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Journal of Occupational & Environmental Medicine:
Original Articles

Prevalence and Onset of Rhinitis and Conjunctivitis in Subjects with Occupational Asthma Caused by Trimellitic Anhydride (TMA)

Grammer, Leslie C. MD; Ditto, Anne M. MD; Tripathi, Anju MD; Harris, Kathleen E. BS

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From the Division of Allergy-Immunology and the Ernest S. Bazley Asthma and Allergic Diseases Center of the Department of Medicine of Northwestern Memorial Hospital and Northwestern University Medical School, Chicago, Illinois.

Address correspondence to: Leslie C. Grammer, MD, Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Allergy-Immunology, MC S207 Tarry Building 3–713, 303 E Chicago Ave, Chicago, IL 60611; e-mail:

Supported by the Ernest S. Bazley grant to Northwestern Memorial Hospital and Northwestern University Medical School, and by the BP Amoco Corporation.

Copyright © by American College of Occupational and Environmental Medicine

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Individuals with occupational asthma may also report symptoms of rhinitis or conjunctivitis. The objective of this study was to investigate the prevalence of rhinitis and conjunctivitis in subjects with occupational asthma as a result of trimellitic anhydride (TMA). Additionally, we wanted to evaluate the onset of rhinitis and conjunctivitis symptoms as compared with the occupational asthma symptoms. In a case series design, we studied 25 consecutive employees with TMA-induced asthma; each of them had participated in an annual surveillance program in which they were queried about rhinitis, conjunctivitis, and other respiratory symptoms. Twenty-two of the 25 (88%) reported rhinitis symptoms whereas 17 of the 25 (68%) reported conjunctivitis symptoms. In 17 of the 22 (77%) individuals with rhinitis and asthma, the rhinitis symptoms preceded the asthma symptoms. In 14 of the 17 (82%) individuals with conjunctivitis, those symptoms preceded the asthma symptoms. In summary, symptoms of rhinitis and conjunctivitis are common in subjects with occupational asthma because of TMA and often precede the respiratory symptoms.

The prevalence of occupational rhinitis and conjunctivitis is unknown but occur commonly in those individuals exposed to agricultural gases, vapors, fumes, and dust. 1 A survey study of occupational rhinitis in Finland reported that 20% of rhinitis in that country was occupational. The most common exposures occurred in agricultural environments, examples being flour, animal dander, and wood dust. 2 The symptoms of rhinitis and conjunctivitis are probably more common and more significant in persons exposed to high molecular weight agents as compared to low molecular weight agents, which can cause disease by non-IgE–mediated mechanisms. 3

Unlike many other low molecular weight chemicals, the occupational asthma caused by trimellitic anhydride (TMA) CAS No. 552-30-7 appears to be IgE mediated. 4 The prevalence and onset of symptoms of rhinitis and conjunctivitis have not been prospectively evaluated in subjects with occupational asthma because of low molecular weight chemicals, such as anhydrides, that are IgE mediated. We hypothesized that just as rhinitis induced by high molecular weight agents tended to precede asthma, individuals exposed to TMA would also develop rhinitis and conjunctivitis prior to the onset of asthma.

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Study Population

The study population was composed of 25 consecutive employees diagnosed with TMA asthma. Criteria for the diagnosis have been published previously. 4 Each subject gave written, informed consent, and the study was approved by the Institutional Review Board (IRB) at Northwestern University.

Each of these 25 individuals was in a surveillance program in which clinical and immunologic evaluation was performed on an annual basis. A questionnaire modified from that developed by the National Institute for Safety and Health and the University of Cincinnati was administered to each employee. 5 The questionnaire was formulated to elicit type, timing, and severity of symptoms. Demographic data were also obtained.

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Analysis of Results

We compared those 17 individuals who developed rhinitis and conjunctivitis prior to the onset of their asthma with eight individuals who did not. Chi-square or Fisher’s exact test were used to compare demographic data. A two-sample t test assuming unequal variances was used to compare time to onset of symptoms. All were performed with Microsoft Excel Spreadsheet data analysis software.

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The majority of the 25 individuals with TMA asthma also reported TMA rhinitis (22/25 = 88%). Symptoms of conjunctivitis were less common, but very prevalent (17/25 = 68%). The majority of the 25 individuals who reported TMA asthma had symptoms of rhinitis and conjunctivitis that predated their asthma symptoms (17/25 = 68%). Of the eight individuals who did not have prodromal rhinoconjunctivitis symptoms, three never reported such symptoms and the other five had simultaneous onset of their asthma and rhinoconjunctivitis symptoms within 3 months of exposure to TMA.

