Occupational lung disease * 7Series editor: P S Burge

Comparison of soybean epidemic asthma andoccupational asthma

Josep M Anto, Jordi Sunyer, Anthony J Newman Taylor

Asthma is an important public health problembecause of its increasing prevalence and as-sociated morbidity. It is a major research issuebecause its aetiology is not established andthe reasons for its increasing occurrence areunknown. Occupational asthma is a valuablemodel of asthma caused by specific environ-mental exposures which could be useful for abetter understanding of the disease.' Retro-spective and prospective studies have shownthat, for most of its causes, occupational asthmaoccurs during the first two years of exposure.Both the intensity and timing of exposure havebeen found to be risk factors for occupationalasthma. Prospective investigations in labor-atory animal workers have found a higher pre-valence ofnew work-related symptoms in thoseexposed to higher airborne concentrations ofantigen. Factors such as atopy and smokinghave been reported to increase the risk of somecauses of occupational asthma. Long term fol-low up of patients with occupational asthmahas shown persisting symptoms, airways hyper-responsiveness, and evidence of sensitisationmany years after avoidance of exposure to theinitiating cause.A similar pattern of interrelationships has

been observed in soybean epidemic asthma.2In November 1979 soybean started to be un-loaded in the harbour of Barcelona and, in1981, the first asthma outbreak was described.Asthma outbreaks were repeatedly identifieduntil 1987 when it was established that soybeanunloaded at a particular silo was the causalagent. The unloading of soybean was stoppeduntil appropriate filters had been installed in theresponsible silo. This intervention preventedfurther outbreaks of asthma. Several studieshave been conducted to assess the magnitudeand characteristics of the epidemic as well asits aetiology. Current evidence suggests thatsoybean epidemic asthma is a useful model ofcommunity asthma which has many similaritiesto occupational asthma. In this review we havecompared the characteristics of soybean epi-demic asthma and occupational asthma, withspecial emphasis on the nature of the risk fac-tors for both conditions.

Initial step: from the identification ofoutbreaks to the soybean hypothesisIn Barcelona asthma outbreaks were first iden-tified in 1981 by a sudden and massive influx

of patients with acute severe asthma seekingmedical attention at the emergency room of alarge teaching hospital. A retrospective analysiscarried out in 1983 identified six outbreaksalthough evidence for the aetiology of the out-breaks was lacking. In 1984 a collaborativeasthma group formed by epidemiologists andclinicians from the main hospitals of the citywas established by the Department of PublicHealth. All available evidence was reviewed anda prospective monitoring system for respiratoryemergency room admissions was developed,with the participation of the emergency de-partments of the four largest hospitals whichaccounted for 76% of all emergency room ad-missions for asthma in Barcelona. In all patientswith asthma or chronic obstructive pulmonarydisease admitted to the emergency room thefollowing data were recorded: age, sex, address,date of admission, hour of arrival, and outcome(referral or discharge). A standardised ques-tionnaire was developed for asthmatic patientsaffected on particular (possibly epidemic) days.Between 1981 and 1986 a total of 12 out-

breaks of asthma were identified. A study ofthese outbreaks revealed that most asthma at-tacks lasted for short periods - usually lessthan four hours - and occurred in the districtsnearest to the harbour, adjacent to a largeindustrial area. The presence of a simultaneoustime and geographical cluster suggested a pointsource epidemic,3 and the hypothesis was pro-posed that asthma outbreaks were due to in-halation of a biological or chemical substanceintermittently emitted from a point source inthe harbour or its vicinity. Repeated efforts,however, failed to identify the point source.Although an association between asthma out-breaks and peaks in nitrogen dioxide was sug-gested, no significant impairment of patientswith epidemic asthma was observed during anair pollution episode in which maximum hourlymeans of nitrogen dioxide and sulphur dioxideof 846 and 810,g/m3, respectively, were re-corded.4

Despite systematic efforts to identify en-vironmental events potentially related to theoccurrence of asthma outbreaks, a plausiblehypothesis was not developed until the firstmonths of 1987 when the harbour ad-ministration recognised that at least three out-breaks had occurred on days when soybean

Departmentd'Epidemiologia iSalut Publica,Institut Municipald'Investigaci6 Medica(IMIM),Universitat Autonomade Barcelona,E-08003 Barcelona,SpainJ M Ant6J Sunyer

Department ofOccupational andEnvironmentalMedicine,National Heart andLung Institute,London, UKA J Newman Taylor

Correspondence to:Dr J M Ant6.

