Work-related late asthmatic response induced by latex allergy

Work-related late asthmatic response induced by latex allergy Giuliana Brugnami, MD, Alessandra Marabini, MD, Andrea Siracusa, MD, and Giuseppe Abbritti, MD Pemgia, Ita/y Background: The occupational uses of latex gloves" may be associawd with asthma. Hypersensitivity to latex has been shown to be IgE-mediated. The asthmatic reaction to latex is' usually early; however, the natural history of latex asthma is still unknown. Objective: The purposes of this study were to investigate asthmatic responses induced by natural rubber latex and to assess the long-term respiratory consequences of latex-induced asthma after removal from exposure. Methods- This report describes the clinical and immunologic study of six nurses with workrelated respiratory and skin disorders induced by the use of latex gloves. To determine whether the symptoms induced by latex gloves were IgE-mediated, we assessed latex IgE antibody levels by skin prick tests (SPTs) and RASTs with latex extracts. To confirm work-related latex reactions, we assessed respiratory symptoms, skin reactions, and F E V z after a glove exposure test and an inhalation provocation test with latex gloves. All subjects were followed up for 7 months to 7years after the first observation. Results: All subjects had positive SPT and R A S T responses to latex extracts, posflive double prick test responses to latex gloves, and negative SPT responses to cornstarch and common allergens. Ten atopic and 10 nonatopic control subjects had negative SPT responses to latex and cornstarch extracts and negative double prick test responses to latex gloves. In three subjects latex allergy was associated with allergy to fruit (banana and chestnu O. After the glove exposure test, four of six subjects had contact urticaria, all had rhinoconjunctivitis, and two had a late asthmatic response. The inhalation provocation test was pelfonned on four subjects: all had rhinoconjunctivitis, two had urticaria and late asthmatic response, and one had laryngeal edema. A late asthmatic response was recorded in four subjects. Three subjects continued to have chronic asthma, and four subjects had increased nonspecific bronchial responsiveness 7 months to 7 years after being assigned to duties' not involving latex gloves. Conclusions: This study of six nurses shows that latex is a potential cause of occupational asthma, rhinoconjunctivitis, and urticaria-angioedema. Latex seems to include antigens that elicit IgE-mediated hypersensitivity and may cause a late asthmatic reaction. Occupational asthma caused by latex may lead to permanent respiratory disability, even after removal from exposure. (J ALLERGY CL[N IMMUNOL 1995;96.'457-64.) Key words: Latex rubber, immediate hypersensitivity, late asthmatic response, urticaria, angioedema, asthma, occupational diseases, rhinitis, provocation tests, follow-up studies

The first r e p o r t e d case of an immediate hypersensitivity reaction to latex was described by Nutter in 1979.1 Natural rubber (latex) is obtained f r o m From the Department of Clinical Medicine, Pathology and Pharmacology, Occupational Medicine and Toxicology Section, University of Perugia. Received for publication Feb. 7, 1994; revised Sept. 7, 1994; accepted for publication Nov. 29, 1994. Reprint requests: Giuliana Brugnami, MD, Medicina del Lavoro e Tossicologia Professionale e Ambientale, Via E. dal Pozzo, 06122 Perugia, Italy. Copyright © 1995 by Mosby-Year Book, Inc. 0091-6749/95 $5.00 + 0 1/1/67116

Hevea brasiliensis. Its industrial application is widespread, and it is used for occupational (e.g., health care) and n o n o c c u p a t i o n a l purposes. T h e reactions to latex were shown to be IgEmediated. 1,2 T h e use of latex surgical gloves has been associated with contact urticaria, angioedema, rhinoconjunctivitis, asthma, and laryngeal edema.l, 3, 4 Most of the r e p o r t e d cases o f latex hypersensitivity reactions are work-related and occur in health care workers, 5 workers in glove-manufacturing plants, 6 or patients undergoing surgical procedures or internal examinations. 7 Asthmatic reac457

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J ALLERGYCLINIMMUNOL OCTOBER 1995

Abbreviations used

DPT: DV: GET: IPT: LAR: NSBH: PEF: PNU:

SPT:

Double prick test Diurnal variation Glove exposure test Inhalation provocation test Late asthmatic response Nonspecific bronchial hyperresponsiveness Peak expiratory flow Protein nitrogen unit Skin prick test

tions to latex are usually of early onset?, 6, 8 T h e natural history of latex asthma is unknown. T h e purposes of this study were to evaluate asthmatic responses induced by latex and to assess long-term respiratory consequences of latex-induced asthma after removal f r o m exposure. METHODS Study design