Table 1 is a compilation of the demographic and temporal information on the 25 individuals with occupational asthma due to TMA; they are divided into two groups, those in whom rhinoconjunctivitis preceded asthma and those in whom it did not. There are no significant differences in the demographic data of the group, nor are there differences in onset of asthma symptoms (2.6 ± 4.4 years vs 1.4 ± 12.1 year;P = 0.19). There are differences in onset of rhinitis and conjunctivitis symptoms in the five individuals who had the simultaneous onset within 3 months of asthma and rhinoconjunctivitis symptoms as compared to the 17 in whom the latter symptoms came first (1.8 ± 2.7 years vs 0.19 ± 0.003 years;P < 0.0003).

Table 1
Table 1
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It is well known that in the nonoccupational setting, rhinitis and conjunctivitis often accompany asthma. 6 This association has been less well studied in the occupational setting. Malo and coinvestigators 7,8 described rhinoconjunctivitis being more common than occupational asthma in individuals with high-risk exposures. For example, it occurred in 32% of 193 health care employees exposed to psyllium and in 36% of individuals exposed to guar gum in carpet manufacturing.

Cartier et al 9 have described several etiologies of occupational asthma with a latency period that are associated with rhinoconjunctivitis. In a study of snow-crab processing employees, 76% of those with occupational asthma had occupational rhinitis as well. In the case of high molecular weight agents, the rhinoconjunctivitis and asthma are IgE mediated whereas with low molecular weight agents, such as isocyanates, the immunopathogenesis is not clearly understood, and occupational rhinitis is much less common. When rhinitis or conjunctivitis occur, they tend to have onset concurrently with the asthma symptoms. 3

The acid anhydrides cause occupational asthma by an IgE-mediated mechanism. 4 Therefore, it is probably not surprising that rhinoconjunctivitis precedes occupational asthma in many of these individuals, just as it does in asthma caused by high molecular weight agents. Perhaps, in some industries, the onset of rhinoconjunctivitis symptoms could be cause for transfer to a workstation with a lower level of exposure. Whether most individuals with occupational rhinitis go on to develop occupational asthma has not been studied, and thus, at this point, there are no data to suggest that individuals who only have upper airway symptoms should be advised to avoid exposure.

In summary, as with other IgE-mediated causes of occupational asthma, asthma caused by the acid anhydride, TMA, is commonly preceded by symptoms of occupational rhinitis and conjunctivitis. Determining the risk of developing occupational asthma subsequent to onset of symptoms of rhinoconjunctivitis is an important question that we are beginning to study.

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1. Meltzer EO. Antihistamine and decongestant-induced performance decrements. J Occup Med. 1990; 32: 327–334.

2. Kanerva L, Vaheri E. Occupational rhinitis in Finland. Int Arch Occup Environ Health. 1993; 64: 565–568.

3. Malo J-L, Lumiere C, Desjardins A, Cartier A. Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma. Eur Respir J. 1997; 10: 1513–1515.

4. Grammer LC, Patterson R, Rom WN. Trimellitic Anhydride in Environmental and Occupational Medicine, 3rd ed. Philadelphia: Lippincott-Raven; 1998: 1215–1219.

5. Bernstein DI. Clinical assessment and management of occupational asthma. In: Bernstein IL, Chan-Yeung M, Malo J-L, Bernstein DI, eds. Asthma in the workplace, 2nd ed. New York: Marcel Dekker Inc.; 1999: 145–157, 731–734(appendix).

6. Greenberger PA, Grammer LC. Asthma in Patterson’s Allergic Diseases, 6th ed. Philadelphia: Lippincott; 2002: 445–513.

7. Malo J-L, Cartier A, L’Archevêque J, et al. Prevalence of occupational asthma and immunologic sensitization to psyllium among health personnel in chronic care hospitals. Am Rev Respir Dis. 1990; 142: 1359–1366.

8. Malo J-L, Cartier A, L’Archevêque J, et al. Prevalence of occupational asthma and immunologic sensitization to guar gum among employees at a carpet-manufacturing plant. J Allergy Clin Immunol. 1990; 86: 562–569.

9. Cartier A, Malo J-L, Forest F, et al. Occupational asthma in snow crab processing workers. J Allergy Clin Immunol. 1984; 74: 261–269.

©2002The American College of Occupational and Environmental Medicine


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