743Thorax 1996;51:743-749

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Ant6, Sunyer, Newman Taylor

was unloaded. The presence of specific IgEantibodies against 22 different commercial anti-gens including soybean was assessed in a panelof 18 serum samples from patients affectedin at least two asthma epidemics. Measurablelevels of IgE against soybean were detected in13 ofthe 18 samples, whereas measurable levelsto any of the remaining allergens were onlydocumented in three samples.Although this preliminary association lacked

strength and consistency, cessation of soybeanunloadings was recommended during anasthma outbreak that occurred in September1987.

Investigation of the soybean hypothesisand interventionThe soybean hypothesis was confirmed by theresults oftwo different epidemiological studies:a time series study of asthma outbreaks5 and acase-control study of epidemic patients.6The first study5 assessed the association be-

tween unloading of 26 products from shipsin the harbour and the occurrence of asthmaoutbreaks for the period 1985-6. All 13 asthmaepidemic days during these two years coincidedwith the unloading of soybean; in contrast, noasthma epidemics occurred in the remaining468 days on which soybean was not unloaded.Moreover, there were two silos in the harbour(silo A and silo B), and it was found that 12of the 13 outbreaks occurred during unloadingof soybean at silo A, whereas only one outbreakhad occurred during unloading of soybean atsilo B. Of the remaining 25 products, onlywheat was associated with asthma epidemics -

but concurrently with soybean unloading. Itwas appreciated that the lack of bag filters atthe top of silo A permitted the release ofsoybean dust into the air.

In the case-control study6 serum sampleswere taken from 86 patients seen at the emer-gency room on a particular epidemic day. Con-trols were selected from emergency roomadmissions for asthma on non-epidemic days.A total of 86 controls were matched by age,sex, and area of residence. Specific IgE levelsagainst soybean and other common allergenswere measured by RAST, and 74-4% of caseswere found to have increased binding to com-mercial soybean extract compared with 4-6%of controls (odds ratio (OR) =61). Westernblot and thin layer electrofocusing/blottedradioimmunoelectrofocusing showed that, onepidemic days, IgE of patients with asthmabound strongly to glycoprotein bands of mo-lecular weight <14-4 kD and isoelectric point<6, which appeared to be the major allergens.7The unloading of soybean in silo A was

temporarily interrupted in September 1987.Three months later, bag filters were installedat the top of the silo and soybean unloadingresumed under controlled conditions. Fol-lowing this intervention there was a mean 10-fold reduction in soybean aeroallergen con-centrations and 100-fold reduction in peaklevels. The number of referrals from emergencyrooms to intensive care units showed a 25-folddecrease. No asthma outbreaks have occurred

since the intervention,8 whereas on epidemicdays between 1981 and 1987 there had been26 asthma outbreaks with 687 emergency roomvisits for asthma.

Risk factors for soybean epidemicasthma and occupational asthmaAlthough these studies allowed identificationof the cause of the asthma outbreaks, they didnot provide information about other individualrisk factors. Current evidence of the role of riskfactors other than soybean - that is, exposure,sex, age, atopy, and smoking - as well as theevidence on these factors from studies of oc-cupational asthma, are reviewed in this section.

INTENSITY OF EXPOSUREDirect assessment of the levels of soybeanallergen on epidemic days was obtained froma study of samples collected from air filtersinstalled in Barcelona.9 Of a total of 38 dayssampled, 22 corresponded to the period whenthe cause of outbreaks was still unknown andthe remaining 16 occurred after the installationof bag filters at silo A. Air samples were pro-cessed by gas chromatography and combinedgas chromatography/mass spectrometry. Themean concentration of soybean esterols was5-15 times higher on epidemic days than onnon-epidemic days. In addition, soybean al-lergens were eluted from 16 fibreglass filtersheets and assayed by RAST inhibition. Be-cause it was not possible to express allergenconcentration in mass units, an arbitrary valueof 106 units was assigned to the referencesoybean husk extract, one unit containing ap-proximately 1 ng of allergen. Epidemic daysshowed varying levels of soybean allergen from1600 to 10600 U/m3, whereas on non-epi-demic days the range was 0-3-320 U/m3. Thelevels on epidemic days were below the max-imum concentrations of aeroallergens reportedby Reed et all' in various occupational workplaces (range <10 ng/m3 to 36 000 ng/m3).

SEXNo differences according to sex were observedin particular outbreaks. However, in a case-control study" cases were more likely to bemen than were controls, although the increasedrisk for men was not significant (OR= 1 3;95% confidence interval (CI) 0 7 to 2 1) afteradjustment for age and smoking. Attack rateson soybean epidemic asthma days reportedin Cartagena, Spain did not show differencesbetween men and women."2 Thus, there wasno evidence that sex per se was associated withan increased risk of soybean epidemic asthma.

