Occupational and Environmental Medicine 1997;54:335-342

Latex allergy: epidemiological study of 1351hospital workers

Gary M Liss, Gordon L Sussman, Ken Deal, Shirley Brown, Maureen Cividino,Sidney Siu, Donald H Beezhold, Gordon Smith, Mark C Swanson, John Yunginger,Andrew Douglas, D Linn Holness, Phyllis Lebert, Paul Keith, Susan Wasserman,Kristiina Turjanmaa

Ontario Ministry ofLabour, Ontario,CanadaG M LissS SiuG SmithDepartment ofPreventive Medicineand Biostatistics,University ofToronto,Toronto, CanadaG M LissDivision ofAllergy,Wellesley Hospital,University of Toronto,Toronto, Ontario,CanadaG L SussmanMichael G DeGrootSchool of Business,McMaster University,Hamilton, Ontario,CanadaK DealEmployee HealthService, HamiltonCivic Hospitals,Hamilton, Ontario,CanadaS BrownM CividinoGuthrie ResearchInstitute, Sayre,Pennsylvania, USAD H BeezholdAllergic DiseasesResearch Laboratory,Mayo Clinic,Rochester, Minnesota,USAM C SwansonJ YungingerMedical DevicesBureau, HealthCanada, Ottawa,Ontario, CanadaA DouglasDepartment ofOccupational andEnvironmental Health,St Michael's Hospital,University of Toronto,Toronto, Ontario,CanadaD L HolnessDepartment ofMedicine, McMasterUniversity, Hamilton,Ontario, CanadaP LebertP KeithS WassermanDepartment ofDermatology,University Hospital,Tampere, FinlandK TurjanmaaCorrespondence to:Dr Gary M Liss, Health andSafety Studies Unit, OntarioMinistry of Labour, 7thFloor, 400 UniversityAvenue, Toronto, ON,Canada M7A 1T7.Accepted 20 November 1996

AbstractObjectives-To determine the prevalenceof latex sensitisation among a large groupof healthcare workers, study the occupa-tional and non-occupational factors asso-ciated with latex allergy, and characteriselatex exposure in air and by gloves.Methods-All 2062 employees of a generalhospital in Hamilton, Ontario, Canadawho regularly used latex gloves wereinvited to participate in a cross sectionalsurvey, representing the baseline phase ofa prospective cohort morbidity study.Attempts were made to recruit employeeswho were diagnosed with latex allergybefore the survey. Glove extracts wereassayed for antigenic protein, and areaand personal air samples were obtainedon two occasions (summer and winter) toestimate exposure to airborne latex pro-tein. A questionnaire on medical andoccupational information was adminis-tered by an interviewer. Skin prick testswere performed with latex reagents, threecommon inhalants, and six foods.Results-The mean (SD) latex proteinconcentrations were 324 (227) yg/g inpowdered surgical gloves and 198(104) ug/g in powdered examinationgloves. Personal latex aeroallergen con-centrations ranged from 5 to 616 nglm3.There was a total of 1351 (66%) partici-pants. The prevalence of positive latexskin tests was 12 1% (95% confidenceinterval (95% CI) 10-3% to 13.9%). Thisprevalence did not vary by sex, age, hos-pital, or smoking status but subjects whowere latex positive were significantlymore likely to be atopic (P < 0-01).Participants who were latex positive werealso significantly more likely to have posi-tive skin tests to one or more foods(Mantel-Haenszel odds ratio (OR)adjusted for atopy 12-1, 95% CI 7-6 to 19-6,P < 10-9). Work related symptoms weremore often reported among latex positivepeople, and included hives (OR 6-3, 95%CI 3-2 to 12.5), eye symptoms (OR 1-9,95% CI 1-2 to 2.8), and wheezy orwhistling chest (OR 4 7, 95% CI 2-8 to7.9). The prevalence of latex sensitivitywas highest among laboratory workers(16.9%), and nurses and physicians(13-3%). When the glove consumption perhealthcare worker for each departmentwas grouped into tertiles, the prevalenceof latex skin test positivity was greater inthe higher tertiles of glove use for sterile

(surgical) gloves (P < 0.005) but not forexamination gloves.Conclusions-In this large, cross sec-tional study of healthcare workers, theprevalence of latex sensitisation was12-1% (9-5% among all those eligible), andthere were significant associations withatopy, positive skin tests to certain foods,work related symptoms, and departmen-tal use of gloves per healthcare worker.This cohort is being followed up prospec-tively and will be retested to determinethe incidence of development oflatex sen-sitivity.

