Body Mass Index in Relation to Adult Asthma among 135,000 Norwegian Men and Women

Wenche Nystad , Haakon E. Meyer, Per Nafstad, Aage Tverdal and Anders Engeland

From the Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

Received for publication January 14, 2004; accepted for publication June 3, 2004.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The authors estimated the association between asthma and body mass index in a 1963–2002 study of 135,000 Norwegians aged 14–60 years who were followed on average for 21 years. Cox proportional hazards regression models were fitted to estimate the relative risk of asthma adjusting for smoking, education, and physical activity. Compared with persons with a body mass index (weight (kg)/height (m)2) of less than 25, overweight (body mass index: 25–29) men and women had relative risks of asthma of 1.27 (95% confidence interval (CI): 1.13, 1.43) and 1.30 (95% CI: 1.17, 1.45), respectively, while obese (body mass index: ≥30) men and women had relative risks of 1.78 (95% CI: 1.35, 2.34) and 1.99 (95% CI: 1.67, 2.37), respectively. Stratified analyses revealed a similar association between body mass index and asthma for never smokers, ever smokers, persons with less than or equal to 12 years of education, and persons with more than 12 years of education. Analyses including all the covariates gave results similar to those not adjusting for these factors. The risk of asthma increased steadily with body mass index, from a body mass index of 20 in men and of 22 in women. In men, the risk of asthma increased by 10% with each unit of increased body mass index between 25 and 30. The similar value for women was 7%. Overweight or obese persons reported asthma more often than did thinner persons after adjustment for smoking, education, and physical activity.

asthma; body mass index; cohort studies; obesity

Abbreviations: Abbreviation: CI, confidence interval.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Studies have suggested that obesity is a risk factor for adult asthma (15). Most of these studies have been cross-sectional. However, having asthma may lead to a sedentary lifestyle with increased risk of developing obesity. Associations between obesity and asthma should thus be addressed in longitudinal studies ensuring that obesity develops before asthma. Few studies have explored the relation between body weight and adult asthma prospectively (2, 3, 6). The follow-up periods have been short, information on important covariates and/or potential confounders has been inadequate, and measures of height and weight have been mainly self-reported. Some studies have found a relation between asthma and obesity in females but not in males (2, 3). The association between body mass index and asthma should be explored further in studies with a longitudinal design and with sufficient statistical power to ascertain potential confounding.

During the 1960s and 1970s, a large proportion of the Norwegian population took part in health surveys (7, 8). These surveys included measures of height and weight. A total of 135,000 of these participants have also taken part in more recent health surveys, which also have collected information on asthma. Linking information from the different surveys gave us the opportunity to explore the association between body mass index and adult asthma prospectively in a large cohort of Norwegians.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Between 1963 and 1999, 1.8 million Norwegians aged 14–59 years participated in different population-based, government-run health surveys that included height and weight measurements. Participation rates varied between 75 percent and 90 percent. Since 1994, health surveys have also collected information on asthma and, at the end of 2002, a total of 320,333 persons had participated in these latter surveys. The combined cohort has been described in more detail elsewhere (9, 10). Briefly, a major part of the health surveys in the period 1963–1975 was included in a nationwide screening program aimed at detecting tuberculosis (8). This screening was compulsory for all Norwegians aged 15 years and above. The main objective of most of the other studies was to assess risk factors for coronary heart disease, but items of other exposures and health outcomes were also included (7, 11).

The current study population includes participants from the health surveys with information on asthma who also have had their height and weight measured in a previous population-based, government-run health survey. Inclusion criteria were as follows: 1) answered questions on asthma in 1994–2002 before the age of 80 years, 2) height and weight measured in a health survey prior to the survey where they answered questions on asthma, 3) height and weight measured at ages 14–59 years, and 4) height and weight measured before the development of asthma.

Altogether, 135,405 persons fulfilled the inclusion criteria. These persons were first measured, and then they participated in a health survey and answered questions on asthma. A subcohort of 30,799 persons also answered a question about their usual leisure-time activity. The observation time in the study was defined as the time from the date of measurement of height and weight until the presence of asthma, age 60 years, or the date of answering questions on asthma.