In occupational asthma sex has been con-sidered a less important risk factor since workforces often consist predominantly of eithermen or women;'3 furthermore, both are likelyto be involved in different jobs within the samefactory with the possibility of confounding byexposure. In a study of laboratory animalworkers in a pharmaceutical company'4 60% ofthe symptomatic group were women compared

744

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Comparison of soybean epidemic asthma and occupational asthma

with 31% in the group without symptoms.Respiratory symptoms related to work withanimals were reported by 16% of women and7-3% of men. Given that the association be-tween sex and the risk of occupational asthmawas not formally assessed, differences couldhave been due to the fact that 41% of womenwere in the exposure category with mostfrequent and intense exposure to animals.In a survey of workers exposed to tetra-chlorophthalic anhydride (TCPA) the pre-valence of sensitisation to TCPA was similarin both sexes.'5 Studies on occupational asthmado not usually provide sufficient informationto exclude a differential risk of either sens-itisation or work-related respiratory symptomsby sex. Nonetheless, studies of soybean epi-demic asthma and occupational asthma studiesdo not suggest that sex is an independent riskfactor for asthma.

AGEThe risk of suffering soybean epidemic asthmaincreased with age. In a descriptive study of anasthma outbreak'6 the ratio of attack rates onepidemic days to control periods showed anincreasing magnitude with increasing age (2.42,2-88, 6-58, 8-70, for those aged <14, 15-44,45-64, and >65 years, respectively). A similartrend was also observed in the other outbreaks.In a case-control study," after adjustment forskin reactivity, total IgE, sex, smoking, andexposure, there was a consistent associationbetween age and epidemic asthma (OR 1 9(95% CI 1 1 to 3 6) and 2-8 (95% CI 1-4 to6 0)) for patients aged 45-64 years and those>64 years, with subjects of <45 years servingas a reference category. After the installationof bag filters at the harbour silo the reductionin the mean number of emergency room ad-missions for asthma was higher in the oldergroups.8 The proportional reduction in thedaily mean of emergency room admissions forasthma after the intervention was 26% for menaged 15-44 years, 60% for those aged 45-64years, and 62% for those >64 years. Figuresfor women in the same groups were 20%, 31 %,and 33%, respectively.These observations, however, contrast with

the current understanding that the incidenceof asthma is higher during childhood and thatit is more likely to be non-allergic in those whodevelop it after 40 years of age. Given anhomogeneous attack rate and severity, it ispossible that, in our studies, older patients withepidemic asthma would have been more likelyto attend the emergency room on epidemic daysthan younger patients. Unfortunately, based onthe data available, this possibility cannot beexcluded. On the other hand, it has been sug-gested that the elderly might be less able totolerate exposure to novel allergens, either be-cause of reduced immunological tolerance oraccumulated exposure to modifying factorssuch as cigarette smoking which increase therisk of sensitisation.1As pointed out by Becklake,"3 age has rarely

been considered an important risk factor foroccupational asthma, with age ranges within

working populations restricted to adulthoodand from which elderly people are excluded.Using the SWORD voluntary reporting schemein the UK, Meredith'8 has shown an increasingincidence of occupational asthma with in-creasing age. The standardised rate ratio inmen increased from 0-80 in those aged 16-29years to 1X24 in those >44 years. The cor-responding ratios in women were 0-64 and1 40. This age pattem was more pronouncedafter adjusting for occupation. Although theage pattem was consistent for all occupationalcategories, the author suggested that older casesmight be more likely to report asthma or to benotified, but could not exclude the possibilityof risk increasing with increasing age. In tworecent prospective studies of occupationalasthma in laboratory animal and bakeryworkers,'920 we have assessed whether or notthe risk for asthma is increased with increasingage (unpublished results). In both studies, afteradjusting for intensity ofexposure and smoking,the risk of developing respiratory symptomsafter employment was slightly higher in theyounger workers, contrary to this hypothesis.In summary, although there is no consistentevidence of an increased risk of occupationalasthma with increasing age, the possibilityneeds further assessment in studies of bothepidemic asthma and occupational asthma.Whereas most ofthe studies carried out in the

Westem world have shown that the incidence ofasthma peaks before the teenage years, datafrom tropical countries appear to differ. Rossreported that, for both men and women, thepeak of asthma incidence was in the fourthdecade with men showing a second peak be-tween the ages of 50 and 60.21 This age pattemis consistent with the report by Woolcock fromNew Guinea which showed that the prevalenceof asthma was 7-3% in adults and only 06%in children.22 It has been suggested that a lowprevalence ofasthma in childhood in developingcountries may be due to a high prevalence ofviral infections in early life with a selective en-hancement on the development of Thl-typecells, subsequent inhibition of both Th2-likeclones, and allergic sensitisation.23 However, thetrue explanation for the different age of onset ofasthma in different latitudes and its relationshipwith the age pattern of the Barcelona soybeanasthma epidemic remains obscure.