(Occup Environ Med 1997;54:335-342)

Keywords: latex; allergy; healthcare workers

Allergy to natural rubber latex has become animportant occupational health concern inrecent years, particularly among healthcareworkers. 1-5 The main source of workplaceexposure is use of powdered latex gloves byhealthcare workers. Workers involved in glovemanufacturing may also be affected.6 Type I(IgE mediated) latex allergy includes urticaria,angioedema, rhinitis, conjunctivitis, bron-chospasm, and anaphylaxis.

Surveys of healthcare workers have showedthat the prevalence of sensitisation to naturalrubber latex ranged from 2-9% in Finland7 to4-7% in Belgium8 among hospital employeesas a group, and from 7% among operatingroom staff in Finland7 to 9%-10% amongoperating room nurses in France9, and sur-geons, anaesthesiologists, and radiologists inCanada.10 Vandenplas et a18 documented that2 5% of healthcare workers had occupationalasthma induced by latex confirmed with spe-cific inhalation challenge. Factors that havebeen associated with latex allergy in previousstudies of healthcare workers include atopy,skin rash (mainly hand dermatitis), and occu-pation. Relations with measures of cumulativeexposure or hours of glove use have not beenconvincing.7 811 A recent Finnish study, how-ever, found skin symptoms among hospitalworkers associated with hours of daily gloveuse but tests for latex allergy were not per-formed.'2

It is postulated that exposure to medicalgloves high in latex protein has sensitizedmany healthcare workers. Sensitisation ofthese workers may involve high costs, both interms of day to day risks at work, as well aspotentially fatal anaphylactic shock. Disability

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from latex sensitivity is an increasing problemrequiring substitution of latex products, per-sonnel reassignments, and workers' compen-sation claims. Turjanmaa and Lahti"3 foundthat people already sensitised to latex reactedless to an extract taken from a low proteinglove than to an extract from a regular glove.Also, Vandenplas et al 4 suggested that gloveswith a lower protein content could be useful inreducing the risk of asthmatic reactions in sub-jects with latex induced asthma. It is notknown, however, if the use of low proteingloves will reduce the incidence of latex sensiti-sation. The need for such a study has beennoted.'i"s

During 1992 and 1993, many healthcareworkers at a hospital (with two sites) inHamilton, Ontario, Canada, developed aller-gic symptoms that were associated with expo-sure to latex. This provided an opportunity toundertake the current investigation to test thehypothesis that high protein concentrations inlatex gloves are related to the incidence of sen-sitisation. The objectives of this study were toexamine (a) the prevalence of latex allergy in agroup of healthcare workers, (b) the factorsassociated with latex allergy at baseline, (c) theincidence in the prospective phase, at whichpeople within this group become newly sensi-tised to latex, and (d) the association, if any,between the rate of sensitisation and the pro-tein content of the latex gloves worn or air-borne exposure.

Overall designThe study design had two main components.The first phase was a cross sectional investiga-tion in which healthcare workers who usedlatex gloves at the two sites of the Hamiltonhospital were screened to find the baselineprevalence of sensitivity to latex. The secondcomponent involved prospectively followingup the cohort, and retesting after one year toidentify changes in latex sensitivity and newlysensitised people (objectives c and d). At onesite, most departments continued to use thesame powdered gloves as in the past, whereasat the other site, powderless low protein gloveswere introduced. In this report, we describethe prevalence findings at baseline among theparticipants.

MethodsELGIBLE POPULATIONAll 2062 employees at both sites who usedlatex gloves on a regular basis (at least once ortwice a week) were invited to participate in thebaseline screening. The assessment includedadministration of a questionnaire, latex skintesting, and obtaining serum samples. Theresults of in vitro assays of serum samples forIgE antibody to latex will be reported sepa-rately. Informed signed consent was obtainedfrom all participants and the study protocolreceived approval from the review board of thehospital.To promote participation, advanced public-

ity included meetings with union leaders;

notice in the hospital newsletters; and presen-tations to large hospital groups. Testing andinterviewing occurred over four weeks. Thoseemployees who had been documented as hav-ing latex allergy during the two years beforethe study were encouraged to participate.These employees were also identified by affir-mative answers from the questionnaire to thequestions "Have you ever been told by a doctorthat you have an allergy to latex?" and "Wasthe doctor's statement based on a skin pricktest for latex allergy?" Those employees whocompleted a questionnaire and answered affir-matively were included in the study analysisand were considered to be latex positive. (Infact, all those who were retested by an allergistwere clearly positive to the latex skin pricktest.) All 76 people known to be sensitised(whether participants in the questionnaire ornot) are included in the overall estimate ofprevalence.

