Occupational and Environmental Medicine 1997;54:873-879

Airway symptoms and lung function in pipelayersexposed to thermal degradation products fromMDI-based polyurethane

K Jakobsson, K Kronholm-Diab, L Rylander, L Hagmar

Department ofOccupational andEnvironmentalMedicine, UniversityHospital,S-221 85 Lund, SwedenK JakobssonK Kronholm-DiabL RylanderL Hagmar

Correspondence to:Dr Kristina Jakobsson,Department of Occupationaland EnvironmentalMedicine, UniversityHospital, S-221 85 Lund,Sweden.

Accepted 5 June 1997

AbstractObjectives-To study the prevalence ofsymptoms from the eyes and the upperand lower respiratory tract, lung function,and immunological sensitisation towardsisocyanates in pipelayers exposed to ther-mal degradation products from methylenediphenyl diisocyanate (MDI)-based poly-urethane (PUR).Material and methods-50 presently ac-tive and 113 formerly active pipelayerswere examined. Also, 65 unexposed work-ers were investigated for comparison. Theone year prevalence of symptoms andsmoking history (questionnaire data),lung function (vital capacity (VC) andforced expiratory volume in one second(FEVy), and atopy (positive skin prick teststowards standard allergens) were assessedamong pipelayers and controls. For thepipelayers, the presence of work relatedsymptoms and estimates of isocyanateand welding exposure were obtained froman interview. Skin prick tests towards spe-cific isocyanate antigens and determina-tions of IgE-MDI and IgG-MDI in serumwere also performed.Results-The prevalence of episodes(more than once a month) ofirritative eyesymptoms, congestion of the nose, andsoreness or dryness in the throat wasmuch higher among the PUR pipelayersthan among the controls. Most of thepipelayers with symptoms reported thatthese had started and occurred in relationto the PUR welding tasks. Presently activepipelayers with recent high PUR exposureshowed a significant reduction of FEV,compared with the controls. The esti-mated reduction, adjusted for smoking,was -0.3 1 (P=0.04). There was no con-founding effect of ordinary welding. Noneof the pipelayers showed positive skinprick reactions against the specific isocy-anate antigens used, or positive IgE-MDI,and only two had increased IgG-MDI.Conclusions-The findings indicate thatexposure to thermal degradation productsfrom MDI-based polyurethane has ad-verse effects on the mucous membranesand airways.

(Occup Environ Med 1997;54:873-879)

Keywords: methylene diphenyl diisocyanate; respiratorydisease; construction industry

Isocyanates are agents responsible for a sub-stantial proportion of occupational asthma.' Inindustrial handling, methylene diphenyl diiso-cyanate (MDI) has been considered to have alow potential in inducing respiratory diseasecompared with other isocyanates, because of itslow vapour pressure. However, especially inconnection with spraying or heating, MDI hasbeen associated with asthmatic, as well assystemic reactions.2 The pathogenetic mecha-nisms are still controversial; irritant, immuno-logical and pharmacological mechanisms havebeen suggested, and may well coexist. More-over, irritative conjunctival and upper airwaysymptoms may also be prevalent after exposureto MDI,3 6 but have arroused less interest.

In the present study we examined pipelayerswho had been welding district heating pipesinsulated with polyurethane (PUR) foam. Thisfoam is a complicated structure formed bypolymerisation of a mixture of reagents mainlycontaining 4,4'-MDI, 2,2'-MDI, 2,4'-MDI,and polyethers with one or two hydroxylgroups. If the foam is not thoroughly removedfrom the mild steel pipe before welding, thepipelayers are exposed not only to the weldingfumes but also to thermal degradation prod-ucts from the foam. These products includenumerous different isocyanates, amino-isocyanates and amine compounds.7 Work-place monitoring with a filtertape instrumenthas indicated considerable exposure (MDalene, personal communication). A biomar-ker, 4,4-methylenedianiline, has been used toassess isocyanate exposure among these pipe-layers.8 In the present study the aims were toinvestigate the prevalence of symptoms fromthe eyes and the upper and lower respiratorytract, and lung function. Further, immunologi-cal tests were performed to detect possible sen-sitisation.