To determine whether respiratory and skin symptoms after latex glove exposure were IgE-mediated, we measured latex IgE antibody by means of skin tests and RAST with latex extracts. To confirm work-related latex reactions we assessed respiratory and skin symptoms and FEV1 after performing a latex glove exposure test (GET) in all subjects and an inhalation provocation test (IPT) with latex gloves in four subjects. To assess progression and long-term consequences of latex-induced asthma, all subjects were followed up for 7 months to 7 years after the first observation. Subjects

Subject i was a 29-year-old nonsmoking female nurse. She had been working in a gynecology and obstetrics unit, which required frequent use of latex gloves, since 1978. Her family history of atopy was negative. At 8 years of age she had anaphylactic shock caused by tetanus antitoxin. She had had mild contact dermatitis on ear lobes since 1981. In 1983 itching and an urticarial eruption in rubber-contact areas (i.e., hands) developed. Rhinoconjunctivitis would appear a few minutes after she wore rubber gloves; whereas cough, dyspnea, and wheezing appeared 6 to 7 hours later. She had not experienced these clinical manifestations previously. She noticed that wearing the gloves after washing them caused only slight urticaria and no respiratory symptoms. At the first evaluation in the hospital she was free of symptoms, and results of physical examination were normal. Results of skin prick tests (SPTs) with common allergens were negative, whereas results of patch tests were positive for nickel sulfate. Spirometry results were

normal. Methacholine challenge test showed moderate nonspecific bronchial hyperresponsiveness (NSBH). Subject 2 was a 40-year-old nonsmoker. She had been working as a nurse in an orthopedic unit and an operating room, where she used rubber gloves, since 1973. She had no personal or family history of atopy. She had never experienced contact dermatitis. In 1985 she had urticaria on her hands and forearms, rhinoconjunctivitis, and asthma; each time these symptoms were associated with wearing rubber gloves. At the first evaluation results of physical examination were normal. Results of SPTs with common allergens were negative. Results of patch tests were positive in response to some rubber additives (tetraethylthiuram, mercaptobenzothiazole). Spirometry results were normal, but she had slight NSBH. Subject 3 was a 40-year-old male nurse with a minimal smoking history. Since 1975, he had been working in a hospital ward and occasionally used rubber gloves. He had no personal or family history of atopy. He had never had contact dermatitis. He reported that starting in 1989, use of rubber gloves had caused itching of the hands, rhinoconjunctivitis, dyspnea, wheezing, and cough. At the first evaluation results of physical examination were normal. Results of SPTs with common allergens were negative. Patch testing showed a reaction to thimerosal. Spirometry results were normal, but he had slight NSBH. Subject 4 was a 26-year-old female nurse who was a former smoker. She had been working in the operating room since 1986. She had no personal or family history of atopy. She had never experienced contact dermatitis. In 1989 rhinoconjunctivitis and urticaria developed a few minutes after she donned rubber gloves. Eight months earlier she had also experienced slight dyspnea 30 minutes after wearing rubber gloves, which continued through the night. At the first evaluation results of physical examination and spirometry were normal. SPTs with common allergens showed negative results. She refused to undergo patch tests. She had slight NSBH. Subject 5 was a 42-year-old smoker with no personal or family history of atopy. She had been a nurse working in an endoscopic unit since 1988. Occasionally, she wore rubber gloves and experienced itching hands. Several months earlier, work-related contact dermatitis had developed. Four months after the first observation, she had two episodes, several hours after wearing rubber gloves, characterized by urticaria, eyelid angioedema, rhinitis, dyspnea, wheezing, and cough, At the first evaluation results of physical examination and spirometry were normal. Results of SPTs with common allergens were negative. Results of patch tests were positive in response to many haptens: benzalkonium chloride, glutaraldehyde, bergamot oil, and nickel sulfate. She had slight NSBH. Subject 6 was a 28-year-old nonsmoker. She had been

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J ALLERGY CLIN IMMUNOL VOLUME 96, NUMBER 4

working as a nurse in an intensive care unit since 1990 and used rubber gloves regularly. She had no personal or family history of atopy. She had never had contact dermatitis. In October 1991 she experienced rhinoconjunctivitis 1 hour after wearing rubber gloves. In early 1992 she had cough, dyspnea, and wheezing several hours after wearing rubber gloves, which continued through the night. Six months later, she had two episodes of asthma and rhinoconjunctivitis 2 to 3 hours after eating a banana and chestnuts, respectively. At the first evaluation she was free of symptoms, and results of physical examination were normal. Results of SPTs were positive for banana ( + + ) and chestnut ( + + + ) and negative for other fruits and common allergens. Results of patch tests were negative. Spirometry results were normal, but she had moderate NSBH.

