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Serum Vitamin C Levels and Use of Health Care Resources for Wheezing Episodes
Arch G. Mainous III, PhD;
William J. Hueston, MD;
Margaret K. Connor, MPH
Arch Fam Med. 2000;9:241-245.
ABSTRACT
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Background Evidence suggests that the antioxidant vitamin C may play a role in lung function and wheezing, although the data are limited to laboratory evaluation of pulmonary function.
Objective To examine the relationship among serum vitamin C levels, wheezing episodes, and use of health care services.
Methods Analysis of adult subjects (aged  17 years) surveyed in the third National Health and Nutrition Examination Survey (1988-1994) (n = 19 760), including measurements of serum vitamin C levels and self-reports of wheezing episodes, ambulatory health care visits, and overnight hospitalizations for wheezing.
Results A large proportion of individuals (2377/19 760 [12.0%]) have received a diagnosis of asthma, chronic bronchitis, or emphysema. Among 874 individuals having an ambulatory visit for wheezing, 408 (46.7%) did not have a diagnosed respiratory condition. Similarly, among 159 individuals hospitalized for wheezing, 61 (38.4%) did not have a diagnosed respiratory condition. Serum vitamin C level had no significant relationship with reported diagnosis of respiratory conditions, episodes of wheezing, or use of health care services for wheezing. In a model computed only with individuals with low or high serum vitamin C levels, after adjustment for potential confounders, no statistically significant relationship was found between serum vitamin C levels and ambulatory care (odds ratio, 0.78; 95% confidence interval, 0.58-1.05) or hospitalization for wheezing episodes (odds ratio, 1.21; 95% confidence interval, 0.67-2.21).
Conclusions Serum vitamin C levels do not appear to be a marker for use of health care services for wheezing. Future investigations of the role of antioxidants in managing respiratory conditions should focus on the clinically important outcomes of health care use.
INTRODUCTION
ASTHMA AND chronic obstructive pulmonary disease are common chronic diseases with significant morbidity and mortality. In the United States, asthma accounts for more than 470 000 hospitalizations annually and more than 5000 deaths.1 Subdivided into chronic bronchitis and emphysema, chronic obstructive pulmonary disease is the fourth leading cause of death of adults in the United States.2
It has been suggested that the recent increase in prevalence of asthma in westernized countries is caused by a change in diet that reduces defenses of the lung against the effects of inhaled irritants and allergens.3-4 Cross-sectional data examining glutathione peroxidase, an integral component of the body's antioxidant system, indicate that levels are reduced in asthmatics compared with control children.5 Several case-control studies have provided supportive evidence suggesting that a diet high in antioxidants may have a beneficial effect on bronchial reactivity.4, 6 These data suggest that antioxidants could play a role in the development and/or severity of asthma.
Vitamin C is an antioxidant that may play an important role in lung function. Evidence from a variety of populations suggests that ascorbic acid (vitamin C) supplementation is associated with improved lung function.7-11 Specifically, ascorbic acid supplementation has been shown to be associated with higher forced expiratory volume in 1 second and forced vital capacity in general populations. In line with this suggestion of a relationship between a deficiency in vitamin C and respiratory function, 2 small (N<120) case-control studies in Africa found lower serum vitamin C levels in asthmatics than nonasthmatics.12-13 Further, another study indicated that serum vitamin C levels were negatively correlated to self-reported wheezing.14
The evidence linking serum vitamin C levels to lung function has been limited to laboratory evaluation of pulmonary function without a clinical correlation. Possible associations between serum vitamin C level and the clinical markers of bronchial function such as asthma exacerbation or wheezing and its potential effect on the use of clinical services, including hospitalization, have not been evaluated. We explored whether serum vitamin C levels are related to episodes of wheezing and differences in use of health care resources for these symptoms.
MATERIALS AND METHODS
DESIGN
This study is an analysis of the third National Health and Nutrition Examination Survey (NHANES III). The NHANES III collected multistage, stratified, clustered samples from a civilian, noninstitutionalized population. The National Center for Health Statistics administered the survey to a randomly selected group of approximately 40 000 residents in 89 communities across the United States. The survey was conducted in 2 phases. The first phase was administered in 44 different locations from October 18, 1988, to October 24, 1991. The second phase took place from September 20, 1991, to October 15, 1994, in 45 different locations. Most surveyed residents (33,994 [86%]) were interviewed in their homes. All surveyed residents were invited to examination centers for additional data collection, including physical examination and laboratory measures. Of those surveyed, 31 311 (79%) completed all or some of the physical examination and laboratory data collection.
To examine the relationship between serum vitamin C levels and manifestations of use of health care services, the following 3 of the 5 NHANES data files were selected for analysis: the household adult data file, examination data file, and laboratory data file. We excluded any person who did not participate in all 3 parts of the survey. All NHANES III public use data files are linked by a common survey participant variable. The variable consistently identifies the same participant in each different data file.