Material and methodsPIPEILAYERS: STUDY GROUP AND EXPOSUREThirty one companies engaged in PUR pipe-laying in the south of Sweden were identifiedfrom telephone directories and from suppliersof pipes. From all but one, we obtained lists ofpresent and former employees who had everparticipated for at least four weeks in suchwork. Information on the study was sent toeach subject, together with a short enquiry onwork related symptoms, duration of work withPUR, and smoking. The entry criteria weremet by 228 men, of whom 163 (71%) partici-pated in the total examination; for the remain-

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Table 1 Age, smoking habits, and exposure among pipelayers and controls

PUR pipelayers

Presendy active Formerly active Controls

Subjects (n) 50 113 65Age* 38 (25, 53) 49 (35, 61) 41 (22, 59)Smoking habits:

Lifelong non-smoker (n (%)) 18 (36) 25 (22) 34 (52)Ex-smoker (n (%)) 19 (38) 59 (52)

Pack-years* 14 (2,27) 14 (2, 33)Age at start of smoking* 16 (15, 21) 17 (14, 20)

Current smoker (n (%)) 13 (26) 29 (26) 31 (48)Pack-years* 12 (1, 33) 21 (4,40) 14 (5, 37)Age at start of smoking* 16 (13, 19) 17 (15,20) 17 (13,21)

PUR welding:Start, calendar year* 1980 (1970, 1987) 1974 (1968, 1984)Cumulative working days* 755 (240, 2710) 340 (40, 2820)Working days past month* 7.8 (0, 20)End of exposure* - 1988 (1979, 1991)

Ordinary welding:Start, calendar year* 1975 (1954, 1986) 1959 (1948, 1974)Cumulative working days* 1528 (0, 5390) 2690 (930, 5280)

Presently exposed (n (%)) 32 (73) 83 (64)Working days past month* 7.5 (0,20) 5 (0, 20)

* Median (10th, 90th percentile).

ing 65 men we obtained a response to theenquiry from 41.Exposure data were obtained from a ques-

tionnaire and at a personal interview (seebelow for details). Fifty men (31% of theparticipants) had been engaged in PURpipelaying during the three months immedi-ately preceding the examination day. Thesemen formed a subset of presently active PURpipelayers. The remaining 113 men are herecalled formerly active PUR pipelayers. Of these,89 men were still working as pipelayers,whereas 24 men had left the profession sixmonths or more before the investigation.The presently active PUR pipelayers were

further subdivided into one group with recenthigh exposure-that is, >10 working days ofPUR welding during the month preceding theexamination (n= 19; median 20 work days)-and one group with recent low exposure-that is,S 10 work days, (n= 31; median 0 work days).Table 1 gives descriptive data on exposure

for all participating pipelayers. The presentlyactive PUR pipelayers had a higher estimate forlifetime cumulative days of PUR welding thanthe formerly active men, but a lower estimatefor cumulative days of ordinary welding.Within the group of presently active PURpipelayers a similar difference was noted; thosewith recent high exposure had as a median1640 (1 Oth, 90th percentile 390,3920) lifetimePUR welding days, whereas the group withrecent low exposure had 500 (130, 1740) suchdays. The corresponding estimated cumulativeworking days with ordinary welding were 190(0, 2100) and 2400 (480, 5900) respectively.Even though the men with recent highexposure were younger than those with recentlow exposure (33 (22, 53) v 44 (25, 53) years),the median duration of PUR exposure wassimilar (11 years in both groups).The examination took place at the end of

1991 and the beginning of 1992. Shortly after-wards, many pipelayers terminated their workbecause of a crisis in the building sector.Hence, in 1993 the questionnaire was onceagain sent to the group of 50 presently activePUR pipelayers, and was returned by 44 of

them. Seventeen were still active in PUR work,whereas 27 had finished work. These groupsdid not differ with respect to age. Dataobtained in 1991-2 indicated that these groupshad similar tobacco consumption, whereas themen still active in 1993 had higher cumulativeexposure to PUR (825 (280, 4000) days) com-pared with those who had finished working(645 (192, 2622) days).