Latex and cornstarch extracts Natural latex. One gram of latex from H. brasiliensis was extracted in 9 ml of physiologic saline solution with 0.3% phenol. After centrifugation, the latex extract used for SPTs was sterilized through a Millipore fiIter (0.22 ~xm; Millipore Corp., Bedford, Mass.) and diluted to 1:100 wt/vol (4199 protein nitrogen units [PNU]) with an unbuffered saline solution containing 0.03% human serum albumin and then diluted to 1:10 wt/vol (42,643 PNU) with phosphate-buffered saline. These extracts were provided by Bayropharm Italiana s.r.1. (Milano, Italy) and were used for both SPTs and RASTs. Washed gloves sample. Rubber gloves were left to soak for 1 hour in physiologic saline solution (1 mg:l ml wt/vol). Cornstarch extract. Cornstarch powder was diluted to 10 mg:l ml wt/vol in a 50% glycerosaline solution. Immunologic studies SPTs with common allergens, natural latex extract, glove washing sample, and cornstarch extract were carried out in the six subjects with latex hypersensitivity and in 10 atopic and 10 nonatopic control subjects. A lancet was used to prick a rubber glove, and immediately thereafter, to prick the skin (double prick test [DPT]). 9 The DPT was carried out with a latex glove coated with cornstarch powder and with a piece of glove washed with tap water for 15 minutes to remove cornstarch powder. Specific IgE to natural latex extract was measured by RAST with a standard technique (CAP system; Pharmacia Diagnostics AB, Uppsala, Sweden). The characteristics of this assay have already been reported, t° Results were expressed quantitatively in kilounits per liter and considered positive at values greater than 0.35 kU/L.

GET and IPT All subjects were adequately informed of the aims, methods, and potential hazards of GET and IPT and gave informed consent. G E T and IPT were performed

459

TABLE I. Characteristics of the six nurses studied

Subject No.

Age (yr)

Sex

Duration of exposure till first systemic reaction{yr)

1

29

F

7

2 3 4 5 6

40 40 26 32 28

F M F F F

1 16 4.3 4.2 3

Durationof symptoms inducedby latex (yr) 4

5 3 0.7 0.3 2

by experienced personnel in a hospital setting where resuscitation facilities were available. A G E T while subjects were wearing unwashed latex gloves (subjects 2, 3, 4, and 5) or while subjects were wearing one unwashed and one washed glove (subjects 1 and 6) was performed for 15 to 60 minutes. Symptoms and skin reactions were noted. FEVa was measured before exposure, after 15 and 30 minutes, hourly for 12 hours, and then at 24 hours after exposure. The day before the G E T a control test was performed in which all subjects wore washed rubber gloves for 30 minutes. The gloves had been washed in tap water for 15 minutes. IPT with latex gloves was carried out in subjects 1, 3, 4, and 6. They handled five pairs of latex gloves for 8 to 60 minutes, while their hands were protected by polyethylene gloves. Subject 5 was exposed to a mixture of cornstarch (30 gin) and lactose (60 gm) powder for 15 minutes. Symptoms and skin reactions were noted. FEV t was measured at the same time intervals as it was for the GET. The day before the IPT, a control test was performed in which subjects 1, 3, 4, and 6 were exposed to lactose for 30 minutes.

Methacholine challenge test A baseline methacholine challenge test was done for all subjects, and it was performed in five subjects 24 hours after GET or IPT. A breath-activated dosimeter (ME.FAR, Brescia, Italy) was used. Double cumulative doses of methacholine were administered, beginning with a dose of 25 p~g (25, 50, 100, 200, 400, 800, 1600, and 3200 p~g).la FEVa recorded after phosphate buffer (control reagent) inhalation was considered as baseline. FEV1 was recorded 1 minute later, followed by the next dose. The challenge sequence terminated when F E V a had decreased by 20% or more or when the maximum cumulative dose (3.2 rag) had been administered. The methacholine PD2o was obtained from the dose-response curve plotted in a semi-logarithmic scale; the abscissa represents logarithmic methacholine doses, and the ordinate shows the percentage decrease of FEV a. Challenge was performed with buffered lyophilized methacholine (phosphate buffer) (Lofarma, Milano, Italy); 0.2% and 2% methacholine solutions were pre-

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TABLE II. Immunologic data Skin tests Subject No.