The household adult data file contains the results of the questionnaire administered to all adults in the survey population described above. Adults are defined by the National Center for Health Statistics as any noninstitutionalized civilian aged 17 years or older. During the 6 years of NHANES III data collection, 20 500 adults completed the household survey. The adult interviews were conducted in English and Spanish by highly trained field staff. The staff was continuously retrained throughout the 6-year period to ensure that the appropriate standard was maintained.
The examination and laboratory data files contain the results of the examinations and laboratory tests performed on survey participants who followed up their household interview as requested with a visit to one of the NHANES III mobile examination centers. Survey participants were examined within a month of completing their household interview. A less comprehensive home examination was available to those participants who were unable to leave their homes.
Of those who filled out an adult household survey, 19 760 (96.4%) also completed the laboratory tests and physical examination. These 19 760 survey participants constituted the population for our study. More detailed information on the plan and operation of the NHANES III has been published previously.15
VARIABLES
Independent Variable
Serum vitamin C levels constitute the independent variable for our study and were analyzed as part of the blood chemistry profile created for each survey participant. Serum concentrations of vitamin C were calculated using a fully reduced method of measuring total vitamin C levels by means of high-performance liquid chromatography with electrochemical detection analysis. This method differed from the 2,4-dinitrophenyl hydrazine colorimetric method used in the NHANES II study. Additional information on the laboratory procedures used in the NHANES III are available elsewhere.16
Dependent Variables
Rates of use of ambulatory and inpatient health care services were the outcome measures. The first question relevant to the outcome established whether the survey participant had experienced any "wheezing or whistling in [their] chest at any time in the past 12 months." For those participants who answered positively, 3 additional questions sought to determine the frequency of the wheezing or whistling in the chest and what effect the condition had on the use of health care services. To determine the frequency of the wheezing and/or whistling in the chest, participants were asked, "How many episodes of wheezing or whistling have you had in the past 12 months?" The frequency of episodes in the past year was recorded as a number between 1 and 365 or as "constantly." The participants were then asked 2 questions regarding the use of health care services. The first question accounted for the use of ambulatory services: "During the past 12 months, how many times have you gone to a doctor's office or a hospital emergency room for one of these episodes of wheezing or whistling?" The second question focused on inpatient service: "How many times in the past 12 months were you hospitalized overnight or longer for these episodes of wheezing or whistling?"
Control Variables
In an effort to determine the independent relationship between serum vitamin C levels and use of health care services for wheezing, we included in our analyses a variety of variables that may have some relationship with use of health care services for wheezing. First, we examined whether the subjects had ever received 1 of the following diagnoses that may account for the wheezing episode: asthma, chronic bronchitis, or emphysema. To determine whether there had been any incidence of these conditions, the participants were asked 3 questions concerning what they had been told by a physician. Second, the participants were asked if they were current cigarette smokers, since smoking may irritate respiratory conditions and cause wheezing and thereby increase the use of health care services. Third, standard demographic and socioeconomic status indicators were collected, including total household income in the past 12 months, whether the individual had health insurance (including public and private sources), age, sex, race, and residence in a metropolitan or nonmetropolitan area. Fourth, because of the importance of access to hospital care for asthma and other respiratory conditions, we measured access via the following 2 questions: "Do you have a place where you usually go when you need medical care or advice?" and "Is there one particular person you see at this place?"17
ANALYSIS
Bivariate analyses initially were computed to examine serum vitamin C levels with respiratory diagnoses and use of health care services for wheezing. Logistic regressions were computed on likelihood of ambulatory visits and hospitalizations for wheezing (0 or 1) to examine the independent relationship between serum vitamin C level as a continuous variable and resource use, controlling for race, age, insurance, income, access to care as indicated by having a usual source of care, metropolitan statistical area residence, chronic bronchitis, emphysema, and asthma. Because the potential relationship between serum vitamin C level and use of health care services may be more apparent in individuals who have high or low serum vitamin C levels, 2 additional models were computed using only individuals with serum vitamin C levels categorized as high (75th percentile) or low ( 25th percentile).
We computed our analyses without sampling weights for several reasons. First, previous analyses using NHANES II data linking serum vitamin C levels to respiratory symptoms used unweighted analyses.14 Second, our goal was to maximize internal validity. Thus, we wanted to minimize the amount of data transformation to give us the clearest representation possible of the relationship between serum vitamin C level and use of health care services for wheezing while controlling for subject characteristics.
Unless otherwise indicated, data are given as mean ± SD.
RESULTS
Table 1 indicates that the mean serum vitamin C level for the sample is within the reference range.18 Most of the subjects report access to health care, and a substantial proportion are current cigarette smokers.