QUESTIONNAIREThe questionnaire was given by four trainedinterviewers. It obtained information on occu-pational history including job title, depart-ment, number of pairs of gloves, and numberof hours of gloves used (over the three daysbefore interview), types of glove worn duringpast year, glove brands, exposure to otherlatex items (household cleaning gloves, bal-loons, diaphragm, latex condoms), number oftimes a day that hands were washed, andexposure to chemical irritants at work. We alsoasked about smoking, medical history, andallergies. Questions about symptoms wereadapted from a questionnaire previously usedin health hazard evaluations in Ontario and atthe National Institute for Occupational Safetyand Health (NIOSH).'617

DEFINITIONS OF SYMPTOMSThe questionnaire asked whether the follow-ing symptoms were present "on a persistentbasis". Skin rash (dermatitis or hives) was con-sidered to be present if reported a few times amonth or all the time. Eye symptoms werepresent if two or more symptoms (burning,running, or itching) were reported and the fre-quency was at least a few days a week. Mouthirritation symptoms were present if one ormore symptoms (itchy throat, tongue, or roofof the mouth) were reported at least a few daysa week. Nasal symptoms were considered tobe present if two or more symptoms (sneezing,runny, stuffy, or itchy nose) were reported atleast a few days a week. A persistent cough waspresent if the frequency was at least a few daysa week. Wheezy or whistling chest was presentif it occurred "occasionally even when youdon't have a cold" or "most days or nights".Each of these symptoms (except for rash) wasconsidered to be work related if the symptommet the above conditions and if it occurred notat all or less often on days away from work orwhen on holiday compared with workdays. Itwas not considered realistic that a rash wouldnecessarily subside over a weekend.Associations of positive skin prick test to latexwith symptoms were adjusted for atopy.

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SKIN TEST DEFINITIONSA positive skin prick test was defined as awheal diameter of at least 4 mm. Atopy wasdefined as two or more positive skin prick teststo common inhalant aeroallergens (ragweed,dust mite, or timothy grass). A positive latexskin prick test was defined as a positive skintest to any of the latex reagents tested.

LATEX SKIN TEST REAGENTSSkin testing was done with dilutions of com-mercially available ammoniated latex extracts(Bencard Laboratory, Mississauga, Ontario,Canada). Bencard latex extracts were analysedin vitro by the western blotting technique andcontained all relevant proteins.'8 Skin test dilu-tions to 1: 10, 1 :100, 1: 1000, 1:10 000,1:100 000, and 1:1 000 000 of the stock latexextracts were prepared with saline diluent. Inpatients with histories suggestive of latexallergy (identified by questionnaire), skin testswere carried out beginning with the lowestdilution and progressing through increasingconcentrations until a definite positive skintest was obtained. In patients with no symp-toms suggestive of latex allergy, skin tests werecarried out with all latex dilutions at one time.

Another reagent containing latex proteinswas extracted from non-compounded ammo-niated latex. Three lots of ammoniated latex(Guthrie Latex) were mixed together andpoured on to a large glass plate. The latex wasair dried overnight to produce a thin sheet.The resulting latex film was cut into smallpieces, placed in polyethylene bottles, andextracted with continuous agitation in 0-05 Mcarbonate buffer pH 9-6, overnight at 370C.The extract was collected, centrifuged(2000 g), and dialysed (MWCO 1000) againstH2O for two days at 4VC and lyophilised. Theresidue was reconstituted to 1 mg/ml in sterile0 05 M carbonate buffer (pH 9 6) containing30% glycerol.

Glove extracts used for skin testing wereprepared as reported previously.'9 Two gramsof the palmar surface of latex rubber gloves(Suretex (Page Products, Burlington,Ontario); Microtouch (Johnson and Johnson,Arlington, Texas); No-Powder (AnsellMedical, Eatontown, New Jersey);Neutraderm (Aladan Corporation, Dothan,Alabama)) were cut into 2 cm squares andsubmerged in 10 ml saline, agitated for 30 sec-onds to ensure all parts were wetted, and leftfor 15 minutes. The latex extracts were pre-pared in polypropylene tubes and containers.The final latex glove extracts were refrigeratedand stored in 5 ml aliquots. The solution waslabelled with date, glove brand, and glove lotnumber. The extract was assayed for antigenicprotein with an indirect enzyme linkedimmunosorbent assay (ELISA) technique.20

FOOD AND INHALANT SKIN TEST EXTRACTS

Commercially available food and inhalantextracts were used for skin testing. Foodextracts (Bencard Laboratory, Mississauga,Ontario) included avocado, banana, kiwi,potato (all 1:10 dilution), and chestnut andcow's milk (1:20 dilution). Inhalant extracts

included ragweed, Timothy grass, dust mite(Bencard Laboratory, Mississauga, Ontario,Canada). Histamine (1:1000) (BencardLaboratory), and physiological saline served aspositive and negative controls, respectively.