ATOPY (SERUM OR SKIN REACTIVITY TOCOMMON INHALANT ALLERGENS)Atopy, defined as a positive reaction to skin testsor the presence of circulating IgE antibodies tocommon aeroallergens, was a risk factor forsoybean epidemic asthma. In a case-controlstudy6 specific IgE was measured againstDermatophagoides, Parietaria, and Aspergillus.Patients with epidemic asthma were four timesmore likely than controls to react to any ofthese allergens (OR 4-1; 95% CI 1-7 to 10-7);Parietaria showed the strongest association withepidemic asthma (OR 9; 95% CI 1 7 to 111 6).Serum levels of specific IgE against legumeswere also measured in a subset of patients whohad been admitted to hospital on more than

745

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Ant6, Sunyer, Newman Taylor

Relationship between epidemic asthma and airborne exposure to soybean (measured as thearea of residence of daily walking expressed in km), according to atopy (number ofpositive skin reactions) and smoking

Airborne soybean Skin test Non-smokers Smokersexposure

Odds ratio 95% CI Odds ratio 95% CI

>4 0 1 0 1-5 0.3 to85<4 0 1-4 0-3 to 6 5 2-9 0-6 to 15 5>4 > 1 2-4 0 6 to 5 2 3-2 0-7 to 15 6<4 > 1 2-8 0 7 to 12.2 7 9 1 8 to 36-0

Adapted from Sunyer et al. "

one epidemic asthma day. IgE antibodies to

pea, peanut, and white bean were observed in10%, 15%, and 10% of cases and in 11%, 5%,and 5% of controls.Atopy and epidemic asthma were also

studied in a case-control study with 18 in-dividually matched pairs in Cartagena (Spain)where soybean asthma outbreaks have beenreported.'2 When skin test reactions to commoninhalant allergens were considered, cases re-

acted slightly more frequently to other allergensalthough the differences did not reach sig-nificance, possibly because of the small numberof subjects.

It has been shown that atopy is a risk factorfor sensitisation and work-related respiratorysymptoms in bakery workers,24 and for thoseworking with platinum salts,25 laboratory an-

imals,20 and detergent enzymes.26 In a study of279 bakery workers a high prevalence (33%)of sensitisation to storage mites was found.Among those who were atopic, 37-52% had a

positive skin prick test to storage mites com-

pared with only 6-7% of non-atopic workers,a similar difference being observed for wheatand flour allergens.24 In a study of individualsworking with laboratory animals asthma de-veloped in 34-3% of atopic and 2-7% of non-

atopic workers.27 In platinum refinery workersthe risk of occupational asthma for atopic sub-jects, after adjusting for smoking, was more

than twice that for non-atopic subjects, al-though statistically significant differences were

not found, probably because the sample sizewas too small.20 In general, both high and lowmolecular weight agents causing occupationalasthma which are associated with specific IgEantibody cause sensitisation more frequently inatopic than in non-atopic workers. In contrast,atopy is not a predisposing factor for low mo-

lecular weight chemicals not associated withspecific IgE which cause asthma such as iso-cyanates and Western red cedar.28

SMOKINGFollowing reports which suggested that smok-ing was a risk factor for occupational asthma,28the hypothesis was tested in soybean epidemicasthma." Smokers were more likely to sufferfrom epidemic asthma than non-smokers re-

gardless of the degree of exposure or atopy to

soybean. The smoking-related risk was highestamong those patients who lived near to thepoint source and had positive skin test re-

sponses to common aeroallergens. There was

an interaction between exposure, atopy, andsmoking (OR 7 9 compared with the reference

category after adjusting for age and sex; table).When the smoking status was considered inrelation to the period of time when the asthmaoutbreaks occurred, those who were smokers,lived in the proximity of the point source, andwere atopic showed an OR of 9-6 (95% CI 0-9to 169) compared with 2-5 (95% CI 0.2 to50-6) in those who had stopped smoking beforethe start of the epidemics. When the previousanalysis was restricted to atopic subjects withexposure to airborne soybean there was anassociation between the number of pack yearssmoked and risk of epidemic asthma (OR 12-6;95% CI 1-3 to 114-5 for those who had smokedmore than 33 pack years).