Variables
Asthma
Information on asthma and the onset of asthma in this study was based on the following questions in a self-administered questionnaire: 1) Have you ever had asthma? 2) If yes, at what age did you get asthma for the first time?

Body mass index
Height and weight were measured in a standardized way by a trained staff. Height was measured without shoes, and weight was measured with the subject wearing light clothing. About 3.5 percent of the measurements were excluded because of irregularities (persons wearing shoes, being pregnant, being disabled, and so on).

Height was categorized according to percentiles in a US reference population (12, 13). For ages 14–20 years, the categories were as follows: less than 25th (low), 25th–74th (medium), 75th–94th (high), and greater than or equal to 95th (very high). Above the age of 20 years, the categories were defined by the boundaries defined by the above percentiles at age 20 years.

Body mass index (weight (kg)/height (m)2) was categorized into less than 25.0 (normal weight), 25.0–29.9 (overweight), and 30.0 or more (obese). For ages 14–18 years, growth curves linked to the same adult body mass index categories were used (14).

Covariates
The study subjects were divided into never smokers and ever smokers and into those having 12 years of education or less and those having 13 or more years of education. This information was collected when the persons answered questions on asthma. The study subjects were divided by age at measurement (14–16, 17–19, 20–24, ..., 45–49, and 50–59 years) and year of birth (1910–1919, 1920–1929, ..., 1950–1959, ≥1960).

A question with four alternatives was used to describe level of physical activity: sedentary (reading, watching television, or other sedentary activity); moderate (walking, bicycling, or moving around in other ways at least 4 hours a week); intermediate (participating in recreational athletics, heavy garden work, and so on, at least 4 hours a week); and intensive (participating in hard training or athletic competitions, regularly and several times a week) (15).

Data linkage
As a result of the unique 11-digit identification number assigned to all individuals living in Norway, it was possible to link the height and weight measurements with the person’s answers on questions about asthma.

Statistical analysis
Cox proportional hazards regression models with time since measurement as the time variable were fitted to estimate the hazard rate ratio, hereafter denoted relative risk, of asthma. These analyses were performed with the SPSS statistical program (16). The results were presented as the relative risk of asthma with 95 percent confidence intervals.

The hazard function of asthma by body mass index in the Cox model was estimated by using penalized spline functions in S-PLUS statistical software (17) with 6 df. Body mass index values from ages less than 18 years were transferred to predicted body mass index values at age 18 years using growth curves (14).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
A total of 135,405 persons aged 14–59 years (mean age: 28 years) at height and weight measurements were included in the present study (table 1). The participants were followed for an average of 21 years (range: 0–39 years) constituting 2,802,227 person-years, and they answered questions on asthma at a mean age of 52 years. A total of 4,218 persons developed asthma at age 15–60 years (mean age at onset: 41 years; mean time from measurements of height and weight to the onset of asthma: 15 years).


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TABLE 1. Number of observed person-years and cases of asthma in a study of the association of body mass index and asthma, Norway, 1963–2002
 
The proportion of overweight or obese (body mass index: ≥25) individuals at the start of the observation time was 26 percent and 21 percent in men and women, respectively. Compared with persons with a body mass index below 25, overweight men and women had relative risks of asthma of 1.27 (95 percent confidence interval (CI): 1.13, 1.43) and 1.30 (95 percent CI: 1.17, 1.45), respectively, while obese men and women had relative risks of 1.78 (95 percent CI: 1.35, 2.34) and 1.99 (95 percent CI: 1.67, 2.37), respectively (table 2). By including height in the analyses, we found that there was a somewhat higher risk of asthma in the shortest persons.


