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Risk of Asthma Among Finnish Patients With Occupational Rhinitis^*

^* Department of Epidemiology and Biostatistics (Dr. Karjalainen and Mr. Martikainen), Finnish Institute of Occupational Health, Helsinki, Finland; Social Insurance Institution (Dr. Klaukka), Helsinki, Finland; and Tampere Regional Institute of Occupational Health and Clinic of Occupational Medicine (Drs. Saarinen and Uitti), Tampere University Hospital, Tampere, Finland.

Correspondence to: Antti Karjalainen, MD, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland; e-mail: antti.karjalainen{at}occuphealth.fi

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study objectives: To determine the risk of asthma among patients with occupationally induced rhinitis.

Design: Patients with confirmed occupational rhinitis were followed for asthma incidence through register linkage. Patients with other occupational diseases were used as a reference population.

Subjects: Patients entered into the Finnish Register of Occupational Diseases in from 1988 to 1999 for occupational rhinitis (n = 3,637) or other occupational disease (n = 31,457) were observed until December 31, 2000, through two national registers of individuals who were eligible for the reimbursement of asthma medication and the Population Register Center.

Methods: Incidence rates of asthma were calculated, and a log-linear model, adjusted for age, gender, and occupation, was used to estimate the relative risks (RRs) of asthma among those with occupational rhinitis compared to those with other occupational diseases.

Results: There were 420 and 972 incident cases of asthma, respectively, among those with occupational rhinitis and the reference population. The crude RR of asthma was 4.8 (95% confidence interval [CI], 4.3 to 5.4) for all patients with occupational rhinitis, 5.4 (95% CI, 4.8 to 6.2) for those with occupational rhinitis accepted for compensation, and 3.7 (95% CI, 3.1 to 4.5) for patients with unaccepted occupational rhinitis. The RR varied according to occupation and was the highest among farmers and wood workers, both groups having a sevenfold risk. The risk was especially high during the year following notification, but a roughly threefold risk persisted several years thereafter.

Conclusions: Patients with occupationally induced rhinitis have a high risk of asthma, but further studies are needed to establish the effect of preventive interventions.

Key Words: asthma • epidemiology • incidence • rhinitis • risk

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Epidemiologic aspects of occupational rhinitis are less established than those of occupational asthma.¹ In Finland, furriers, bakers, and animal husbandry workers (livestock breeders) have the highest relative risk (RR) of occupational rhinitis.² Many of the causative agents of occupational asthma are also capable of inducing occupational rhinitis. These agents are usually divided into low-molecular-weight compounds (various chemicals) and high-molecular-weight compounds (eg, animal-derived or plant-derived proteins). Compared with asthma, rhinitis seems to be less common after exposure to low-molecular-weight compounds than after exposure to high-molecular-weight compounds.¹

Patients with occupational asthma frequently report symptoms of occupational rhinitis, and, according to case reports and retrospective studies, the rhinitis may have started before the asthma.³ While perennial rhinitis has been established as an independent risk factor for asthma,⁴ there are no prospective studies on the incidence or risk of asthma among persons with occupational rhinitis. Among Canadian patients with occupational asthma, symptoms of rhinitis were reported by 92%.⁵ For about half of the patients, retrospective assessment indicated that rhinitis symptoms began before the asthma symptoms, especially among those with occupational asthma caused by exposure to high-molecular-weight compounds. Yet, rhinitis is a common condition among the working population, and therefore the cross-sectional design of the Canadian study did not allow any conclusions to be drawn as to the predictive value of symptoms of rhinitis in regard to the development of occupational asthma.