Occupational studies have shown that smok-ing is a risk factor for sensitisation in workersexposed to platinum salts,25 tetrachlorophthalicanhydride,'5 and in ispaghula and green coffeeworkers.29 Smoking has also been reported toincrease the risk of respiratory symptoms inlaboratory animal workers'4 and in workers whoprocess snow crabs.30 In the study of platinumrefinery workers the risk ofdeveloping a positiveskin test to platinum salts was 5-6 times greateramong smokers than non-smokers, and therisk for respiratory symptoms doubled per 10cigarettes/day.25 In contrast, smoking has notbeen found to be a risk factor for occupationalasthma not associated with specific IgE suchas Western red cedar.28 Our finding that ex-smokers were at lower risk of soybean epidemicasthma may be due to chance, although asimilar result was reported in subjects whodeveloped specific IgE when exposed tohumidifier antigens.3' Smoking is a riskfactor for both soybean epidemic asthma andoccupational asthma; the implications of thesefindings in relation to the development of pre-ventive strategies are important.

Natural history of epidemic andoccupational asthmaLATENCY PERIODSoybean was initially unloaded in November1979 and the first asthma outbreak was iden-tified about 20 months later in August 1981.This 20 month period should be considered asthe upper limit of the latency period as nosystematic investigation of outbreaks was car-ried out before 1985. This is a latency periodfor the whole population as individual in-formation on the period which had elapsedbetween the first exposure to soybean dust andthe first epidemic attack is not available. This20 month period, however, is consistent withan average interval of 1-3 years in the onset ofoccupational asthma after initial exposure."' Ina study of workers exposed to laboratory ratsthe median duration of employment before theonset of new work-related symptoms was oneyear, with a range from less than one monthto 11 years.20 In a historical cohort study of92 platinum refinery workers the incidenceof respiratory symptoms and sensitisation toplatinum salts was highest during the first yearof employment, with no symptoms or positiveskin tests being recorded after four years ofexposure.25

746

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Comparison of soybean epidemic asthma and occupational asthma

FATAL AND NEAR-FATAL ASTHMA EPISODESAll deaths due to asthma or other causes thatoccurred in patients with epidemic asthma on

epidemic days were monitored, and at least 26such deaths were identified. In addition, more

than 50 admissions to intensive care units oc-

curred on epidemic days. A total of 687 cases

were recorded at emergency room departmentson all epidemic days, so this represents a

high case fatality rate. The clinical course ofnear-fatal soybean epidemic asthma has beenreported elsewhere.32 A recent immuno-histochemical study has suggested that a lackofCD3 and CD8 in the mucosa and submucosaof lung specimens in patients who died fromsoybean asthma could be a specific marker ofthis condition.33 In contrast to soybean epi-demic asthma, deaths among cases of oc-

cupational asthma have been reported onlyrarely. The low rate ofmortality in occupationalasthma was noted by Fabbri et al34 in a reportof a 43 year old car painter who died withinone hour of exposure to a polyurethane paintin the work place.The contrast between the reported mortality

from soybean and occupational asthma is strik-ing, and several explanations can be proposed.Firstly, death from occupational asthma may

not be recognised - for example, a suddendeath may be attributed to a different conditionfrom asthma such as myocardial infarction or,

because of its legal or economic implications,it may not be reported. Secondly, the higherfatality rate in epidemic asthma could be relatedto exposure since the airborne concentrationsof soybean may have been substantially higherthan are usual in occupational asthma. How-ever, indirect estimation of exposure levels dur-ing the asthma epidemics showed that the levelsof soybean allergen were similar to those re-

ported in occupational settings. The patternof exposure could be more important thanintensity alone; intermittent high exposure totoluene diisocyanate was associated with a

higher risk of developing work-related asthmathan continuous exposure to a lower con-

centration.35 Short term high exposures afteran exposure-free window may have occurredin Barcelona during the unloading of soybeanand could have been associated with a highercase fatality rate in epidemic asthma. It is pos-sible that soybean allergen is a more potentallergen than those usually present in oc-

cupational settings. It is also possible thatpatients with soybean epidemic asthma, whoare predominantly older and often with a pre-

vious history of asthma, were at a higher risk ofdeath when exposed to soybean than relativelyyounger and healthier working populations.

Evolution of epidemic asthma after anintervention

IMPROVEMENT OF ASTHMA SYMPTOMSA relevant question is the extent to whichepidemic patients might be expected to im-prove after an intervention that reduced ex-

posure levels sufficiently to prevent furtherasthma outbreaks. Unfortunately, informationon patients with epidemic asthma is not avail-

able from before the soybean asthma outbreaks,so only a post-intervention assessment is pos-sible.The case-control study described earlier'1

was used for this purpose.36 The cases com-prised a random sample of asthmatic patients(n =213) affected in one or more of the 26asthma epidemics, and controls were a randomsample of asthmatic patients admitted to theemergency room with attacks of asthma onnon-epidemic days (n = 170). The study wascarried out two years after the last epidemic.