Common allergens

Natural latex (1:100 wt/vol)

Natural latex (1:10 wt/vol)

Washed gloves sample

1 2

Negative Negative

++ ++

+++ +++

3 4 5

Negative Negative Negative

+ ++ +

6

Negative

+++

RAST* to latex extract

Total IgE (kU/L)

Cornstarch

DPT

++ +++

Negative Negative

+ ++

0.8 9.7

29 67

++ +++ ++

+ +++ ++

Negative Negative Negative

++ +++ ++

0.5 2.2 4.3

39 137 29

+++

++

Negative

++

36.5

226

Patch test

NS + + + TET + + MBT ++ T ++ ND BC + + G +++ BO ++ NS + + + negative

*Positive lower limit = 0.35 kU/L. NS, nickel sulfate; TET, tetraethylthiuram;MBT, mercaptobenzothiazole;T, thimerosal; Be, benzalkonium chloride; G, glutaraldehyde; BO, bergamot oil; ND, not done.

pared by diluting methacholine in distilled water. The dosimeter delivered methacholine from an MB2 ampule (ME.FAR) by means of an air compressor (driving pressure = 1.5 kg/cm2). 1l Every inhalation delivered 25 or 250 ~xg of methacholine from 0.2% and 2% concentrations, respectively. D i u r n a l v a r i a t i o n in p e a k e x p i r a t o r y f l o w

During follow-up, peak expiratory flow (PEF) was recorded three times a day for 2 weeks during work and during holidays. Diurnal variation (DV) in PEF was measured as the difference between highest and lowest daily values, expressed as a percentage of the highest value. RESULTS

Our study included one male and five female nurses with work-related respiratory and skin symptoms associated with rubber gloves (Table I). All subjects were hospital nurses. Work-related respiratory and skin symptoms started 1 to 16 years after using latex gloves and 4 months to 5 years before the first clinical observation. All had a positive SPT response to latex extracts (Table II). T h e highest concentration (1:10 wt/vol, 42,643 PNU) produced stronger reactions. All subjects had positive responses to DPT. All had negative SPT responses to cornstarch extract and c o m m o n allergens. Ten atopic and 10 nonatopic control subjects had negative SPT responses to latex and cornstarch extracts and negative D P T responses to latex gloves. Two subjects had a value of total IgE above 100 kU/L.

Significant R A S T binding to latex extract, ranging from 0.5 kU/L to 36.5 kU/L, was observed in all subjects. Four of the subjects had positive patch test reactions, but only one had a positive reaction to rubber chemicals. After the GET, four of six subjects tested had contact urticaria, one had eyelid edema, and all had rhinoconjunctivitis. Two had a late asthmatic response (LAR) (Table III). In subject 2 an LAP, started 6 hours after the G E T and lasted for at least 7 hours (Fig. 1). In subject 3 an LAR was not documented by FEV 1, but by PEF (Fig. 2), because it occurred at night and was associated with a marked increase in NSBH. (Methacholine PD20 was 505 ~g before exposure and 31 Ixg 24 hours after the GET.) After the IPT, which was interrupted after 8 minutes because of conjunctival symptoms, subject 1 had immediate urticaria and rhinitis, as after the GET, and LAR started 7 hours after exposure and lasted for 3 hours (Fig. 1). She also had laryngeal edema, which was treated with epinephrine (0.33 mg administered subcutaneously) 30 minutes after exposure. In subject 3 the IPT (30 minutes) determined immediate rhinoconjunctivitis and facial itching. In subject 4 the G E T and the IPT (60 minutes) produced the same response (immediate urticaria and rhinoconjunctivitis). After the IPT (60 minutes), subject 6 had slight rhinoconjunctMtis immediately after the test, and LAR started 6 hours after exposure and lasted for at least 2 days (Fig. 1). A previous IPT for 30 minutes and a G E T produced immediate rhinoconjunctivitis but not LAR.

