a Department of Hygiene, Hamamatsu University School of Medicine, Japan.
b Clinical Trials Research Unit, University of Auckland, New Zealand.
c Department of Otorhinolaryngology, Nagoya University School of Medicine, Japan.
d Department of Otorhinolaryngology, Hamamatsu University School of Medicine, Japan.
e Department of Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
f Koza Public Health Centre, Japan.
g Kyoto University Health Service, Japan.
h Department of Public Health, Wakayama Medical College, Japan.
i Department of Preventive Medicine, Nagoya University School of Medicine, Japan.
Mieko Nakamura, Department of Hygiene, Hamamatsu University School of Medicine, 1-20-1 Handayama Hamamatsu, 431-3192 Japan. E-mail: miekons{at}hama-med.ac.jp
Abstract
Background One of the proposed aetiological mechanisms for idiopathic sudden deafness is vascular disease. However, it is not known whether traditional cardiovascular risk factors, such as particular dietary factors, are associated with this condition.
Methods A case-control study using pooled controls was conducted in Japan to investigate the relationship between idiopathic sudden deafness and diet. An m:n matched-pairs method was used to obtain age-, gender- and residential district-matched controls from a nationwide database of pooled controls. Food intake was assessed from a self-administered usual food frequency questionnaire that asked about intake of 35 foods (including four drinks). Participants were classified according to the frequency of intake of Western foods and the frequency of intake of traditional Japanese foods. Subgroup analyses were performed using audiometric subtypes of idiopathic sudden deafness.
Results Data were obtained for 164 cases and 20 313 controls. An increased risk of sudden deafness was observed among participants who frequently consumed Western foods (OR = 1.82, 95% CI : 1.142.89), and a decreased risk of this condition was observed among participants who frequently consumed Japanese foods (OR = 0.52, 95% CI : 0.330.82). A direct association of sudden deafness with Western food intake was evident for flat-type hearing loss.
Conclusions This study suggests that a largely Western diet might be a risk factor for idiopathic sudden deafness, a traditional Japanese diet might be a preventive factor for this condition, or both. These findings are consistent with the hypothesis that vascular factors are an important cause of idiopathic sudden deafness, although the possibility of residual confounding by unmeasured confounders such as socioeconomic status cannot be ruled out.
KEY MESSAGES
Keywords Sudden deafness, diet, Japan, case-control study, audiometry
Accepted 20 October 2000
Sudden deafness sometimes has an identifiable cause, but in more than four-fifths of cases the cause is unknown (idiopathic sudden deafness).1 The most plausible mechanisms that have been proposed for this condition include vascular impairment, viral infection and membrane breaks in the inner ear.2 The vascular hypothesis is plausible because the cochlea is a highly vascularized organ supplied by a single artery.3 If idiopathic sudden deafness is caused by vascular disease, it would be reasonable to expect this condition to have similar risk factors to conditions that are known to be caused by vascular disease, such as coronary heart disease or stroke. However, there appear to be few epidemiological data about relationships between traditional cardiovascular risk factors, such as dietary factors and tobacco smoking, and risks of idiopathic sudden deafness.4
There is much evidence that the diet of Japanese people is at least partly responsible for the lower rates of coronary heart disease in Japan than in Western countries.5,6 For example, the traditional Japanese diet is thought to have important anti-atherosclerotic and anti-thrombotic properties.6,7 However, not all Japanese people eat a traditional Japanese dietindeed, a large proportion now eat many kinds of Western foods.8 It is therefore plausible that people in Japan who eat a mainly Western diet would have higher risks of idiopathic sudden deafness than those who eat a traditional Japanese diet. However, the epidemiological evidence concerning this hypothesis is very limited. We accordingly conducted a nationwide case-control study in Japan to investigate this hypothesis.