Patients with epidemic asthma showed con-sistently fewer asthma symptoms during thepreceding 12 months, although statistically sig-nificant differences were only found for "tight-ness in the chest", and had been admitted tothe emergency room during the previous yearwith acute attacks of asthma less frequently(20A4%) than non-epidemic asthma patients(36-7%) (p<0 001).

Baseline spirometric tests in cases and con-trols showed airways limitation of moderateintensity and no statistically significant differ-ences were found in ventilatory capacity. Nodifferences were found between the two groupsin baseline forced expiratory volume in onesecond (FEVI) when stratified by age, sex, andsmoking habit. The proportion who showed afall in FEV, of >20% of baseline at each doseof methacholine was similar in both groups.With regard to treatment taken at the time

of the study, no differences were found inthe types of drugs taken, except for inhaledcorticosteroids which were used by fewerpatients with epidemic asthma than controls(34 3% versus 49%; p<0 01).

In a separate study8 we found that two yearsafter the last epidemic 52% of 142 patientsadmitted to an emergency room during asoybean asthma outbreak had measurable levelsof IgE against soybean. In 38 patients it waspossible to match serum samples obtained be-fore and two years after the intervention. Themean serum concentration of specific IgE haddecreased from 2 PRU/ml before the inter-vention to 1 PRU/ml after the intervention(p<0001). A logistic regression analysis iden-tified no relationship between the rate of de-crease in the serum concentration of specificIgE and age, sex, total IgE, and proximity ofthe patient's residence to the soybean pointsource.

Persistence of airway symptoms, hyper-responsiveness, and evidence of sensitisationfor years after avoidance of exposure has beenreported in studies of the outcome of oc-cupational asthma. In a four year follow up ofTCPA-induced asthma37 persistence of bothspecific IgE and symptoms after TCPA avoid-ance was observed. Specific IgE decreased ex-ponentially with a half life of one year. Allworkers had a positive skin test to TCPA,showing a decrease in the weal size on eachoccasion that they were tested. All sevenpatients reported that their asthma had im-proved since leaving the factory, but they stillreported symptoms which required treatmentin five cases. Malo et al38 reported a follow upof 31 snow crab workers who showed a similar

747

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Ant6, Sunyer, Newman Taylor

decreasing pattern of specific IgE with levelsstill decreasing two years after leaving the workplace. These studies have extended earlierretrospective studies39 which showed that 30-100% of workers who develop occupationalasthma continue to have symptoms and non-specific bronchial responsiveness at the end ofthe follow up period (1-11 years).

Since occupational asthma can lead to per-manent disability, it is important to know whichfactors are associated with a worse prognosis.Current evidence suggests that continued ex-posure after the onset of symptoms and severityof asthma at diagnosis are associated with aworse evolution after avoidance of exposure.Atopy and smoking, however, have not beenimplicated in the persistence of occupationalasthma. Future studies in both epidemic andoccupational asthma could improve our know-ledge of the relevant factors.

Epidemic versus occupational asthma:similarities and differencesWe here consider the similarities and differ-ences between epidemic and occupationalasthma and the way in which these could affectprevious comparisons.Among the similarities the most important

relates to the novelty of exposure. In bothepidemic and occupational asthma a givenpopulation is exposed to a novel allergen froma particular point of time. This important timesequence is usually well established in studies ofepidemic and occupational asthma and allowsidentification of a causal relationship. Studiesof occupational and soybean epidemic asthmahave been able to assess aetiological modelswhich have included risk factors such as atopyand smoking, providing a more complete know-ledge of the aetiology. In addition, other im-portant features such as the latency intervaland the intensity of exposure are amenable toobservation in both occupational and soybeanepidemic asthma. A proportion of patients withepidemic asthma experienced asthma attacksduring outbreaks in areas far from the soybeanpoint source, similar to occupational asthmawhere a worker may develop asthma withoutbeing directly exposed. Clearcut avoidance ofexposure has allowed investigation of the sub-sequent evolution ofthe disease in occupationaland soybean epidemic asthma; sensitisation,airways hyperresponsiveness, and symptomsmay persist for long periods of time, if notindefinitely, after avoidance of exposure. Thefact that soybean epidemic asthma and mostcases of occupational asthma are associatedwith specific IgE adds biological coherence tothe comparative review presented here.