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TABLE 2. Relative risk of asthma with 95% confidence intervals obtained from a Cox regression analysis including age at measurement, year of birth, and either body mass index or height, Norway, 1963–2002
 
Stratified analyses revealed a similar association between body mass index and asthma for never smokers and ever smokers (table 3). For persons with 12 years of education or less and persons with more than 12 years of education, a similar association was observed. There were fewer persons with information on physical activity. In analyses stratified by level of physical activity, overweight and obese persons tended to have a higher risk of asthma in all strata except among men with an intensive physical activity level.


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TABLE 3. Relative risk of asthma with 95% confidence intervals obtained from a Cox regression analysis including age at measurement, year of birth, and body mass index in subgroups, Norway, 1963–2002
 
Since the date of diagnosis was uncertain and a diagnosis of asthma might influence body mass index, analyses were also performed with start of follow-up 5 years after measurement of body mass index. The results were similar (data not shown). Furthermore, analyses were performed to reveal possible changes due to diagnostic changes or increased awareness of asthma over time. Inclusion of only those who were at least 18 years at measurement or inclusion of only persons born before 1950 also gave very similar results (data not shown).

To deal with possible misclassification of chronic obstructive pulmonary disease, we also performed analyses including only persons aged 40 years or less, and we did stratified analyses on smokers and nonsmokers, which produced similar results.

Finally, an analysis including physical activity, education, and smoking in addition to body mass index gave very similar results as the analysis not adjusting for these factors regarding the association between body mass index and asthma (table 4). This final analysis included 17,619 men and 12,408 women with complete information. Of these, 385 men and 436 women developed asthma at ages 15–60 years (mean age at onset: 47 years).


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TABLE 4. Relative risk of asthma with 95 percent confidence intervals obtained from a Cox regression analysis adjusting for age at measurement and year of birth in addition to the variables listed below, Norway, 1963–2002
 
The association between body mass index and asthma was also explored in detail using penalized spline functions (figures 1 and 2). The incidence of asthma increased steadily with body mass index after a body mass index of 20 in men and of 22 in women. Furthermore, in men, the risk of asthma increased by 10 percent (95 percent CI: 2, 18) with each unit of increased body mass index between 25 and 30. The similar figure for women was 7 percent (95 percent CI: 0, 14).



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FIGURE 1. Logarithm of the relative risk of asthma by body mass index (BMI) for men, using a Cox model estimated with a penalized spline function in S-PLUS statistical software, with 6 df, adjusted for birth year and age at measurement, Norway, 1963–2002.

 


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FIGURE 2. Logarithm of the relative risk of asthma by body mass index (BMI) for women, using a Cox model estimated with a penalized spline function in S-PLUS statistical software, with 6 df, adjusted for birth year and age at measurement, Norway, 1963–2002.

 
The oldest persons with asthma may have a higher risk of dying compared with persons without. To indicate the impact of this, we performed an analysis including only persons who were less than 60 years of age while answering questions on asthma. Compared with the results in table 2, the results on the association between body mass index and asthma were somewhat strengthened; the overweight persons had a relative risk of 1.39 (95 percent CI: 1.18, 1.63) and 1.43 (95 percent CI: 1.26, 1.62) in men and women, respectively. The corresponding values for obese persons were 1.88 (95 percent CI: 1.28, 2.76) and 2.21 (95 percent CI: 1.75, 2.80) in men and women, respectively. Furthermore, cardiovascular disease could also cause symptoms suggestive of bronchial asthma (18). Stratified analysis including only persons without any cardiovascular disease and diabetes (n = 107,000) revealed, however, similar results (data not shown).


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In this longitudinal study of 135,000 Norwegian men and women, we found that overweight and obese persons had an increased risk of adult asthma. This finding was consistent across different strata of smoking, education, and physical activity. In contrast to other studies, our study showed similar results for men and women. The risk of asthma increased steadily from a body mass index of 20 in men and of 22 in women.