Generally, there were two main categories ofPUR pipelayers. One category consisted ofpipelayers almost exclusively engaged in theconstruction of district heating pipe systems.Often they were employed in small companies,specialised in this type of job. At the time ofinvestigation about 40% of the presently activePUR pipelayers were of this type.For the rest, the main type of work task was

mixed pipelaying and plumbing, including thewelding of ordinary non-insulated pipes. Nowand then they welded PUR insulated pipes,when connecting the internal pipe system of abuilding with the district heating pipe system.In the 1970s, when district heating pipesystems were first installed in many communi-ties, PUR pipelaying occurred more often thannowadays for several of these men.

Earlier work practices often included theburning off of the foam insulation by a gastorch before welding; such practices werereported by one third of the pipelayers in ourstudy. Later on, careful manual removal of atleast 25 cm of the foam before welding wasrecommended. Either gas or manual metal arcwelding was used. The use of personal protec-tion devices had been very limited; only 7% ofthe men reported that they often or always useda half mask respirator. Foaming at the junctionsites after welding was usually performed byspecialised workers not included in the presentstudy, but 15% of the pipelayers reported thatthey often or always used to foam MDI-basedPUR.

CONTROLSDuring the same time period as the pipelayerswere examined, we investigated the meta-choline reactivity in a working population, notpresently exposed to airway irritants. Thispopulation included both blue and white collarworkers from a pharmaceutical company,companies producing medical equipment andprinted matters, shop assistants, postmen,paramedics, and radiology technicians. Volun-teers were recruited, the only exclusion criteriabeing "almost daily use of asthma medicationsor use of peroral cortisone medication for anyother reason". Only lifelong non-smokers andpresent smokers were eligible. For the presentstudy, we selected all men in the same agerange as the pipelayers as controls, in total 65men (table 1).

QUESTIONNAIRESA detailed questionnaire was sent by mail to allparticipants (pipelayers and controls) abouttwo weeks before the examination. Majorrespiratory symptoms (dyspnoea, wheezing,and cough; translated from the British MedicalResearch Council questionnaire'), own and

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family allergy, previous pulmonary or cardiacdisease, and questions directed at symptomsindicative of non-specific bronchial hyperreac-tivity were recorded. A lifetime employmenthistory was reported, as were exposures tospecified dusts, chemicals, and contact withanimals during work or leisure time. The ques-tionnaire also consisted of additional questionson the prevalence and frequency of specifiedsymptoms from the eyes, nose, throat, andchest. Symptoms during the past year and ear-lier in adult life (for the pipelayers explicitlystated as the period before PUR pipelayingstarted) were recorded separately.A detailed smoking history was also obtained

from the questionnaire. The smoking habitsamong the pipelayers cannot be directlycompared with those among the controls, asex-smokers were excluded by definition fromthe second group. However, the daily amountof tobacco smoked was similar among activesmokers, regardless of exposure state (table 1).

INTERVIEWIn a standardised interview at the examinationa trained occupational health nurse (KKD)obtained information from the pipelayersabout their detailed work history and theirwork habits during pipelaying and weldingoperations. Thus, the lifetime cumulativenumber of working days and the number ofworking days with welding of PUR pipes andwelding of other pipes (also including otherwelding experiences) could be calculated. Thecorresponding figures were obtained for thepreceding three months and one month. Dayswith part time work with a certain task wereconverted to eight hour working days. Supple-menting questions on specific symptoms fromthe eyes, nose, throat, and chest, and their rela-tion to PUR welding were also asked, withoutregard to noted respiratory complaints in theself administered questionnaire.