Methods
Cases
The cases were consecutive patients diagnosed with idiopathic sudden deafness between October 1996 and August 1998 at 17 collaborating public and private hospitals throughout Japan, and who had an audiogram within 14 days of onset of this condition. All cases were recruited prospectively. Idiopathic sudden deafness was diagnosed strictly according to criteria established by Japan's Sudden Deafness Research Committee.9 The key features of these criteria are: (1) sensorineural hearing loss of sudden onset; (2) no involvement of cranial nerves other than the eighth nerve; and (3) no known aetiology (e.g. no known infection or exposure to loud noise).
The pattern of hearing loss in the cases was investigated by audiogram, with readings performed at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz and 8 kHz.10 As there is no internationally standardized classification of sudden deafness subgroups, we used a modified version of Nakashima's classification.11 Nakashima's classification specifies the following subgroups: high-frequency hearing loss (in which the difference between the average hearing losses at 4 kHz and 8 kHz exceeds those at 250 Hz and 500 Hz by 30 dB); low-frequency hearing loss (in which the difference between the average hearing losses at 250 Hz and 500 Hz exceeds those at 4 kHz and 8 kHz by
30 dB); flat-type hearing loss (in which there is approximately equal hearing loss at each frequency); profound hearing loss (in which there is scaling-out,11i.e. no response from the patient at the audiometer's maximum intensityat two or more frequencies); and other hearing loss. Using a minimal difference of 30 dB to define high- and low-frequency hear-ing loss can lead to a large proportion of patients with hearing loss being classified as having other hearing loss,11 and so we used a minimal difference of 20 dB to define these two groups.
Controls
The controls were selected from a database of pooled controls that is maintained by Japan's Research Committee on the Epidemiology of Intractable Diseases. This database contains information about a wide range of lifestyle risk factors for 73 861 men and women throughout Japan aged between 20 and 79 years at the time of control recruitment. The information in the database was obtained by questionnaire surveys conducted between 1987 and 1994. Further details about the database are described elsewhere.12
Controls were matched to cases on age (in 5-year bands), gender, and residential district.13,14 For each case, every available control in the population of pooled controls was selectedin other words, the method of m:n matched-pairs matching was used instead of the conventional 1:n matched-pairs method (which uses a pre-specified number of controls for each case). Further details about the m:n matched-pairs method can be found elsewhere.14,15
Questionnaire
Information on both cases and controls was obtained from a self-administered questionnaire.13 The questionnaire was identical for cases and controls, and included a simple food frequency questionnaire about usual intake of 31 foods and four drinks (hereafter also referred to as foods) during the year before onset of sudden deafness (for cases), or during the year before completing the questionnaire (for controls). Participants were divided into three categories of Western food intake (infrequent, moderately frequent and frequent), and three similar categories of Japanese food intake, based on the factor loadings for these respective food intakes derived by factor analysis.
Statistical methods
The statistical analyses were carried out using the SAS statistical package (version 6.12).16 As is appropriate for m:n matching, the proportion of controls at each exposure level was directly standardized for age, gender and residential district using the population of cases as the standard population.14 Odds ratios (OR) and 95% CI were estimated using conditional logistic regression for group matching, where the matching variables were age, gender, and residential district. Additional adjustments for tobacco smoking,4 alcohol intake,4 sleep duration4 and, as appropriate, for either Japanese or Western food intake, were achieved by inclusion of these variables as covariates in the logistic models. Data on other possible confounders were not available. P-values for trend were estimated by conditional logistic regression, with each exposure variable specified as a continuous variable.