In contrast, some relevant differences shouldbe highlighted. Soybean epidemic asthma in-volved the exposure of a total community,whereas occupational asthma reflects the ex-posure of a selected working population. Atleast two consequences arise from this differ-ence. Firstly, the important finding that chil-dren were only rarely affected by soybeanepidemic asthma cannot be tested for oc-cupational asthma and, similarly, it is difficult

to test whether older workers are at a higherrisk of occupational asthma as was the case inthe soybean epidemic asthma because of thelimited age range of working populations andtheir possible assignation to lower exposures.Secondly, the healthy worker effect may reducethe risk of developing occupational asthma,whereas in epidemic asthma those with pre-vious asthma may well have been more sus-ceptible to soybean allergy. Finally, allergensare not inhaled as isolated particles but ascomplex aerosols which may differ both be-tween occupational and epidemic asthma andbetween different occupational exposures.

Dr Josep M Ant6 was Visiting Principal Fellow at the NationalHeart and Lung Institute, Royal Brompton Hospital, London,UK in receipt of a grant from Fondo de Investigaci6n Sanitaria(1994) (FIS-945838), Spain.

1 Newman Taylor AJ. Environmental determinants ofasthma.Lancet 1995;345:296-9.

2 Ant6 JM, Sunyer J. Epidemiologic studies of asthma epi-demics in Barcelona. Chest 1990;98:185-90s.

3 Knox EG. Epidemics of rare diseases. Br Med Bull 1971;27:43-7.

4 Ant6 JM, Sunyer J, Plasencia A. Nitrogen dioxide andasthma outbreaks. Lancet 1986;ii:1096-7.

5 Ant6 JM, Sunyer J, Rodriguez-Roisin R, Surriez-Cervera M,Vazquez L, and The Clinical and Toxico-epidemiologicalCommittee. Community outbreaks of asthma associatedwith inhalation of soybean dust. N EnglJ3 Med 1989;320:1097-102.

6 Sunyer J, Ant6 JM, Rodrigo MJ, Morell F, and The Clinicaland Toxicoepidemiological Committee. Case-controlstudy ofserum immunoglobulin-E antibodies reactive withsoybean in epidemic asthma. Lancet 1989;i:179-82.

7 Rodrigo MJ, Morell F, Helm RM, Swanson M, Greife A,Ant6 JM, et al. Identification and partial characterizationof the soybean dust allergens involved in the Barcelonaasthma epidemic. JAllergy Clin Immunol 1990;85:778-84.

8 Ant6 JM, Sunyer J, Reed ChE, Sabria J, Martinez F, MorellF, et al. Preventing asthma epidemics due to soybeans bydust-control measures. N Engl J Med 1993;329: 1760-3.

9 Aceves M, Grimalt JO, Sunyer J, Ant6 JM, Reed CE.Identification ofsoybean dust as an epidemic asthma agentin urban areas by molecular marker and RAST analysisof aerosols. J AllerDg Clin Immunol 199 1;88: 124-34.

10 Reed ChE, Swanson MC, Li JTC. Environmental mon-itoring ofprotein allergens. In: Bernstein IL, Chang-YeungM, Malo JL, Bernstein DI, eds. Asthma in the workplace.New York: Marcel Dekker, 1993:249-75.

11 Sunyer J, Ant6 JM, Sabria J, Rodrigo MJ, Roca J, MorellF, et al. Risk factors of soybean epidemic asthma. Therole of smoking and atopy. Am Rev Respir Dis 1992;145:1098-102.

12 Hernando L, Navarro C, Marquez M, Zapatero L, GalvanF. Asthma epidemics and soybean in Cartagena (Spain).Lancet 1989;i:502.

13 Becklake MR. Epidemiology: prevalence and determinants.In: Bernstein IL, Chan-Yeung M, Malo J-L, BernsteinDI, eds. Asthma in the workplace. New York: MarcelDekker, 1993:29-59.

14 Venables KM, Upton JL, Hawkins ER, Tee RD,Longbottom JL, Newman Taylor AJ. Smoking, atopy, andlaboratory animal allergy. Br Ind Med 1988;45:667-71.

15 Venables KM, Topping MD, Howe W, Luczynska CM,Hawkins R, Newman Taylor AJ. Interaction of smokingand atopy in producing specific IgE antibody against ahapten protein conjugate. BMJ 1985;290:201-4.

16 Ant6 JM, Sunyer J, and The Asthma Collaborative Groupof Barcelona. A point-source asthma outbreak. Lancet1986;i:900-3.

17 Hendrick DJ. Asthma: epidemics and epidemiology. Thorax1989;44:609-13.

18 Meredith S. Reported incidence of occupational asthma inthe United Kingdom, 1989-90. _f Epidemiol CommunityHealth 1993;47:459-63.

19 Cullinan P, Lowson D, Nieuwenhuijsen MJ, Sandiford C,Tee RD, Venables KM, et al. Work related symptoms,sensitisation, and estimated exposure in workers not pre-viously exposed to flour. Occup Environ Med 1994;51:579-83.