SKIN PRICK TEST AND ASSAYS OF SPECIFICIMMUNOGLOBULINS E AND GFor pipelayers and controls a skin prick testwith 13 standard extracts (ALK, Copenhagen),a positive (histamine, 3 Hep), and a negativecontrol was performed. For the pipelayersadditional skin prick tests with isocyanate con-jugates with human serum albumin wereadded.6 The specific isocyanates used were4,4'-MDI (which is normally the main compo-nent in technical grade MDI), toluene diisocy-anate (commercial grade; 2,4- and 2,6-isomers),phenylisocyanate, p-toluene monoisocyanate,and 1,6-hexamethylene diisocyanate. The whealsize and shape were recorded on a transparenttape after 15 minutes. A wheal that was at leasthalfthe size ofthe histamine wheal was scored aspositive. Atopy was defined as a positive skinreaction to at least one of the standard extracts.There was no difference between the PURpipelayers and the controls in the prevalence ofatopy (22% v 25%).Radio allergosorbent test (RAST) and en-

zyme linked immunosorbent assay (ELISA)tests for specific IgE and IgG antibodies

respectively, against MDI conjugates withhuman serum albumin were also performed,including serum samples from 49 of thecontrols.6 For IgE-MDI, specific binding>0.3% was considered positive (highest control0.1%). For IgG-MDI, values exceeding thehighest value in the controls (IgG-MDI 0.14A) were regarded as positive.

LUNG FUNCTION TESTVital capacity (VC) and forced expiratory vol-ume during one second (FEV,) were deter-mined before and 15 minutes after administra-tion of a B-agonist (two inhalations of BricanylTurbohaler). The lung function tests were per-formed as recommended by the AmericanThoracic Society,'0 using a Vitalograph. Thesame test procedure was used for pipelayers andcontrols. The exposure state was not blinded forthe technician performing the test. The VC andFEV, were expressed as % predicted, using anexternal reference equation." Metacholinereactivity was also investigated (results notreported here).

STATISTICSThe prevalence odds ratio (POR), adjusted forpotential confounders was used for measuringthe effect of exposure to PUR." The focus ofinterest was on the one year prevalence of dif-ferent types of symptoms. Effect estimationswere performed by logistic regressions. Age(645, >45 years), atopy (yes, no), and smoking(lifelong non-smoker, ex-smoker, smoker) wereconsidered. Several categorical exposure vari-ables were explored. The categorisations wereas follows: exposure state (PUR pipelayer, con-trol), present exposure state (presently active,formerly active), cumulative days for PURwelding (, 500, >500), cumulative days forordinary welding (62500, >2500), days withPUR welding last month, 10, >10), yearssince end of PUR welding (0.25-5, >5). Forthe lung function variables linear regressions,adjusted similarly for potential confounders,were performed. Here, age was treated as acontinuous variable. Ex-smokers were omittedfrom the analyses when pipelayers and controlswere compared, whereas they were included inthe internal comparisons.For statistical testing we used Fisher's exact

test for binary variables, and the Mann-Whitney U test for continuous variables. Alltests were two tailed. The different statisticalmethods were performed as generally de-scribed. '3

ResultsSYMPTOMSThe prevalence of episodes (more than once amonth) of irritative eye symptoms, congestionof the nose (blocked nose), and soreness ordryness in the throat (throat irritation) duringthe year preceding the examination was muchhigher among the PUR pipelayers than amongthe controls (table 2). This was especially pro-nounced among the non-smokers. Also, thepipelayers reported a higher prevalence ofsymptoms from the lower airways, such as pro-

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Table 2 Symptoms during the year preceding the examination among PUR pipelayers and controls (questionnaire data)

PUR pipelayers Controls Pipelayers v controls

Non-smokers Ex-smokers Smokers Non-smokers Smokers(n=43) (n=78) (n=42) (n=34) (n=31)

Non-smokers PR Smokers PR Adjusted PORn Prevalence n Prevalence n Prevalence n Prevalence n Prevalence (95% CI) (95% CI) (95% CI)