Preliminary analyses of these data that were published in two non peer-reviewed reports17,18 suggested that Western foods (in particular, animal products such as beef and cheese) were associated with higher risks of sudden deafness, and that Japanese foods (in particular, plant products such as Chinese cabbage and green tea) were associated with lower risks of this condition. To make the number of highly correlated dietary variables more manageable, we created an index that corresponded to a diet comprising mainly Western foods, and a second index that corresponded to a diet comprising mainly Japanese foods.1921 For this purpose, principal component factor analysis using a maximum likelihood iterative solution was performed on both cases and controls, then the factors were rotated by a varimax method.16 The number of factors was pre-specified as two for the purpose of this analysis. The first factor accounted for 54.9% of the total variance, and the first and second factors accounted for 79.2%. Figure 1 shows the factor loadings for each of the 35 foods. Two main clusters were observed. The first cluster, which had factor loadings for the second factor that were higher than those for the first factor, contained mainly Western foods. The second cluster, which had factor loadings for the first factor that were higher than those for the second factor, contained mainly Japanese foods, such as tempura, tofu and green tea. Two foods that had factor loadings for the second factor that were slightly greater than those for the first factorkamaboko (boiled fish paste) and tsukudani (fish and shellfish boiled in sweetened soy source)were included in the Japanese food cluster on a priori grounds. The Cronbach alpha values were 0.68 for Western foods and 0.78 for Japanese foods. For each participant, a Western food intake score was then calculated by summing the frequencies of intake (scores: lowest frequency of intake = 1, middle or missing = 2 and highest = 3) for each of the foods in the Western food group. Participants were subsequently divided into three groups on the basis of these scores: frequent intake of Western foods (highest quartile), moderate intake of Western foods (middle two quartiles), and infrequent intake of Western foods (lowest quartile). A Japanese food intake score, and Japanese food intake groups, were defined in the same way using Japanese foods. There was little evidence that the Japanese and Western food intake variables had potential for collinearity (Spearman correlation coefficient = 0.28).
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Characteristics of study participants
Of the 171 eligible patients diagnosed with idiopathic sudden deafness at the participating hospitals during the study period, 164 were included as cases in this study. Patients were not included as cases if no age-, gender- and residential district-matched controls could be obtained (n = 4), or if the otorhinolaryngologist (TN) who interpreted the audiograms could not identify which audiogram was for the ear affected by sudden deafness (n = 3). All cases included in these analyses had unilateral sudden deafness. Data were obtained for a total of 20 313 controls.
The characteristics of the cases and controls are shown in Table 1. Controls were on average 3 years older than the cases. Roughly equal proportions of the cases were men and women, but a larger proportion of controls were women (54.6%) than men (45.4%). This difference occurred because the m:n matched-pairs method of control selection does not aim for equal proportions of participants in different categories of matching variables (any resulting imbalances are compensated for in the analytical procedure). The mean hearing thresholds are shown for cases in Table 2
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In this nationwide case-control study with pooled controls, increased risks of idiopathic sudden deafness were observed among participants who frequently consumed Western foods and among participants who infrequently consumed Japanese foods. In addition, a direct association of sudden deafness with Western food intake was evident for flat-type hearing loss, and an inverse association with Japanese food intake was evident for participants with other forms of hearing loss.
Study strengths and weaknesses
A strength of this study was its use of relatively rigorous diagnostic procedures, including strict diagnostic criteria and the interpretation of audiograms by an otorhinolaryngologist who was blinded to participant exposure status. Furthermore, the cases were consecutive, so they are likely to have been reasonably representative of the individuals in Japan who developed this condition during the study period and presented to a hospital (although no actual response rates were obtained). In addition, the age and gender distribution of cases was reasonably similar to the age and gender distribution of individuals with this condition, as observed in a nationwide epidemiological survey.22 With regard to the controls, the pooled case-control study method enabled data from a large number of population-based controls to be obtained cost-efficiently.
Although the number of cases in this study was larger than in the only previous similar study,4 the number was nevertheless quite small. The effect estimates are therefore moderately imprecise, particularly in the subgroup analyses. In addition, the case recruitment period (19961998) differed somewhat from the control recruitment period (19871994). However, the results obtained when the controls were restricted to those recruited toward the end of the control recruitment period (19931994) were very similar to the results reported in this paper (although there was a tendency for the OR to be slightly further from the null). Furthermore, there were only modest changes in food consumption patterns in Japan between these periods.23,24 We are therefore reasonably confident that the controls were adequately representative of the study base (i.e. the source population of cases during the study period), and that the study thereby complied with the study base paradigm for case-control studies.25
The main potential sources of bias in this study were exposure measurement error and confounding. There is no reason to suspect that misreporting of dietary intakes in this study would have differed appreciably in magnitude between cases and controls, particularly because most of the cases would not have had any prior knowledge of the hypotheses being investigated in this study. Errors in measurement of these exposures are therefore likely to have been mainly non-differential with respect to the outcome, thereby tending to bias the effect estimates towards the null.