SKIN TEST METHODSkin prick tests were performed by trainedregistered nurses. Both forearms were wipedclean with alcohol. Skin test sites were clearlymarked, a drop of extract was placed on theskin, and this was pricked with commerciallyavailable skin test lancets (Hollister StierLaboratory, Etobicoke, Ontario, Canada).Skin tests were read at 15 minutes; all positivetests were measured. All positive skin testwheal and flare responses were outlined withblack pen and transferred to paper with trans-parent tape. Those tests that were < 3 mmwere considered negative. Forty seven subjectswith latex minus saline differences of 3 mmwere considered equivocal and referred to anallergist for follow up tests; 27 of these wereseen and tested and the allergist's skin testdiagnosis was used in the analysis. Subjectswith 3 mm wheal responses who did notattend were considered negative.

OUTCOMES EXAMINED AT BASELINEWe declared in advance our interest in exam-ining the prevalence of positive skin prick teststo latex, occupational and non-occupationalfactors that might predict latex skin prick teststatus, and whether work related symptomswere associated with latex skin prick test sta-tus.

EXPOSURE ASSESSMENTDirect exposureTo provide estimates of the range of airbornelatex concentrations, a few area and personalair samples were obtained in both hospitals tocharacterise areas of frequent and no or lowglove use. These were conducted on two occa-sions (winter and summer) to reflect differentventilation conditions. In this report wedescribe the results from areas in which pow-dered (moderate protein) gloves were used,which reflected exposures during the exposureinduction period before this prevalence survey.The results of sampling at places where pow-derless low protein gloves were used will becommunicated in the report of the follow upstudy.

Air sampling methodAir samples assayed for airborne latex proteinwere collected by drawing air through teflon(polytetrafluoroethylene) filters at a flow rateof 3-5 or 4-0 1/min for personal samples and180 1/min for area samples.

Analytical methodThe immunoassay for latex aeroallergens hasbeen previously described.2' 22 Briefly, the latexallergens were extracted with buffer and mea-sured by inhibition immunoassay with a con-centrated extract from latex gloves adsorbedon to plastic microtitre plates and IgE antibod-ies specific to latex pooled from five latex sen-

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Table 1 Results of air samplingfor latex: Hamilton Hospitals Latex Study, Ontario,1994

Personal samples (nglm3) Area samples (ng/m3)

Hospital (location) Summer 1994 Winter 1995 Summer 1994 Winter 1995

Wards 5 40 4 209 87 6 24

19 38837 61683

Operating rooms 7 133 5 297 19 33

Table 2 Comparison ofstudy participants with those eligible: Hamilton Hospitals LatexStudy, Ontario, 1994

Participants Eligible(n = 1351) (n = 2062)n (%a) n (%o)

Year of birth (known for 1305):< 1940 80 (6-1) 128 (6 2)1940-49 284 (21-8) 412 (20-0)1950-59 407 (31-2) 657 (31-9)> 1960 534 (40 9) 865 (41-9)

Sex (F, n (%)) 1208 (91 1) 1916 (92 9)Hospital site (known for 1296) (n (%)):

General 753 (58-1) 1212 (58 8)Henderson 543 (41-9) 850 (41-2)

sitive people. The results were expressed aslatex allergenic protein/M3 air. The lower ana-lytical limit of detection of this method wasabout 2 ng or 40 ng/ml.

Indirect exposure measuresIt was not feasible to sample all wards or areas.The following extra variables were declared inadvance to be exposure metrics of interest toexplore as possible predictors of a positive skinprick test to latex: hospital; departmental useof gloves (obtained from hospital purchasingrecords over the previous year); job title; num-ber of gloves a day averaged over the threedays before the interview; number of hours aday wearing gloves; and exposure to chemicalirritants at work.

STATISTICAL ANALYSESWe compared categorical variables with x2tests or Fisher's exact test (two tailed) andcontinuous variables with t tests as appropri-ate. The association of work related symptoms

Table 3 Characteristics ofparticipants positive for skin prick test (SPT) to latex:Hamilton Hospitals Latex Study, Ontario, 1994

Characteristic (n)

All (n = 1326)Age group:

< 30 (264)30-39 (447)40-49 (358)> 50 (211)Total known (1280)

Sex:(F, 1208)(M, 108)

Hospital site (known for 1296):General (753)Henderson (543)

Atopy:Yes (138)No (1187)

Smoking:Ever smoked:

Yes (639)No (687)

Smoking status:Current (269)Ex (370)Never (687)

Latex SPTpositiven (% positive)

160 (12-1)

23 (8 7)53 (11 9)47 (13-1)23 (10-9)146 (11-4)

148 (12-3)12 (11 1)

91 (12-1)66 (12-2)

61 (44-2)99 (8-3)

72 (11-3)88 (12-8)

26 (9 7)46 (12-4)88 (12-8)

P value

> 0-3

NS

NS

< 0-01

NS

NS

among skin prick test positive and negativesubjects was compared after adjustment foratopy with Mantel-Haenszel odds ratios(ORs). In these analyses, the probability ofhomogeneity across strata of the variable,atopy, was calculated as an indicator of possibleinteraction. The ORs for chest symptoms werealso adjusted for smoking. For the compar-isons of glove use between groups, we used theMann-Whitney test. We used the SAS (Cary,NC), SPSS (Chicago, Ill), Epistat (EpistatServices, Richardson, Texas), and SYSTAT(Chicago, Ill) statistical programs. A P valueof < 0 05 was considered to be significant.