Eye irritation* 11 0.26 16 0.21 11 0.26 3 0.09 3 0.10 2.9 (0.9 to 9.6) 2.7 (0.8 to 8.9) 3.6 (1.3 to 9.5)Blocked nose* 12 0.28 14 0.18 9 0.21 2 0.06 4 0.13 4.7 (1.1 to 19) 1.7 (0.6 to 4.9) 3.7 (1.4 to 10)Throat irritation* 10 0.23 6 0.08 4 0.10 1 0.03 1 0.03 7.9 (1.0 to 59) 3.0 (0.4 to 25) 6.8 (1.4 to 32)Drycough* 6 0.14 10 0.13 6 0.14 2 0.06 7 0.23 2.4 (0.5to 1) 0.6(0.2to 1.7) 1.0(0.4to2.7)Productive cought 3 0.07 8 0.10 6 0.14 1 0.03 1 0.03 2.4 (0.3 to 22) 4.4 (0.6 to 35) 3.8 (0.8 to 1.9)Attacks of wheezing 6 0.14 23 0.29 11 0.26 1 0.03 3 0.10 4.7 (0.6 to 38) 2.7 (0.8 to 8.9) 3.8 (0.2 to 12)

or dyspnoeat

* Episodes more often than once a month.t On most days for more than three months.f Ever such episodes.PR = prevalence ratio; POR = prevalence odds ratio; from a logistic regression, controlling for age, atopy, and smoking habits (ex-smokers excluded).

Table 3 Prevalence ofsymptoms during the year preceding the examination among presently active andformer PURpipelayers (questionnaire data)

Formerly active

Presently active Time since end of exposure Presently active vformerly active

Recent high Recent low 0.25-5y > 5y (adjusted) PORexposure (n=19) exposure (n=31) (n=64) (n=49) (95% CI)

Eye irritation* 0.37 0.32 0.20 0.16 2.9 (1.2 to 6.9)Blocked nose* 0.37 0.26 0.16 0.20 1.6 (0.7 to 3.9)Throat irritation* 0.32 0.13 0.11 0.06 2.0 (0.7 to 6.1)Drycough* 0.16 0.16 0.16 0.08 1.1 (0.4 to 3.2)Productive cought 0.16 0.13 0.08 0.10 2.6 (0.8 to 8.4)Attacks of wheezing or dyspnoeat 0.32 0.19 0.25 0.24 1.3 (0.5 to 3.1)

* Episodes more often than once a month.t On most days for more than three months.t Ever such episodes.POR = prevalence odds ratio, obtained from a logistic regression, controllin for age, atopy, smoking habits, and cumulative exposure(PUR and other welding).

ductive cough (on most days for more thanthree months a year), attacks of dyspnoea andwheezing (ever such episodes). Logistic regress-ion models, including age, atopy, and smokinghabits in addition to exposure status (pipelayeror control) confirmed the findings.The presently active PUR pipelayers re-

ported the highest prevalence of eye, nose, and

Table 4 Relation between symptoms and PUR pipe laying among 163 pipelayers(interview data)

Symptoms SymptomsNo symptoms appearing appearing in Better onat work immediately the evening* weekends

Eyeirritation 114 41 8 42Blocked nose 134 17 12 12Throat irritation 130 28 5 28Dry cough 144 17 2 17Attacks of wheezing or dyspnoea 141 14 8 16

* Or immediately and in the evening.

Table S Prevalence ofsymptoms during the preceding year in 1991-2 and in 1993 inrelation to exposure state 1993 among 44 PUR pipelayers, who were all active in 1991-2(questionnaire data)

Questionnaire 1991-2 Questionnaire 1993

Active 1993 Not active 1993 Active 1993 Not active 1993(n1= 7) (n=27) (n1= 7) (n=27)

Eye irritation* 0.41 0.19 0.47 0.22Blocked nose* 0.35 0.15 0.35 0.22Throat irritation* 0.29 0.11 0.23 0.15Dry cough* 0.18 0.07 0.12 0.04Productive cought 0.18 0.07 0.04 0.07Attacks of wheezing or

dyspnoeat 0.17 0.07 0.18 0.15

* Episodes more often than once a month.t On most days for more than three months.t Ever such episodes.

throat symptoms (table 3). Logistic regressionmodels, including age, atopy, and smokinghabits in addition to present exposure statusconfirmed the findings, which, however, reach-ed significance only for eye irritation. Theprevalences of these symptoms decreased withincreasing time since the end of PUR pipelay-ing. In contrast, there was no difference in theprevalence of symptoms from the lower airwaysbetween presently or formerly active PURpipelayers (table 3). In logistic regression mod-els, the cumulative days of PUR welding andordinary welding were explored, showing nosignificant associations with any type of symp-toms. Nominally higher prevalences of symp-toms were reported among presently activepipelayers with recent high, compared to thosewith recent low PUR exposure.