This study controlled for several possible confounders, including age, gender and area of residence. However, the possibility remains that confounding by some other factor might have accounted for the observed associations. For example, it is possible that socioeconomic status might have been independently associated with both the exposures of interest and sudden deafness, thereby creating the potential for confounding by this variable. However, the likelihood of confounding by socioeconomic status or other factors is uncertain because of a paucity of information about the relationship between these variables and sudden deafness.
Consistency with published findings
There appears to be only one previous peer-reviewed report4 on the associations of idiopathic sudden deafness with dietary habit. This report arose from a case-control study (109 cases and 109 controls) that was conducted in Japan in the early 1990s. The study showed that, after controlling for age and gender, participants with a high intake of raw vegetables were about half as likely to have been cases as participants with a low intake of these vegetables. Because the Japanese diet is partly characterized by frequent intake of vegetables, this finding is broadly consistent with the findings in the present study.
Interpretation and implications
There are several possible explanations for the associations observed in this study. First, the associations may have been chance findings. This is more likely for the subgroup findings than for the main findings. The confidence intervals for the main effect estimates suggest that the estimates were unlikely to have arisen by chance alone.
Second, the associations may have been produced by systematic errors, including errors in measurement of the exposures or the outcome, selection biases or residual confounding. In this study, outcome measurement error is likely to have been negligible, and exposure measurement errors are likely to have biased the effect estimates toward, rather than away from, the null, thereby tending to produce conservative effect estimates (see above). Furthermore, selection biases should have been small because the cases are likely to have been representative of the cases in the populations at risk that sought hospital treatment, and the controls are likely to have been reasonably representative of the study base, as discussed above. The possibility of confounding by unmeasured confounders, such as socioeconomic status or other cardiovascular risk factors, cannot be discounted.
Third, the observed associations may have been due to reverse causation (e.g. sudden deafness causing frequent intake of Western foods, rather than vice versa). Because this study assessed exposure status among cases after the onset of the outcome, the possibility of reverse causation cannot be ruled out. However, the questionnaire asked about habitual dietary intakes before the onset of the condition, and in addition, it was administered (in most instances) to cases no more than a few weeks after the onset. It appears unlikely, therefore, that sudden deafness would have caused any genuine changes in the dietary intake variables. However, the possibility that sudden deafness produced some change in the reported levels of these variables still remains.
The final possible explanation for the associations observed in this study are that Western foods caused sudden deafness, Japanese foods prevented sudden deafness, or both. These hypotheses are plausible because, for example, there is evidence that a diet rich in saturated fatty acids promotes platelet aggregation26 and factor VII coagulant activity,27 and there is some evidence that accelerated coagulation status could be one of the aetiological mechanisms underlying sudden deafness.28 A Western diet rich in saturated fatty acids might therefore potentially increase the risk of this condition by increasing the coagulability of blood. These findings suggest a need for future epidemiological research studies (which could include case-control studies, case-crossover studies25 or ecological studies) to investigate dietary determinants of idiopathic sudden deafness. Data on levels of possible intermediate factors (e.g. platelet aggregation, blood lipids or blood pressure) in cases could also be potentially useful.
Acknowledgments
This study was supported by grants-in-aid from the Research Committee on the Epidemiology of Intractable Diseases and the Research Committee on Acute Profound Deafness, both under the auspices of the Ministry of Health and Welfare of Japan. The Research Committee on Acute Profound Deafness was responsible for collecting data on the cases in this study. Gary Whitlock contributed to this research during the tenure of a training fellowship from the Health Research Council of New Zealand.
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