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Table 1. Characteristics of 19,760 Subjects
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A large proportion of individuals (2377/19 760 [12.0%]) have received a diagnosis of asthma, chronic bronchitis, or emphysema, as seen in the following tabulation:
The following tabulation shows use of health care services in individuals who reported 1 or more episodes of wheezing in the past 12 months:
Individuals could have received diagnoses of more than 1 of the conditions. Of 17 383 individuals without such a diagnosis, 1759 (10.1%) reported an episode of wheezing. The results indicate that use of health care services for wheezing is a relatively common occurrence, even in patients without self-reported diagnoses of underlying pulmonary disorders. Among 874 individuals having an ambulatory visit for wheezing, 408 (46.7%) did not have diagnosed asthma, chronic bronchitis, or emphysema. Similarly, among 159 individuals hospitalized for wheezing, 61 (38.4%) did not have a self-reported diagnosis of a respiratory condition.
Table 2 indicates that serum vitamin C level has no significant bivariate relationship with reported diagnosis of respiratory conditions or use of health care services for episodes of wheezing. Similarly, the regressions yielded no significant independent relation between serum vitamin C level measured on a continuous scale and use of ambulatory services (P = .52) or hospitalization (P = .10) for wheezing after controlling for relevant variables.
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Table 2. Relationships Between Serum Vitamin C Levels and Respiratory Characteristics
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In the model computed only with individuals with low or high serum vitamin C levels, after adjustment for potential confounders, no statistically significant relationship was found between high and low serum vitamin C levels and ambulatory care (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.58-1.05) or hospitalization for wheezing episodes (OR, 1.21; 95% CI, 0.67-2.21).
COMMENT
The results of this study of greater than 19 000 adults call into question the previously reported relationship of serum vitamin C levels and the diagnosis of asthma.12-13 Moreover, in this cross-sectional design, serum vitamin C level does not seem to be related to recent use of ambulatory health care resources or hospitalization for episodes of wheezing.
Our results may differ from the results of previous studies for several reasons. First, a change occurred between the NHANES II and III in laboratory procedures for measuring vitamin C levels. More importantly, the results from the NHANES II study had a slightly different outcome variable that might suggest a continual problem with wheezing, ie, the question "During the last 12 months, not counting cold or flu, have you frequently had trouble with wheezing?"14 rather than the more episodic outcomes we used (eg, use of health care services for wheezing). The severity of outcome in the NHANES II data, however, was not demonstrated. Use of health care services as measured herein, after controlling for important variables that may influence use of services such as insurance and access to care, seems to be a reasonable proxy for severity of exacerbation, since more severe exacerbations would suggest patient assistance from the health care system.
Second, our results may differ from the previous studies demonstrating lower serum vitamin C levels in asthmatics than nonasthmatics in that the other studies defined asthma as active asthma.12-13 We defined asthma, as well as chronic bronchitis and emphysema, as self-reported physician diagnoses of the condition. It is possible that these diagnoses were not appropriate characterizations of the respondents' current status. However, 10.1% of the individuals who noted wheezing did not report having any of these conditions, and no relationship was found between serum vitamin C level and use of health care services, even when the population was limited to individuals in the highest and lowest vitamin C level quartiles. This finding of undiagnosed respiratory disorders is in line with a previous study in primary care suggesting that 3.3% of adult patients have undiagnosed asthma that was active in the past year.19
Although our results do not support a relationship between serum vitamin C level and use of health care services for wheezing, other data suggest that ascorbic acid supplementation may improve lung function.7-11 These studies have demonstrated an increase in pulmonary function (ie, forced expiratory volume in 1 second and forced vital capacity) with ascorbic acid supplementation in a variety of groups ranging from the general population to workers exposed to high levels of ozone. Because most of the studies determine an independent relationship between ascorbic acid supplementation and pulmonary function via multiple regressions with little discussion of the absolute magnitude of effect, it is unclear whether the demonstrated relationship is clinically important, particularly as it would relate to use of the health care system. One study has yielded results similar to ours that suggest this relationship. That study found that fresh fruit consumption is associated with improved lung function, but they found no difference in serum vitamin C levels between wheezers and nonwheezers.6
Our study has several limitations that may affect the interpretation of the results. First, we assume that serum vitamin C levels should remain generally stable over time, thereby allowing us to examine the relationship between current levels and past use of health care services. This may be inaccurate; however, plasma vitamin C levels are generally stable for months, even during periods of seasonal variation.20 Second, several of the measures are based on self-reports, which may suffer from recall bias. Asthma symptom and health status measures have, however, generally demonstrated reasonably good agreement with clinical measures of pulmonary function.21-22 Third, the NHANES III sample has a higher proportion of smokers than in the general population, which may account for the results.
Our data do not support a relationship between serum vitamin C levels and use of health care services for wheezing. Further study needs to be conducted to determine the impact of ascorbic acid supplementation on use of health care services for respiratory distress.
AUTHOR INFORMATION
Accepted for publication July 9, 1999.
Corresponding author: Arch G. Mainous III, PhD, Department of Family Medicine, Medical University of South Carolina, 295 Calhoun St, PO Box 250192, Charleston, SC 29425 (e-mail: mainouag{at}musc.edu).
From the Department of Family Medicine (Drs Mainous and Hueston and Ms Connor) and the Center for Health Care Research (Dr Mainous), Medical University of South Carolina, Charleston.
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