In the present study, our objective was to determine the risk of asthma among Finnish patients with occupational rhinitis.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study Population
The study population consisted of nonasthmatic patients entered into the Finnish Register of Occupational Diseases because of an occupational disease in from 1988 to 1999. Those reported to have occupational rhinitis (n = 3,637) were compared with those reported to have an occupational disease other than occupational rhinitis, asthma, allergic alveolitis, or allergic contact dermatitis (n = 31,457). The term reference population is hereafter used to for the latter group. The reference population was selected from the same register as the rhinitis patients in order to represent the same source population and to be comparable with respect to information concerning the start of follow-up and occupation. At the start of follow-up, those patients with occupational rhinitis were between the ages of 15 and 64 years (mean, 37.7 years), and those in the reference population were between the ages of 15 and 64 years (mean, 41.5 years). Of those in the reference population, 50% had been identified to the Finnish Register of Occupational Diseases as a result of a repetitive strain injury, with 19% having noise-induced hearing loss, 13% having irritant contact dermatitis, 8% having an asbestos-related disease, and 10% having experienced some other occupational disease. Table 1 presents the distribution of occupational rhinitis patients and the main causative agents by occupation.

In Finland, all employees must be insured against occupational diseases and accidents at work. Since 1982, the insurance also covers farmers, regardless of their professional status. The compensation for a confirmed occupational disease is relatively generous. It includes the costs of treatment, retraining, or reeducation, and various allowances and pensions for an accepted occupational disease. The costs of medical examinations for a suspected occupational disease also are paid regardless of the final decision. The insurance also covers students in vocational training. In Finland, occupational rhinitis is diagnosed in central hospitals or at the Finnish Institute of Occupational Health. The diagnosis necessitates work-related symptoms, sensitization to a specific agent at work, a positive nasal challenge test to this agent, and the exclusion of other reasons for rhinitis.

Follow-up
Through the use of their unique personal identification codes, the patients were observed for asthma incidence in two national registries (ie, the Medication Reimbursement Register of the Social Insurance Institution of Finland and the Finnish Register of Occupational Diseases). Duplicate notifications between the registers were identified using the patients’ personal identification codes. The vital status of the patients on December 31, 2000, was verified from the Population Register Center. The follow-up ended at the occurrence of asthma or death or on December 31, 2000, whichever occurred first. The study protocol was approved by the ethics committees of the participating institutions.

There were 21,739 person-years of follow-up for those with occupational rhinitis (average duration of follow-up, 6.0 years) and 241,145 person-years for the reference population (average duration of follow-up, 7.7 years). Originally, 229 persons (6%) with occupational rhinitis and 1,045 persons (3%) in the reference population were found to have asthma already before the notification of the occupational disease. In addition, 1,246 patients were notified at the same time for both occupational rhinitis and occupational asthma. These persons were not included in the study.

Definition and Ascertainment of Cases
In Finland, asthma patients are reimbursed for their medication at a higher than normal level. To receive the compensation, the patients must apply to the Social Insurance Institution and provide a medical certificate written by a chest physician (for children, a pediatrician). The disease must fulfill the diagnostic and severity criteria of asthma, objective data of reversible bronchial obstruction must be available, and the pattern of disease must be typical and persistent.⁶ National health insurance, which includes a drug reimbursement system, covers the entire population, and consequently almost all Finnish patients with asthma who fulfill the criteria are identifiable in the register. The only exception concerns patients with recognized occupational asthma, who receive full compensation for medication from the Statutory Accident Insurance. The latter group of patients is centrally registered by the Finnish Register of Occupational Diseases. The recognition of occupational asthma necessitates a diagnosis of asthma by a chest physician and individual evidence of a causal association between a specific workplace exposure and the disease.⁷

A patient was defined as having a case of asthma if he or she received the right for reimbursement of asthma medication from the Social Insurance Institution or was entered into the Finnish Register of Occupational Diseases because of recognized occupational asthma. The date of the application for the reimbursement right of medication costs or the date of the notification report to the Finnish Register of Occupational Diseases was used as the date of diagnosis.

Among those with special reimbursement rights for asthma medication, the reliability of the asthma diagnosis is high. In a random sample of working-aged asthmatic patients with granted reimbursement rights, asthma had been clinically established for 99%.⁶

Statistical Analysis
The incidence rates of asthma were calculated by dividing the number of cases by the accumulated number of person-years. The incidence rate ratios (hereafter referred to as RRs) of asthma for those with occupational rhinitis in comparison with the reference population were estimated using a log-linear model. Gender, age at notification of rhinitis (15 to 24 years, 25 to 34 years, 35 to 44 years, 45 to 54 years, and 55 to 64 years), and occupation at the time of the occupational disease notification (ie, farmer, animal husbandry worker, textile worker, electrical worker, wood worker, baker, cook, hairdresser, cleaner, other manufacturing or service worker, and other worker) were included in the model. Interactions between the variables were tested. The interaction between the rhinitis effect and occupation (p < 0.001) and that between age and gender (p = 0.01) were significant, and they were included in the final model.