ResultsEXPOSUREThe powdered surgical gloves used were foundto have mean (SD) latex protein concentra-tions of 324 (227) /g/g (for 45 lots) and thepowdered examination gloves had 198(104) yg/g (for six lots) with the ELISAmethod. The protein concentrations weremeasured for representative lot numbers usedfrom March to September 1994. Table 1 dis-plays the results of personal and area samplingfor airborne latex during use of regular pow-dered gloves. All samples where gloves werenot in use showed non-detectable concentra-tions. The personal exposures ranged from5-83 ng/m3 in the summer, and 40 to616 ng/m3 in the winter. The number of pairsof powdered gloves reported as used on thedays of sampling ranged from three to 14(median six). When we examined the correla-tion between the number of pairs of gloves,and the personal latex exposures of employeessampled on the wards, there was no positivecorrelation overall (r= -0*26, n = 9).However, when analysed according to season,there was a moderate negative correlation inthe summer, when exposures were lower (r =- 0-6, n = 5), but a weak positive correlationin the winter, when exposures were muchhigher (r = 0 3, n = 4). After excluding thehighest outlying value of 616 ng/m3, there was amoderately strong positive correlation in win-ter (r = 0-6, n = 3).

PARTICIPANTSThe total number of participants in the base-line survey was 1351, representing a participa-tion rate of 66%. The participants included 40(53%) of the 76 employees identified as sensi-tive to latex before the survey. Participationwas voluntary; thus, it was not possible to con-tact non-participants for reasons for not par-ticipating. However, compared with all thoseeligible to participate, the participants wereidentical for age, sex, and hospital (table 2).

PREVALENCE OF POSITIVE SKIN PRICK TESTS TOLATEXAmong the 1326 participants with skin tests,there were 160 (12 1%) who were positive tolatex (95% confidence interval (95% CI)10-3% to 13-9%). Including all those previ-ously known to be latex positive, an estimateof the minimum prevalence in the entire eligible

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Table 4 Frequency ofpositive skin tests to latex reagents:Hamilton Hospitals Latex Study, Ontario, 1994

Skin prick testReagent positive (n)

Bencard full (7 5 mg/ml) 56Bencard 1 :10 37Bencard 1:100 10Bencard 1:1 000 2Bencard 1:10 000 0Bencard 1:100 000 0Bencard 1:1 000 000 1Ammoniated latex (1 mg/ml) 37

population was 9-5% (95% CI 8-2% to10-8%). All subsequent analyses refer to thesurvey participants only. Table 3 shows thedemographic and background characteristicsof the people positive and negative for skinprick tests to latex. The prevalence of positivitydid not vary by sex, hospital, or smoking.There was also no significant difference in age

distribution, although the prevalence of posi-

tivity was somewhat lower in the youngestgroup. Subjects who were sensitive to latexwere significantly more likely to be atopic thanthose who were negative (table 3); atopy wasconsidered in subsequent analyses. Overall,10-4% of participants were atopic. Table 4shows the relative frequency with which thelatex skin test reagents elicited positiveresponses.We examined other potential sources of

exposure to latex. The prevalence of reportedpast surgical or radiological procedures, or

adverse reactions during such procedures didnot differ between those who were positiveand those who were negative for skin pricktests to latex. We also asked about exposure tocondoms, balloons, and household cleaninggloves in the past month; however, fewer than20% of participants responded to this ques-tion. Of those responding, those who were

latex positive were somewhat less likely toreport exposure to balloons (31-8% v 46-8%)and household gloves (34-6 v 46-9%) but were

as likely to report use of latex condoms in thepast month (9-5% v 9-6%).

ASSOCIATION OF FOOD ALLERGY AND LATEXSKIN PRICK TEST STATUSParticipants who were positive for skin pricktests to latex were much more likely to havepositive skin tests to one or more of the testedfoods (71 (44-4%) of 160) than those whowere skin test negative (49 (4-2%) of 1166, P <0-001); this association was found among peo-ple with atopy (OR 10.5) and without (OR12-9, Mantel-Haenszel OR adjusted for atopy12-2, 95% CI 7.6 to 19-6, P < 10-9). Thedetailed findings for specific foods will bereported separately.