20 Cullinan P, Lowson D, Nieuwenhuiisen MT, Gordon S,Tee RD, Venables KN, et al. Work related symptoms,sensitisation and estimated exposure in workers not pre-viously exposed to laboratory rats. Occup Environ Med1994;51:589-92.

21 Ross I. Bronchial asthma in Malaysia. BrJ Dis Chest 1984;78:369-75.

22 Woolcock AJ, Dowse GK, Temple K, Stanley H, AlpersMP, Tumer KJ. The prevalence of asthma in the South-Fore people of Papua New Guinea. A method for fieldstudies of bronchial reactivity. Eur J Respir Dis 1983;64:571-81.

748

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from

Comparison of soybean epidemic asthma and occupational asthma

23 Martinez F. Role of viral infections in the inception ofasthma and allergies during childhood: could they beprotective? Thorax 1994;49:1189-91.

24 Tee RD, Gordon DJ, Gordon S, Crook B, Nunn AJ, MuskAW, et al. Immune response to flour and dust mites in aUnited Kingdom bakery. BrJ Ind Med 1992;49:581-7.

25 Venables KM, Dally MB, Nunn AJ, Stevens JF, StephensR, Farrer N, et al. Smoking and occupational allergy inworkers in a platinum refinery. BMJ 1989;299:939-42.

26 Bernstein IL. Enzyme allergy in populations exposed tolong-term, low-level concentrations of household laundryproducts. Allergy Clin Immunol 1972;49:219-37.

27 Slovak AJM, Hill RN. Does atopy have any predictive valuefor laboratory animal allergy? A comparison of differentconcepts of atopy. Br Ind Med 1987;44: 129-32.

28 Chan-Yeung M, Lam S. Occupational asthma. Am RevRespir Dis 1986;133:686-703.

29 Zetterstrom 0, Osterman K, Machado L, Johansson SGO.Another smoking hazard: raised serum IgE concentrationand increased risk of occupational allergy. BMJ 1981;282;1215-7.

30 Cartier A, Malo JL, Forest F, et al. Occupational asthma insnow crab-processing workers. Allergy Clin Immunol1984;74:261-9.

31 Finnegan MJ, Little S, Gordon DJ, Austwick PKC, TeeTD, Nunn AJ, et al. The effect of smoking on the de-velopment of allergic disease and specific immunologicalresponses in a factory workforce exposed to humidifiercontaminants. Br _' Ind Med 199 1;48:30-3.

32 Ferrer A, Torres A, Roca J, Sunyer J, Ant6 JM, Rodriguez-Roisin R. Characteristics of patients with soybean dust-induced acute severe asthma requiring mechanical vent-ilation. Eur Respir 1990;3:429-33.

33 Synek M, Ant6 JM, Beasley R, Friew AJ, Holloway L,Lampe FC, et al. Immunopathology of fatal soybean dust-induced asthma. Eur RespirJ7 1996;9:54-7.

34 Fabbri LM, Danieli D, Crescioli S, Bevilacqua P, Meli S,Saetta M, et al. Fatal asthma in a subject sensitized totoluene diisocyanate. Am Rev Respir Dis 1988; 137: 1494-8.

35 Weill H, Butcher B, Dharmarajan V, et al. Respiratory andimmunologic evaluation ofisocyanate exposure in a new manu-facturing plant. Cincinnati: US Department of Health andHuman Services, 1981 (NIOSH technical report).

36 Sabria J, Ant6 JM, Sunyer J, Roca J, Morell F, Rodriguez-Roisin R, et al. Clinical and functional characteristics ofpatients two years after being affected by the soybeanasthma epidemic in Barcelona. Thorax 1994;49:906-9.

37 Venables KM, Topping MD, Nunn AJ, Howe W, NewmanTaylor AJ. Immunologic and functional consequences ofchemical (tetrachlorophthalic anhydride)-induced asthmaafter four years of avoidance of exposure. Allergy ClinImmunol 1987;80:212-8.

38 Malo J-L, Ghezzo H, D'Aquino C, L'Archeveque J, CartierA, Chan-Yeung M. Natural history of occupationalasthma: relevance of type of agent and other factors inthe rate of development of symptoms in affected subjects.JAllergy Clin Immunol 1992;90:937-44.

39 Chan-Yeung M, Malo J-L. Natural history of occupationalasthma. In: Berstein IL, Chan-Yeung M, Malo J-L,Bernstein DI, eds. Asthma in the workplace. New York:Marcel Dekker, 1993;299-311.

749

on February 12, 2022 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.51.7.743 on 1 July 1996. D

ownloaded from