Obesity has many negative health consequences (19). Our findings support the hypothesis that obesity is a risk factor for adult asthma. Few prospective studies have explored the association between adult asthma and obesity, adjusting for potential confounders (1, 3, 6). The first adult study with a longitudinal perspective was the US Nurses’ Health Study (20). That study, including women aged 24–46 years with self-reported body mass index with 4 years of follow-up, found a positive association between body mass index and asthma. We found an increased risk in both sexes. In contrast, Beckett et al. (1) found that gain in body mass index increased the risk of asthma in females but not in males. However, as underlined by Chinn (20) in a recent review, the separate analyses for men and women were not shown. Chen et al. (3) reported that obesity increased the risk of asthma in women but not in men. That study was also based on self-reported body mass index in a 2-year follow-up.

Our study is not a regular cohort study. We have, however, measurements of body mass index among persons taking part in health screenings with a diagnosis of asthma after measurement of height and weight. Consequently, we have a longitudinal study, where the exposure variable is measured independently of the self-report of asthma. We thus have included individuals in the present study from the date of body mass index measurement and followed them until they reported asthma, including the age at onset, or until our defined end of follow-up.

One important dimension of our study is that the study is based on standardized measures of body mass index. The validity of self-reported height and weight has been shown to vary systematically with body mass index (21, 22). Furthermore, our questions on asthma have been used in other Norwegian population-based studies of asthma in children and adults (23). Questionnaire-based information on asthma and physician diagnosis of asthma in Norwegian population-based studies of asthma tend to give similar results (24).

One important issue in our study is whether the self-reported age at onset of asthma might be uncertain. We thus performed additional analyses with the start of follow-up 5 years after the body mass index measurements, which did not influence the results. Furthermore, almost 500 individuals answered the health survey twice (most of these after the measurements of height and weight), including age at onset. In 24 percent of the asthma cases, there was no difference in reported age at onset and, in 45 percent of the cases, age at onset varied by less than 5 years. A concern might also be if there was a misclassification of chronic obstructive pulmonary disease. Analyses restricted to persons less than 40 years of age and among smokers and nonsmokers, however, offer support that the findings in the present study are not biased by misclassification of chronic obstructive pulmonary disease.

Another aspect is whether adults with new onset of asthma actually are incident asthma rather than cases of the disease that has relapsed after a symptom-free period. Adults with childhood asthma, with symptom-free periods during adolescence, may have an increased risk to develop obesity-associated asthma later in life compared with adults without childhood asthma because of a sedentary lifestyle. We cannot exclude that this might have influenced our results.

The prevalence of asthma is low in our study because we include only incident asthma cases, which do not represent the lifetime prevalence of asthma in the general population. The strengths of our study are the large number of persons included and recruited from the general population and the long observation period.

Information on education and smoking from the last survey was used, that is, after an eventual diagnosis of asthma. However, since the mean age at diagnosis was 41 years and 90 percent of the cases were at least 30 years at onset, education was probably completed, and those smoking had probably started smoking prior to onset. Additional analyses including only persons aged less than 60 years also suggested that the association between body mass index and asthma in our study might be stronger than in the main analysis in the present study.

Our analyses applying a spline function revealed that using the standardized categories of body mass index in relation to the definition of overweight (body mass index: ≥25) and obesity (body mass index: ≥30) is not necessarily the optimal way of exploring the association between asthma and body mass index. Furthermore, we show how the risk of asthma increases in the population with each unit of increased body mass index. The associations seen in this study add insight to the relation between obesity and asthma.

The causal links between asthma and obesity need to be further examined with a longitudinal design, including secondary asthma phenotypes and the life course of obesity. However, the present study found that overweight or obese men and women report asthma more often than do thinner persons, even after adjustment from smoking, education, and physical activity.


    ACKNOWLEDGMENTS
 
The authors are grateful to those who during almost 40 years have collected the data used in the present study. These are persons connected to the former National Health Screening Service, the Nord-Trøndelag Health Survey (HUNT), the Hordaland Health Survey (HUSK), and the Tromsø Study.


    NOTES
 
Correspondence to Dr. Wenche Nystad, Division of Epidemiology, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway (e-mail: wenche.nystad{at}fhi.no). Back


    REFERENCES
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 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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