1 Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
2 Research Unit, University Hospital of the Canary Islands, La Laguna, Spain.
3 Department of Epidemiology, Harvard School of Public Health, Boston, MA.
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ABSTRACT |
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alcohol drinking; alcoholic beverages; cohort studies; common cold; wine
Abbreviations: CI, confidence interval
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INTRODUCTION |
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Despite alcohol's immunosuppressive properties, moderate intake was unexpectedly associated with a decreased risk of common cold among nonsmokers in the only available epidemiologic study known (6). However, this study was conducted on volunteers artificially challenged with rhinovirus; therefore, no prospective data are available on the effect of alcohol consumption on the natural occurrence of common cold. Whether any specific type of alcoholic drink may have a particular benefit is also unknown.
In 19981999, we carried out a follow-up study to address the question of whether alcohol intake has any effect on the risk of developing a common cold episode. We also investigated whether such an effect depends on the type of alcoholic beverage consumed.
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MATERIALS AND METHODS |
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To increase the response rate, all questionnaires were anonymous. To link an initial questionnaire with its corresponding follow-up, we used an eight-digit code formed by the date of birth, gender, and job category (faculty or staff) of each participant. Participants with duplicated codes were excluded from follow-up. The study was approved by the institutional review boards of the five participating universities.
Disease assessment
We provided participants with a calendar and instructed them to record, daily during the duration of what they perceived as a common cold episode, the presence of eight symptoms of common cold and to rate their intensity on a four-level scale from none (0) to very intense (3). These symptoms included runny nose, sneezing, nasal congestion, headache, chills, sore throat, cough, and malaise. Every 10 weeks, we mailed a short questionnaire to participants and asked them to transcribe the information from their calendars so we could update our data on common cold symptoms.
We required three criteria to define a common cold episode: presence of rhinorrhea for at least 3 consecutive days, subjective sensation of having experienced a common cold episode, and a minimum symptom score of 12 out of 24 on the peak day of the episode. We selected the cutoff point of 12 because it maximized the sensitivity and specificity of the common cold diagnosis in a concurrent validation substudy (refer to the information below). However, our main study results did not change substantially when we used other cutoff points.
Exposure assessment
We determined usual alcohol intake by asking subjects about their weekly consumption of red wine, white wine, beer, and spirits during the 12 months before baseline. For each subject, total intake of alcohol per week was calculated as the product of the ethanol content of a drink of average size, as given in the Spanish Health Survey (8) (9.6 g for wine, 9.6 g for beer, and 13.44 g for spirits), and the average number of drinks of red wine, white wine, beer, and spirits consumed per week.
Validation substudy
Concurrently with the main study, we carried out a validation substudy in a random sample of 69 participants. Our goal was to document the validity and reproducibility of common cold diagnosis and alcohol intake.
We compared our diagnoses with those obtained by using the complete diagnosis method of Beare and Reed (9). This method uses a 20-item checklist of common cold symptoms and physical signs; thus, it requires that a physician examine the patient. Each sign and symptom is rated from 0 to 3. Although all items are weighted the same in the original checklist, we assigned them unequal weights based on the relative frequency of symptoms and signs during common cold episodes reported in a large case series (10
). Hence, nasal manifestations contributed 60 percent to the total score compared with 25 percent for lower airways manifestations and 15 percent for general manifestations. A patient was considered to have experienced a common cold episode if his or her score was greater than or equal to 150 points of a total 300 points.
To assess the validity of our measure of usual alcohol intake, we compared our frequency questionnaire with a 12-day diet record. To account for seasonal variation, these 12 days were distributed as 3 days during each season: two nonconsecutive weekdays and one weekend day. To assess reproducibility, we administered the same frequency questionnaire used at the beginning of the study to the 69 participants included in the validation substudy, approximately 1 year later.
Data analysis
Each participant contributed person-time from when he or she returned the initial questionnaire to onset of a common cold episode, termination of the study, or loss to follow-up, whichever occurred first. To take into account the overdispersion due to common cold episodes not being completely independent events, we used negative binomial regression to obtain adjusted incidence rate ratios and their corresponding 95 percent confidence intervals (11). Use of the negative binomial distribution produced broader confidence intervals compared with the Poisson distribution. Secondary analyses in which we did not censor participants after their first common cold episode yielded similar results and are not presented here.
Possible risk factors for common cold considered in the analyses included age, sex, faculty/staff status, university, region, smoking status, contact with children, psychological stress, and vitamin C and zinc intake. Cigarette smoking was assessed by using the standardized World Health Organization questionnaire (12). Smoking status categories were never smoker, former smoker, occasional smoker, and current smoker of 119, 2040, or more than 40 cigarettes a day. Contact with children was measured by three variables: total number of children, number of children less than age 2 years, and number of children who attend kindergarten. Psychological stress was measured by using four independent scales: positive affect, negative affect, stressful events, and perceived stress. Further details on stress assessment have been presented elsewhere (7
). Vitamin C and zinc intake were determined by using a food frequency questionnaire and were validated with 12 daily diet records.
To explore the shape of the curve relating wine consumption to occurrence of common cold episodes, we fitted a model with cubic splines (13) and adjusted for potential confounders. We set three knots at the boundaries of the exposure categories (0, 17, 814, and >14 drinks per week). Other model specifications produced similar curves.