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B r u g n a m i et al.

lbU e-

461

Lactose (30 min)

•

Inhalation provocation test (8 min)

140

Exposure

120

Subject

~1. A d r e n a l i n e

,.¢1

(0,33

1

ml)

100 80 Lu i.i.

6O . . . .

4O

-10

0

Minutes

160 .=

// . . . .

15 30

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140

1

2

,

.. . . . .

3

4

5

6

7

Hours

8

9

,

10 11

,//, 12 24

Washed glove exposure test (30 min) Glove exposure test (30 min)

Exposure

Subject

2

o~ 120

J~

100 80 LM U.

60 40 -10

0,, 15 30 Minutes

*

160

1.

.2 . 3 . 4 .

; . ;. 7 ; 9 Hours

10 11

1,//2,

Lactose (30 rain) Inhalation provocation test (60 min)

140 u)

Subject

6

120

.ci o~

100 80

LU n

60

40

'

-

0 0

,

.

15

2

Minutes

.

.

3

.

4

.

5

.

.

6

.

7

.

.

8

Hours

.

9

//,

//,

10 11 12 24 48

FIG. 1. LARs after IPT (subjects 1 and 6) or GET (subject 2).

In subject 5 there were no respiratory or skin responses after the bronchoprovocation test (15 minutes) with cornstarch powder. Methacholine PDa0 at the first observation showed a variable degree of NSBH in all subjects (Table III). In subjects 3, 4, and 6 there was an increase in NSBH 24 hours after the GET or the IPT. All subjects were studied again 7 months to 7 years after the first observation. During follow-up, five subjects changed jobs and entered work environments where they did not wear rubber gloves,

but subject 4 continued to use rubber gloves lubricated with a hydrogel. Subjects 1, 2, and 3 continued to have asthmatic symptoms and increased variability in PEF and NSBH 1 to 7 years after the first observation (Table IV) although they no longer wore rubber gloves. In two subjects (1 and 3) there were no differences in DV in PEF between work days and days away from the workplace. Coworkers did not wear rubber gloves, and in the work environment there was no central ventilation system (another possible source of latex aerosol).

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J ALLERGYCLIN IMMUNOL OCTOBER 1995 800

Subject

700 600

3

Exposure

A

e"

.m

E

500

..1

400

14. ILl I1.

300 200 100

505

0

PD20 I

1

I

I

I

2

methacholine I

I

3

(gg)

31

I

4

I

5

6

Days FiG. 2. LAR after GET associated with an increase in bronchial responsiveness.

TABLE III. Effect of GET or IPT on FEV1 and bronchial reactivity to inhaled methacholine

Subject No.

Type of exposure

Duration of exposure (min)

1 2 3 4 5 6

IPT GET GET IPT GET IPT

8 15 60 60 30 60

Maximum fall in FEV1

Methacholine PDzo (Isg)

Baseline FEV~ (% pred)

EAR

LAR

Before*

After*

109 122 115 101 121 105

-3 +5 +7t -5 -3 -13

-26 -30 -25t -7 -11 -48

233 950 505 533 1540 175

ND 700 31 128 2488 35

EAR, Early asthmatic response; ND, not done. *Before the challenge test and 24 hours after the challenge test. tMaximum fall in peak expiratory flow.

During follow-up, two subjects demonstrated allergy to fruit. Subject 2 had urticaria and laryngeal edema 30 minutes after eating a banana. Subject 5 had only two mild episodes of asthma and rhinoconjunctivitis 2 to 3 hours after eating a banana or drinking tropical fruit juice. DISCUSSION This study shows that skin and respiratory symptoms associated with the use of rubber gloves are IgE-mediated hypersensitivity reactions to latex. Four subjects had LARs to challenge testing with rubber gloves, and three subjects had chronic asthmatic symptoms i to 7 years after job reassignment during which latex gloves were not used. An indirect exposure to latex was unlikely because none of the coworkers used latex products. In subjects with work-related skin and respira-

tory symptoms caused by rubber gloves, IgE-mediated hypersensitivity to latex extract has been demonstrated repeatedly. 1, 2. 12-14We also confirm, by means of SPT and RAST, that symptoms caused by the use of rubber gloves were associated with specific IgE to latex extracts in skin and serum. In fact, the six subjects described in this study had positive reactions to SPTs with all latex extracts, positive DPT responses to rubber gloves, and significant RAST binding to latex extract (Table II). The reaction to SPTs with latex was specific, as it was negative in all atopic and nonatopic control subjects. DPT was as sensitive as SPT and RAST with latex extracts. DPT with latex gloves could be a simple, sensitive, and specific method for detecting latex hypersensitivity. Cross-reactivity between latex and fresh fruits such as banana, avocado, and chestnut has been

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TABLE IV, Respiratory symptoms, use of medications, lung function, and bronchial reactivity at

follow-up

Subject No.