SYMPTOMS ACCORDING TO LATEX SKIN PRICKTEST STATUSTable 5 shows the association of work relatedsymptoms with skin prick tests to latex. Allsymptoms were more prevalent among peoplepositive than negative for skin prick tests tolatex, with little change in relative risk afteradjustment for atopy. The associations were

strongest for hives and for wheezy or whistlingchest, and were significant for these symptomsas well as for itchy skin, skin rash, and eye

symptoms. For cough and mouth irritation,the associations were also positive but the 95%CIs for the ORs included unity. The ORs forrespiratory conditions (cough, and wheezy or

whistling chest) did not change when theywere further adjusted for smoking (table 5). Ingeneral, the associations with positive skinprick tests to latex were stronger among peo-ple without than with atopy for almost allsymptoms (table 5). For nasal symptoms therewas a significant interaction with atopy.

Table 5 Prevalence of work related symptoms according to latex skin test status: Hamilton Hospitals Latex Study, Ontario, 1994

Symptom prevalence (%) WR symptoms among X2 forCrude Adj OR* homogeneity

Symptom All WR Latex SPT+ SPT- OR (95% CI) P value (P value)

Skin rash 11-8 - 18 8 10-8 1-9 (122-29) 2-0 (1-3 to 3 2) 0 002 > 0 3Hives 4-1 3-5 113 2-5 5-0 6-3t (3-2 to 12-5) < 0 001

Atopy x > 0 1No atopy 4-6

Itchy skin 12-1 10-8 20-0 9-5 2-4 2-5 (1-6 to 3-8) < 0 001Atopy 1-5 > 0 2No atopy 2-9

Eyesymptoms 18 5 15-2 22-5 14 2 1-8 1-9 (1-2to 2-8) 0-004Atopy 1-2 > 0-25No atopy 2-2

Mouth irritation 6-7 5-2 8-1 4 8 1-8 1-7 (0 9 to 3 2) 0-08 > 0.15Atopy 0 7No atopy 23

Nasal symptoms 14-5 8-8 15-6 7-8 2-2Atopy 0 7 (0-2 to 2-1) < 0 05tNo atopy 3-1 (1-8 to 5-3)

Cough 8-0 4-9 7 5 4-6 1 7 1.5 (0-8 to 3 0) 0 23 > 0 70Atopy 1-3No atopy 1-6

1-5 (0-7 to 3 0)§Wheezy or 16-5 5-4 14 4 4 1 3-9 4-7 (2-8 to 7 9) < 0.001 > 0-60whistling chest

Atopy 3-3No atopy 5.0

4.7 (2-8 to 8 0)§*Mantel-Haenszel OR for association of symptoms and latex SPT status, adjusted for atopy status.tLogistic regression model; 5-0 (95% CI 2-5 to 10-1) due to correction for cell containing zero.

*X2 for homogeneity significant (interaction between atopic status and latex SPT status).§Mantel-Haenszel OR adjusted for atopy and smoking status.

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Table 6 Comparison of various exposure measures between latex skin prick test (SPT) +and SPT- participants: Hamilton Hospitals Latex Study, Ontario, 1994

Exposure measure Latex SPT+ latex SPT- P value*

Job title (%):Lab workers (65) 16-9 83 1Nurses and physicians (788) 13-3 86 1 0.15Housekeepers (78) 11-5 88-5Therapists and technicians (145) 7-6 92-4Others (231) 9-5 90 5

Gloves per day (mean (SD) over past Mann-3 days): Whitney

Total 9-4 (12 3) 9-5 (12 5) > 0 7Latex 5 4 (10-1) 6-6 (11 6) 004Vinyl 4-0 (8-7) 2-9 (7 1) 0 03

Hand contact (% > 1/week) with:Formaldehyde 3-1 3 1 > 0 9Glutaraldehyde 1-3 2 3 > 0-3Bleaches 11-3 16 6 0-08Cleaners 22-5 22-4 > 0 9

*%2 unless indicated.

EXPOSURE FACTORS ACCORDING TO LATEXSKIN PRICK TEST STATUSIrritantsThose who were latex positive were somewhatless likely to have had hand contact withbleaches or glutaraldehyde and were as likelyto have been exposed to formaldehyde or handcontact with cleaners (table 6). There was noassociation of skin prick test positivity with thenumber of times a day that the participantswashed their hands at work or use of handcleaners before donning gloves.

Job titleThe prevalence of latex positivity was highestamong nurses, physicians, and laboratoryworkers and intermediate among housekeep-ers; however, the differences between job cate-gories were not significant (table 6).