In the interview, most of the pipelayers withsymptoms reported that these had started andoccurred in relation to the PUR welding tasks(table 4). The non-atopic workers reportedwork related symptoms as often as the atopicworkers; likewise there was no difference in thereports between workers with different smok-ing habits. The interval between start of PURwelding and the occurrence of any work relatedsymptom was long, with a median 9 (2,20)years. Atopic workers did not report a shortersymptom free interval than did non-atopicworkers.

Table 5 shows the results from the 1993questionnaire. The symptom prevalences werestable over time.

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SKIN PRICK TEST AND ASSAYS OF SPECIFICIMMUNOGLOBULINS E AND GNone of the pipelayers showed positive skinprick reactions against the specific isocyanateantigens used or positive IgE-MDI. Twopipelayers showed low IgG-MDI values (0.18and 0.30 A).

LUNG FUNCTIONTable 6 shows VC and FEV1 (expressed as% predicted) among all pipelayers and con-trols. In multiple linear regression models(using the observed value, adjusted for smok-ing habits, age, and height) a small effect ofexposure was found for FEVI (13=-O. 11 (P=0.1O)) but not for VC (table 6). Asexpected, smoking effects were evident for bothFEV, and VC.

Similarly, when presently active pipelayerswere compared with controls, the correspond-ing effect for FEV, was B=-0.2 1 (P=0.09). Theeffect was most pronounced among presentlyactive pipelayers with recent high exposure toPUR, having an estimated reduction ofFEVI of-0.3 1 (P=0.04), compared to controls. Thereduction among those with recent low expo-sure to PUR was less, (-0.1 1 (P>0.2)). In themodels, the estimated reduction among smok-ers was about -0.4 1 (P<0.001). No confound-ing effect of ordinary welding could be demon-strated. For VC no differences betweenpipelayers and controls were evident.

In internal comparisons among the pipelay-ers, including also ex-smokers, there were nosignificant differences in FEV, and VC be-tween presently and formerly active PURpipelayers, adjusting for age, height, and smok-ing habits. We explored the effects of severalother exposure indices (cumulative days ofPUR welding, cumulative days of ordinarywelding, time since end of PUR and ordinarywelding) in further models, but no significantexposure-response relations were disclosed forany of them. Likewise, a similar internalcomparison between men with recent high andrecent low PUR exposure did not show signifi-cant differences in FEV1.

NON-PARTICIPANTSAccording to information from the initial shortenquiry, or from the employer's lists, the dura-tion of PUR pipelaying was estimated to havebeen 1-12 months for 17 (26%) of the 65 non-

Table 6 Lungfunction in pipelayers and controls

VC FEV,

Lung function, expressed as % predicted*:PUR pipelayers:Non-smokerst 90 (78,101) 100 (87,115)Ex-smokerst 85 (71,102) 97 (76,115)Smokerst 88 (74,103) 91 (74,109)

Controls:Non-smokerst 95 (85,104) 104 (91,114)Smokerst 88 (75,104) 95 (79,107)

Linear regression modest:Exposure states - (> 0.10) -0.12 (0.10)Smoking -0.19 (0.02) -0.38 (< 0.01)AtopyS - (> 0.10) - (> 0.10)

* Reference equation from Berglund et al" .t Median (1Oth, 90th percentile).t Ex-smokers excluded; adjusted also for age, and height.§ f (in litres) (P value).

participants, and > 1 year for five (8%) ofthem.For the 163 participants the corresponding fig-ures, as obtained from these sources, were 34%and 45%. Among the 41 non-participants whoresponded to the short initial enquiry threemen (7%) reported work related symptomsfrom the eyes or nose, and five men (12%)reported work related airway symptoms. Incontrast, among the participants the corre-sponding figures were 32% and 43% respec-tively.