Time-to-event methods⁸ were used to analyze the time from the notification of occupational rhinitis (or reference disease) to the time of the diagnosis of asthma. A life-table estimator of hazard function was used to assess the differences in the rates of asthma according to the rate differences between those with occupational rhinitis and the reference population. Appropriate computer software (SAS; SAS Institute, Cary, NC) was used for the statistical analyses.

We performed separate analyses that were restricted to a follow-up ending at the age of 65 years. Eighty-five patients with rhinitis (2%) and 3,216 persons in the reference population (10%) were affected by this restriction. The results of this analysis were similar to those for the entire follow-up and, therefore, have not been presented.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Of the 3,637 patients with occupational rhinitis, 420 (11.6%) received diagnoses of asthma during the follow-up period compared with 972 diagnoses of asthma (3.1%) among the 31,457 persons in the reference population. The crude incidence rate of asthma was 19 per 1,000 population per year for those with occupational rhinitis and 4.0 per 1,000 population per year for the reference population. When only those persons with occupational rhinitis that had been accepted by the insurance system were considered, 300 of 2,295 patients (13.1%) received diagnoses of asthma during the follow-up period. The crude RR for asthma was 4.8 (95% confidence interval [CI], 4.3 to 5.4) for all patients notified as having occupational rhinitis, 5.4 (95% CI, 4.8 to 6.2) for those accepted as having occupational rhinitis, and 3.7 (95% CI, 3.1 to 4.5) for those with occupational rhinitis that had not been accepted for compensation.

There was a significant interaction between occupation and the rhinitis-associated risk of asthma (p < 0.001) [ie, the RR for asthma among patients with occupational rhinitis differed across occupations when the patients with rhinitis in a given occupation were compared with patients in the same occupation in the reference population]. The adjusted RR for asthma among the patients with rhinitis was the highest for those employed as farmers or as wood workers at the time of the rhinitis notification (Table 2 ). Among the farmers, animal husbandry workers, and bakers, the numbers of cases were sufficient for a comparison between those with accepted occupational rhinitis and the rest. Among the farmers, the RR was 6.9 (95% CI, 5.6 to 8.5) for those with occupational rhinitis whose conditions had been accepted for compensation and 6.1 (95% CI, 4.2 to 8.3) for those with occupational rhinitis whose conditions had not been accepted for compensation, among the bakers the RR was 2.6 (95% CI 1.3 to 5.4) for those with occupational rhinitis whose conditions had been accepted for compensation and 2.5 (95% CI, 1.1 to 5.6) for those with occupational rhinitis whose conditions had not been accepted for compensation, and among the animal husbandry workers the RR was 2.6 (95% CI, 1.3 to 5.1) for those with accepted occupational rhinitis and 6.9 (95% CI, 3.7 to 12.2) for those with unaccepted occupational rhinitis. There was a significant interaction between age and gender (p = 0.01), the RR being 1.8 (95% CI, 1.1 to 3.0) for the women in comparison with the men among those aged 15 to 24 years, but decreasing thereafter with increasing age so that in the 55- to 64-year-old age group there was no difference in the risk between women and men (RR, 0.9; 95% CI, 0.7 to 1.2). The interaction term was included in the model.