USE OF GLOVES BY HEALTHCARE WORKERSOver the three days before the survey, therewere no differences between those who wereand were not allergic to latex in the total num-ber of pairs of gloves used each day (table 6)or hours that latex gloves were worn each day(data not shown). However, those who werelatex positive reported using fewer latex andmore vinyl gloves a day than those who werenot (table 6).

Glove consumption by departmentsFor use of sterile gloves and bulk (examina-tion) gloves, the consumption per healthcareworker by department was ranked andgrouped into tertiles. For each department,the proportion of participants who were posi-tive for skin prick tests to latex was found andcategorised into whether this prevalence forpositivity was higher or lower than the overallprevalence. For use of sterile gloves, there was

Table 7 Prevalence ofpositive skin prick tests (SPT) to latex and departmental gloveconsumption

Departments with SPTLatex glove consumption! prevalence exceedinghealthcare worker overall average (n) X2 test

Sterile gloves:Lowest tertile departments 1 of 10 15 8Medium fertile departments 9 of 10 (2 dfHighest tertile departments 8 of 10 P < 0-005)

Bulk (examination) gloves:Lowest tertile departments 6 of 13 1-44Medium tertile departments 5 of 13 (2 df;Highest fertile departments 8 of 13 P > 0 20)

evidence that in departments with high gloveconsumption per healthcare worker there wasa high prevalence of positive skin prick tests tolatex (table 7). However, this relation couldnot be found for examination gloves.

DiscussionIn this study, which is one of the largest crosssectional surveys undertaken for latex sensitiv-ity among healthcare workers, the estimate ofthe prevalence of latex positivity among partic-ipants was 12-1% (and an estimate of the min-imum prevalence in the total eligiblepopulation was 9 5%), comparable with theupper range of previous estimates.9 10 Becausewe used a relatively conservative definition ofpositive latex sensitivity (at least 4 mm diame-ter wheal), it is unlikely that the prevalence hasbeen greatly overestimated. For comparison,the prevalence of latex allergy in the generalpopulation is thought to be less than 1%.7

Although only a portion of those withimmunological sensitisation were symptomaticor were likely to have had occupationalasthma, this prevalence of allergic sensitisationconstitutes a high "attack rate" or proportionaffected. Our finding of the strong associationwith atopy is consistent with previous find-ings.78 23 At least 40% of participants withpositive skin prick tests to latex were asympto-matic; the clinical significance of asympto-matic positivity is not known but this mayidentify a group at risk of becoming sympto-matic in the future. Prospective follow up willbe required to answer this question.

There was little evidence that those whowere latex positive had more frequent expo-sure to other sources of latex exposure suchas past operations, condoms, or householdgloves. However, these findings should beinterpreted with caution due to the small num-bers responding and because this reflects onlythe month before the survey. It is possible thatrespondents modified these practices afterbecoming sensitised.The most likely source of latex exposure

was from the use of gloves at work. The airsampling results documented exposure tolatex during use of gloves with no exposuredetectable in the background areas wheregloves were not used. The concentrations werehigher in the winter and were comparable withthe range of 39 to 311 ng/m3 documented in alaboratory setting22 and 8 ng/m3 to 974 ng/m3in the breathing zone of healthcare workerswho used powdered gloves.' We found lim-ited evidence of a positive correlation betweenthe number of pairs of powdered gloves usedand personal latex exposure during the winter,when there was decreased circulation of freshair and exposure was higher. Heilman et al24recently found a similar correlation of latexaeroallergen concentrations with the numberof latex gloves containing high concentrationsof allergen (r = 0 66), based on many moreobservations.A possible mechanism leading to sensitisa-

tion other than through inhalation couldinvolve exposure to irritants-for example,

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Latex allergy: epidemiological study of 1351 hospital workers

bleaches and cleaners-causing impairment ofthe integrity of the skin barrier, allowing entryof latex antigen. For example, Turjanmaa7found skin irritation from gloves and handeczema to be more frequent among those posi-tive to skin tests, as did Charous et al.1I Oursubjects positive for skin prick tests to latexdid not report more frequent hand contact toirritants such as bleach and cleaners but didreport a greater prevalence of skin rashes. It ispossible that this may reflect that those whowere sensitised (and previously had contact)were now avoiding these materials.

REACTIONS TO FOODSOur finding of a very strong association ofreaction to foods such as chestnut, banana,and kiwi, with latex positivity confirms previ-ous reports by us25 and by others.26

SYMPTOMSThe prevalence of most work related symp-toms was found to be relatively low (usuallybelow 10%). However, all symptoms werepositively associated with being latex posi-tive-that is, they were reported more often bythose who were sensitised to latex. This associ-ation was strongest for hives (as opposed tosymptoms of the eye, mouth, nose, and chest),which more specifically indicates a conditionrelated to latex mediated through IgE. Theassociation of symptoms and latex skin pricktest status was generally stronger among peo-ple without rather than with atopy. The expla-nation for this is not known but it may be thatpeople with atopy have higher backgroundsymptoms or react to non-specific triggersmore often than those without, and therefore, itmay be more difficult to detect a furtherincrease after sensitisation to latex. However,in our data, symptoms were remarkably simi-lar among those with and without atopy (datanot shown). Alternatively, people withoutatopy may not respond to non-specific irritantsin the workplace but may develop symptomswhen sensitised and then exposed.