DiscussionWe have found that PUR pipelayers, comparedwith unexposed controls, experienced an in-creased prevalence of current irritative symp-toms from the eyes, nose, and throat. They alsoreported that such symptoms occurred indirect relation to PUR welding. The prevalenceof irritative symptoms was highest among thepresently active PUR pipelayers, and decreasedwith increasing time since last PUR exposure.The same pattern emerged for productivecough. A direct irritating effect of thermal deg-radation products of MDI based PUR is themost likely explanation to these findings.The presently active pipelayers with recent

high PUR exposure had a reduced FEVy com-pared with controls. A reduction of FEV, alsooccurred in the total PUR pipelayer popula-tion, but it was weaker. Attacks of wheezing ordyspnoea, symptoms indicating airway ob-struction, were nominally more prevalentamong pipelayers than among controls, but notmore prevalent among presently v formerlyactive pipelayers. When assessing the preva-lence of respiratory symptoms and signs in across sectional study population, such as thesubset of presently active pipelayers, a selectionbias may be introduced, because workers withrespiratory symptoms and signs may have leftthe PUR work task beforehand. This will leadto an underestimation ofthe true risk. This biasmay be present in the direct comparisonsbetween presently and formerly active pipelay-ers, but is reduced in the overall analyses inwhich formerly active PUR pipelayers areincluded.An aggravation of respiratory symptoms

from concomitant exposure to respiratory irri-tants at work and smoking may increase thetendency for smokers to quit their habit. Wehave reason to think that such interactions haveaffected our results, as we found four ex-smokers who had a clinical diagnosis of asthmaduring their work as PUR pipelayers, and oneex-smoker who had his asthma diagnosis whilehe was working as a pipelayer but before PURwelding started. All but one of them reportedaggravated symptoms during PUR welding,whereas the remaining subject stated that ordi-nary welding was equally symptom provoking.Thus, this may have resulted in an underesti-mation of the true risk for symptoms anddecreased lung function in the direct compari-sons between pipelayers and controls, as allex-smoking pipelayers were excluded. Four ofthe five ex-smoking asthmatic workers alsobelonged to the formerly active group. This

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could partly explain why we found no clearcutfindings indicating a persisting adverse effect ofexposure to the lower airways.The basis for recruitment to the study was

company reports of employees. We had nopossibility of investigating the completeness ofthese reports. However, for men still active aspipelayers or having related assignments, wethink that the losses should have been small, aswe recruited from all companies specialising inPUR pipelaying, and all other major pipelayingcompanies in the area. For pipelayers entirelyleaving their occupation there might be somelosses, which we cannot estimate. For identi-fied subjects who were non-participants, wehave some information, indicating less expo-sure and less symptoms, than among partici-pants.Another bias which may be operating is a

selection of healthy persons to the occupation.It was found that welders under the age of 30had a higher FEVy than a group of controls. 4 Inthis study we have no indications of a majorselection bias of this type. We did not find adifference in the prevalence of atopy, or adifference in the proportion ofmen with symp-toms earlier in adult life or before PUR workstarted when all PUR pipelayers and controlswere compared. We also found that VC andFEVI among controls and formerly active PURpipelayers under the age of 35 were very close(data not given). In contrast, young presentlyactive PUR pipelayers showed a reduction ofFEV, compared with controls. This is againcomparable with an exposure effect.Can we then attribute the excess of respira-