Follow-up (yr)

Frequency of asthmatic symptoms

1

4 6 7 1 3 4 1 2 2 1 0.6

Daily Daily Daily Weekly Weekly None Weekly Weekly None None Episodic

2

3 4 5 6

DV in PEF (mean _+ SD)

Use of antiasthma medications

FEV 1 (% pred)

Nlethacholine PDzo (l~g)

Daily Daily Daily Weekly Weekly None Weekly Weekly None None None

82 79 73 101 112 117 115 126 104 118 101

54 24 60 450 >3200 >3200 1220 532 ND >3200 118

At work

Away from work

17.9 + 6.8

14.3 + 5.4

17.3 -+ 2.2

11.4 +_ 3.7

20.8 _+ 7.3 ND ND 4.1 +_ 2.5

25.8 _+ 4.8 ND ND 3.2 + 1.5

ND, Not done.

previously reported. ~5-~7Latex hypersensitivity can follow 15 or precede ~6, 17 fruit allergy. We confirmed these observations of fruit allergy in three subjects with preexisting latex hypersensitivity. Three subjects had positive patch test results with work-related antigens. However, the best available evidence suggests that the LAR is dependent on the presence of allergen-specific IgE, 18 and it is not due to delayed-type hypersensitivity to environmental allergens. By means of G E T and IPT, we were able to confirm work-related respiratory and skin symptoms as noted in previous studies?, 7, 19 It is very likely that bronchial inhalation of latex antigens is higher with the IPT than with the GET. Consequently, it was not unexpected that two subjects had an L A R after the IPT but not after the GET. It is more ditficult to explain why subject 3 had an LAR after the G E T and only rhinoconjunctivitis after the IPT. Asthmatic reactions to latex are usually early?, 6, 7, 19-21 In this study we report four cases of LAR, three of which were documented by monitoring F E V 1 for 12 hours after exposure and then at the twenty-fourth hour. In one subject an immediate reaction might have been prevented by early treatment with epinephrine because of laryngeal edema. Previous studies regarding inhalation challenges with latex had methodological problems. Seaton et al. 2° monitored P E F for an unspecified time after exposure, Baur and Jager 21 monitored airway resistance for 21/2 hours, Jaeger et al. 8 and Tarlo et al. 6 monitored F E V 1 for 5 hours, and Lagier et al? monitored F E V 1 for 4 hours and then at the seventh hour. Finally, the method used by

Pisati et al. 22 was able to detect early and dual, but not isolated, late asthmatic reactions. According to the "Guidelines for bronchoprovocation on the investigation of occupational asthma, ''23 monitoring of lung function should be carried out for at least 8 hours. A late reaction might escape a short period of monitoring FEV 1. To our knowledge, this is the first documentation of LARs induced by latex. Three subjects continued to have respiratory symptoms and increased NSBH even though they stopped wearing rubber gloves after reassignment to new jobs. In addition, coworkers did not wear rubber gloves. There was no difference in D V in PEF between workdays and days away from the workplace. It is reasonable to conclude that in those subjects there was neither a continuous occupational exposure nor an incidental exposure to latex. Persistence of symptoms and increased NSBH in patients with occupational asthma removed from exposure have been demonstrated in previous studies. 24-26 This study demonstrates that occupational asthma caused by latex can lead to chronic asthma, even when latex exposure has been eliminated. In summary, latex has been shown to be a potential cause of occupational asthma, rhinoconjunctivitis, and urticaria-angioedema. Antigens in latex appear to elicit IgE-mediated hypersensitivity. Asthmatic reactions to latex may be early or late. Occupational asthma caused by latex may lead to permanent respiratory disability, even after removal from exposure. We thank Helen Dimich-Ward for her critical review of the manuscript, Laura Traica and Eileen Mahoney

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Zannetti for excellent editorial and secretarial assistance, and Bayropharm Italiana s.r.1. (Milano, Italy) for providing the latex extract used for SPTs and RASTs. REFERENCES

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