For nasal symptoms, there was a significantinteraction between results of skin prick teststo latex and atopy, with the direction of theassociation differing according to atopic sta-tus. For respiratory symptoms, cough was notsignificantly associated with skin prick testresults but wheezy or whistling chest was. Thissymptom is more closely identified with bron-chospasm but as the final clinical diagnosis isnot known in all cases, it is not possible tospeculate about the interpretation.

EXPOSURE VARIABLESPrevious studies have shown associationsbetween the prevalence of latex sensitivity andjob title, but few have been able to show rela-tions with other factors related to exposure.Kujala and Reijula"2 found that in a logisticregression analysis, skin symptoms among 522hospital workers in Finland were associatedwith hours of daily use of gloves and workexperience (decreasing with years worked).Interestingly, there was no associationbetween glove type (latex v vinyl) and skin

symptoms when other factors were taken intoaccount in the model, but latex sensitivity wasnot ascertained.We found that the prevalence of positive

skin prick tests to latex was greater (althoughnot significantly so) among physicians, nurses,and laboratory workers. The prevalence wasintermediate among housekeepers, consistentwith our recent findings at a Toronto hospi-tal.23 We failed to find an association with thenumber of hours that gloves were worn eachday, although those who were latex positivereported using fewer latex gloves a day.However, because the participants were askedabout the three days before the survey, thismay not reflect past use of gloves in the rele-vant period when sensitisation occurred. Infact, some participants who were sensitisedmay have already modified their practice toreduce their use of latex gloves.The positive association that we found with

glove use per healthcare worker is interestingand needs to be confirmed elsewhere. Becausethis measure represents a measure of exposurethrough gloves by department over the pastyear (and may reflect use of gloves in earlierperiods as well), it may relate more meaning-fully to the period of sensitisation. This rela-tion was found for sterile but not for bulkgloves. Whether this is due to a differencebetween sterile and bulk gloves (the meanlatex protein concentration was 50% higher inthe sterile gloves), to a difference in the activi-ties conducted with sterile gloves, to misclassi-fication of use of bulk gloves, or to otherfactors is not clear.

LIMITATIONSThis study was limited in part by its cross sec-tional design. Subjects who may have devel-oped latex sensitivity may have left theworkforce before the study, leading to anunderestimation of the prevalence of latex sen-sitivity. This was considered in part by offeringthose previously diagnosed an opportunity toparticipate, and successfully recruiting a highproportion of them. Also, we included allthose previously diagnosed in the estimate ofthe minimum prevalence. Selection bias wasalso possible if non-participants differed some-how from participants or if those who thoughtthat they were symptomatic or sensitised tolatex were more likely to participate, whichcould result in an overestimation of risk esti-mates. Although we were unable to interviewnon-participants, table 2 suggests that thegroups were essentially identical in several keycharacteristics. Finally, it should be acknowl-edged that no gold standard or controlledchallenge was used in this study for confirmingclinical sensitivity.

SUMMARYThe best estimate for the prevalence of posi-tive skin prick tests to latex among participantsin this large cross sectional study was about12%. Strong associations were found betweenlatex positivity and atopy, positive skin tests tofoods, and work related symptoms. Occu-pational risk factors of positive skin prick tests

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Liss, Sussman, Deal, Brown, Cividino, Siu, et al

to latex included job title and an interestingassociation with use of sterile gloves perhealthcare worker within departments. Theworkers in this study will be followed upprospectively and retested to determine theincidence of development of sensitivity tolatex.

This work was supported in part by Aladan Corporation(Dothan, Alabama), Ansell Medical (Eatontown, New Jersey),and Regent Hospital Products (Greenville, South Carolina).The cooperation of these companies and Johnson and Johnson(Arlington, Texas), and Page Products (Burlington, Ontario) isappreciated.We thank the participants themselves and the hospital

administration. Marlene Vaz assisted with preparation of thetables.

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hospital workers.Latex allergy: epidemiological study of 1351

P Lebert, P Keith, S Wasserman and K TurjanmaaHolness,Beezhold, G Smith, M C Swanson, J Yunginger, A Douglas, D L

G M Liss, G L Sussman, K Deal, S Brown, M Cividino, S Siu, D H

doi: 10.1136/oem.54.5.3351997 54: 335-342 Occup Environ Med 

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