tory symptoms and decreased lung function inthe pipelayers to their exposure to thermaldegradation products from isocyanates? Theinvestigated pipelayers were exposed to a com-plex mixture of compounds, several of whichare well known respiratory irritants or sensitis-ers. High peak exposures to isocyanates andamines occur at thermal decomposition oftechnical quality MDI-based PUR, which initself has a complex isomeric composition, andmore complex and new isocyanate compoundsare formed.7 Aldehydes and other compoundsare formed from the degraded polyol ingredi-ent. Further, the gas or metal arc welding ofthemild steel pipes, which are sometimes coatedby a protective oil, yields various gaseous andparticulate air contaminants.'5 A recent over-view of the literature on respiratory effects ofwelding was presented by Sjogren and Ulfvar-son.'5 The prevalence of chronic (simple)bronchitis has repeatedly been increasedamong welders. Data are, however, conflictingas to whether non-smoking welders also havean increased prevalence of chronic bronchitis.Impaired spirometric values have been foundmainly for FEV,. In some studies the effect wasseen only in smokers, in others non-smokershave also been affected.'6 Although the interestin respiratory effects of welding fumes havefocused on the bronchi, it is evident that theupper airways can also be affected. Anincreased prevalence of symptoms from theupper respiratory tract has been described,

with chronic rhinitis as the most often reportedsymptom among shipyard welders.'7The outlined complexity of exposure indeed

merits caution in the internal comparisons. Weestimated the cumulative work days of PURand ordinary welding, based on the retrospec-tive self reports. These estimates are by naturesubject to uncertainties. Time since lastexposure to PUR is probably more accuratelydetermined. We also presume that recentworking days can be accurately reported. Otherfactors which could not be taken into account,not least individual work habits, may greatlyinfluence the exposure to the thermal degrada-tion products of MDI and the welding fumes.We have previously shown, in this study base ofpipelayers, that the number of welded PURpipes during the preceding three months(which closely parallels duration of such work)correlates positively with 4,4-methylenediani-line in plasma, a biomarker for exposure.8 Thepresent study group consists of pipelayers withvarying intensity and duration ofPUR pipelay-ing and ordinary welding, a prerequisite forseparation of the effects, but our exposureindices are crude. This may partly explain thedifficulties in showing exposure-response rela-tions in the internal comparisons. However, inthe group of presently active pipelayers it wasobvious that the group with recent highexposure to PUR had a greater decrement ofFEVI than the controls, whereas the group withrecent low exposure had not. This finding can-not be explained by concomitant ordinarywelding, as these men actually performed lessordinary welding during the preceding month,and also had fewer cumulative days of ordinarywelding, than the pipelayers with ongoingrecent low PUR exposure.We did not find any evidence of IgE

antibodies in any of the pipelayers, and onlytwo of them had antibodies of the IgG type.This is not remarkable, as the prevalence ofspecific antibodies may be low in cohorts ofworkers exposed to MDI.6 18The pipelayers were exposed to a complex

mixture of inhaled irritants. We have not triedto evaluate whether any of the workersincluded in the present study have "isocyanateasthma" in a strict sense. "Variable airflowlimitation causally related to exposure tonon-irritant levels of isocyanates",'9 cannotultimately be diagnosed without specific inha-lation challenges. Neither questions on theoccurrence and timing of obstructive symp-toms in relation to work,20 nor specific serumantibodies,2' are sensitive and specific enoughfor a strict diagnosis.

In summary, as in other groups of workers,'exposure to thermal degradation productsfrom MDI based polyurethane among thesePUR pipelayers was related to adverse effects.The symptoms and decrease in lung functioncannot be explained by ordinary welding expo-sure only. We found that four out of five menwho had obtained a clinical diagnosis ofasthma during PUR pipelaying or ordinarypipelaying work were atopic. However, we didnot find substantial differences in prevalence ofsymptom, reported work related symptoms, or

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Airway symptoms and lungfunction and products from MDI-based polyurethane

lung function between pipelayers with andwithout atopy. Thus, as has been pointed outbefore,22 pre-employment removal of atopicworkers out of the workforce cannot preventadverse exposure effects. The only possibility isto minimise the exposure to thermal degrada-tion products by using optimal working proce-

dures.

We acknowledge the cooperation of all the pipelayers and thecompanies. We thank Assistant Professor Hans Welinder forassistance with the immunological analyses. Grants wereobtained from the Swedish Council for Work Life Research andthe Faculty of Medicine, Lund University. The study wasapproved of by the Ethics Committee, Faculty of Medicine,Lund University.

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