Anderson IB.LundqvnGR RatarDF, ways dysfunction syndrome after a spill Swift DL Human raponsc tocontrolled of g l a d acetic acid. Am Rev Respir Dis. levels of inm dust. Am Rev Respir DU 199I ;134:1058-1064. 1979119619-625. 43. Luo J U . Nelscn K F&bein A. Per- 30. Ware JH, Ferris BG. Doclray DW, sistent rracrive a i w y dysfunction after Spengler JD.Suam W,S p d r n FE.P exposure to toluene diisocyanatc. Br J fects of ambient sulfur oxides and NJ. I d .Ued. 1988;47:239-241. pended particla on respiratory healthof 44. TYfo SM. Broder L .Irritant-inductd prudolcscent children. Am Rev Respir occupational asthma Chest. 1989:96: Dis. 1986;133383442. 297-300. 31. Eulm G L Abbey DE. Magic AR, H e - 45. Chan-Yeung M. Lun S. k p a t i o n a l lun JE. Chronic obstructive pulmonary asthma: state of the an.Am Rev Respir disease symptom effesrsof long-tam cu- Dis. 1986;133:686-703. mulative exposure to ambient levds of 46. Ish& T. Koizumi K. kemori R Ishi- tool suspended partlculata and sulfur yama Y.Kustubiki E. Studia of prcva- dioxide in California Scvcnth-Day Ad- lence of Japanesecedar pollinosis among ventists residenu Arch Environ Heulth. residents in a dcaxly cultivated area. 1987;42:213-222. Ann Allergy. 1987;58:265-270. 32. King TE Jr. Bronchiolitis oblitcranr In: 47. Muranaka M. Suzukj S. Koizumi T, et Schwarz MI,King TE Jr, edr Inrentitid al. Adjuvant 3ctivity of diesel-exhaust Lung Disease. Toronto: B. C. Dskcr. particulates for the production of IgE 1988:325-342. antibody in mice. J Allergy CIin Immu- 33. Horvath EP. Colic0 DGA. Barbee RA. noi. 1986;77:616-623.