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RESULTS |
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Twenty-seven percent of the participants were teetotalers, and 10 percent drank more than 13 alcoholic drinks of any type per week. Drinkers consumed on average 96 g (standard deviation, 104) of pure alcohol and 3.9 glasses (standard deviation, 5) of wine per week.
Men consumed any alcoholic drink more often than women did. Mean age was higher among moderate-to-heavy wine drinkers compared with teetotalers, but no substantial differences regarding age were found for beer and spirits. Table 1 displays the distribution of sex, age, and other factors by intake of total alcohol and alcoholic beverages.
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Both history of allergic rhinitis and history of any other upper respiratory tract disease were associated with common cold. The incidence rate ratios were 2.7 (95 percent CI: 2.3, 3.2) for history of allergic rhinitis and 3.3 (95 percent CI: 2.7, 4.0) for other upper respiratory tract disease. To reduce the possibility of self-report of bouts of these diseases as common cold episodes, we restricted the analyses to participants who had no history of allergic rhinitis or any other upper respiratory tract disease. The results were similar to those reported above.
Twenty-two percent of the participants were lost to follow-up before the study ended, but the distribution of exposure variables (consumption of red wine, white wine, beer, and spirits) and other factors (sex, age, faculty/staff status) was similar between participants with incomplete follow-up and those with complete follow-up. We also recalculated the incidence rate ratios in two extreme situations. First, we assumed that all subjects lost to follow-up developed a cold within the week after dropping out of the study. Second, we assumed that none of the subjects ever developed a cold. Again, the results were not substantially altered.
The sensitivity of our diagnosis of common cold was 94 percent, and its specificity was 84 percent. The Spearman coefficients of correlation between our alcohol frequency questionnaire and the diet records were 0.76 for wine, 0.72 for beer, 0.59 for spirits, and 0.78 for total alcohol intake. The intraclass correlation coefficients for reproducibility were 0.86 for wine, 0.93 for beer, 0.80 for spirits, and 0.82 for alcohol intake. These results indicate that wine intake is measured with some error. However, this error is likely to occur independently of disease status because our information on exposure was collected before disease occurred. To explore the direction and magnitude of the potential bias due to misclassification of exposure, we reanalyzed the data by entering the variable "wine intake" as dichotomous (abstemious/nonabstemious). The resulting incidence rate ratio was 0.7 (95 percent CI: 0.6, 0.9), which suggests that the true association between wine intake and common cold may be even stronger than the one we observed (nondifferential misclassification of a dichotomous variable).
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DISCUSSION |
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A validation substudy showed that the quality of our measurement of alcohol intake was similar to others reported in the literature (14) and that the diagnosis of common cold was accurate, hence confirming the previous finding that self-diagnosis of common cold is usually correct because the manifestations are typical (15
). The prospective study design ensured that usual alcohol intake was assessed before the diagnosis of common cold was made and thus prevented differential reporting of alcohol consumption between common cold cases and noncases. We also adjusted for known or suspected risk factors for common cold and conducted sensitivity analyses to assess the influence of loss to follow-up, but the results did not change materially. Thus, the inverse association we found is not easily ascribed to confounding, misclassification, or selection bias due to loss to follow-up. Further research may help clarify whether the inverse association between wine intake and common cold can be partially explained by unmeasured variables (e.g., lifestyle habits, drinking patterns).
A protective effect of some nonalcoholic components of wine on the occurrence of common cold is consistent with previous animal and human studies, which showed that some nonalcohol components of wine have strong anti-inflammatory (4, 5
), antioxidant (16
), and vasorelaxant properties (17
). Resveratrol, one nonalcohol component with strong anti-inflammatory activity, is especially abundant in red wine (5
). Therefore, wine consumption may downregulate the immune response that leads to the clinical manifestations of common cold.
In addition, red wine is particularly rich in flavonoids, such as quercetin and catechin (18). Flavonoids are polyphenolic antioxidants whose antiviral properties are mediated by their binding to viral protein and interfering with the synthesis of the viral nucleic acid (19
). Furthermore, specific activity of synthetic flavonoids against rhinovirusesconsidered the major causal agents of the common coldhas been demonstrated in vitro (20
). This finding might explain an increased resistance to viral infection among wine drinkers, but the relevance of any of these or other mechanisms to the relation between wine consumption and common cold episodes remains to be established.
Since the public health burden of common cold results from the disability caused by its clinical manifestations, and the economic costs associated with common cold are due to absenteeism and to the drugs used to alleviate its symptoms, our diagnosis of common cold was a clinical one. Previous studies of risk factors for common cold among artificially infected subjects have sometimes required the presence of symptoms and seropositivity to confirm the diagnosis (6, 21
). These studies found that only one third of subjects exposed to viruses became infected and that only one third of infected subjects developed a clinical cold (22
, 23
). Thus, a diagnosis based on seropositivity would include a high proportion of nonclinically detectable common cold episodes (false positives according to our criteria). In summary, our findings suggest that moderate consumption of wine, but not of other alcoholic beverages, may reduce the incidence of clinical common cold.
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ACKNOWLEDGMENTS |
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The authors thank the following persons who participated in data collection: Drs. Carlos Quintas, Rosa Meijide, Lourdes Maceiras, and Milagros Torres.
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NOTES |
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REFERENCES |
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