View larger version (10K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Hazard function estimates of asthma according to the time since the start of follow-up for the patients with occupational rhinitis and for the reference population.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

Further difficulties for the interpretation of the results were caused by the problems of defining the exact time of onset for both rhinitis and asthma. Patients referred to a Canadian occupational asthma clinic reported that their asthma symptoms had begun an average of 5 years before they were referred to the clinic and symptoms of rhinitis had preceded the asthma symptoms for about half of them.⁵ In a Finnish study, hairdressers with occupational rhinitis had experienced symptoms of rhinitis an average of 4.6 years before they were diagnosed with occupational rhinitis⁹ and patients with isocyanate-induced asthma had experienced asthma symptoms 2–4 years before the diagnosis of asthma was made.¹⁰ Among our patients, the risk of asthma was especially high during the year following notification. It is likely that many of the patients underwent clinical examinations concurrently for both asthma and rhinitis, and the exact date of occurrence of an established disease in each of the registers is influenced by various nonbiological factors. For example, the symptoms of rhinitis may not have prompted any further examinations until the first symptoms of lower airway obstruction or hyperresponsiveness appeared. According to our experience, this priority of clinical examinations is not uncommon and would have led first to a diagnosis of occupational rhinitis and soon thereafter to a diagnosis of asthma. Nevertheless, there also may be biologically plausible reasons for a relatively short interval between the occurrence of the two conditions, and we did not want to systematically exclude cases of asthma that had been registered soon after the notification of occupational rhinitis. It is also noteworthy that exclusion from follow-up due to the fact that asthma had already been registered was twice as common among the patients with occupational rhinitis as in the reference population. Yet, there was still an increased incidence of asthma among the patients with occupational rhinitis even several years after the notification of rhinitis. This trend is very unlikely to have been notably influenced by any systematic bias inherent in the timing of the onset of disease for patients with asthma or rhinitis. Moreover, even in the reference population, the incidence of asthma seemed to be slightly higher soon after the notification of the occupational disease than during the later years of follow-up. This finding probably indicates that clinical investigations for an occupational disease also may have prompted investigations for asthma.

Among the animal husbandry workers and farmers, the distribution of agents causing rhinitis was similar. In Finland, the main difference between these occupations is that animal husbandry workers are municipal, salaried workers while farmers are self-employed. Despite the common work characteristics, the animal husbandry workers with rhinitis that had been recognized as an occupational disease by the insurance system had a lower risk of asthma than did those without such recognition. On the other hand, there was no difference in the recognition of rhinitis among the farmers, and their risk was similar to that of animal husbandry workers whose occupational rhinitis had not been recognized for compensation. This finding may indirectly indicate that, among the animal husbandry workers, the recognition of occupational rhinitis triggered some effective preventive measures, while such measures were not taken for (self-employed) farmers. The practice of dealing with recognized cases of occupational rhinitis in Finland has not been described systematically. According to our experience, rhinitis usually is considered to be a mild disease, and job retraining is usually an option only when occupational rhinitis is accompanied by bronchial hyperresponsiveness, the worker is young, and the possibility of avoiding further exposure with the current employer is poor (eg, in bakeries). For older workers, or in larger companies, some other preventive measures are recommended. Yet, the implementation of such measures has not been systematically surveyed. The results indicate that more could probably be done to prevent asthma among these patients.

More than 200 agents have been established as causes of occupational asthma,¹¹ and numerous studies^{6 12 13} have indicated that work-related factors account for 10% of cases of adult-onset asthma. Nevertheless, there is a long way to go from such studies to the primary prevention of work-related asthma based on industrial hygiene limit values or other general measures affecting an important fraction of the workforce. Meanwhile, it is likely that preventive efforts could be successfully targeted by identifying high-risk individuals and tailoring intervention programs to them. Our register-based results indicate that patients with occupational rhinitis should be considered as a potential risk group in such efforts. Further studies, collecting more detailed information, should assess the impact of individual interventions. Such studies probably could be undertaken among historical cohorts of patients with occupational rhinitis and also prospectively among patients with newly diagnosed occupational rhinitis.

	Acknowledgements

 
We are indebted to Kari Toivola and Timo Pitkonen of the Finnish Social Insurance Institution, and to Ilpo Mäkinen and Anja Saalo of the Finnish Register of Occupational Diseases for their assistance in building the data files. We thank Ms. Georgianna Oja for the linguistic revision of the manuscript.

	Footnotes

 
Abbreviations: CI = confidence interval; RR = relative risk

The study was financially supported by a grant from the Ministry of Social Affairs and Health, Department for Promotion of Welfare and Health.

Received for publication December 21, 2001. Accepted for publication June 16, 2002.

	References

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