Obesity and asthma: cause for concern?

Epidemiology must surely hold the key to discovering the environmental causes of asthma [ 1], but a clear explanation for the epidemic rise in asthma in developed countries over the last 30 years still eludes us. Certainly, changes in the prevalence of known risk factors appear to have played only a small part [ 2] and new aetiological hypotheses are needed. Risk factors for childhood asthma include low birth weight, prematurity and maternal smoking in pregnancy. This suggests that the prenatal environment plays a role in the inception of the disease. However, the prognostic course of childhood asthma is very variable. The disease may be mild or severe and it may either persist into adulthood, remit permanently or remit and later relapse. Furthermore, asthma may develop de novo in adult life. We know little about the determinants of these different patterns of disease but environmental factors in later childhood, adolescence or early adult life may play a part. Such risk factors might add to or modify the effects of the prenatal environment. The role of diet is currently under scrutiny [ 3]. Certainly, diet in developed countries has changed in a number of ways in recent decades. The possible importance of a more sedentary lifestyle has also been discussed [ 4]. In Britain and the USA the rise in asthma in children and adults has been accompanied by an epidemic increase in the prevalence of obesity [ 5–14]. An increasing body of epidemiological evidence suggests that there is an association between fatness and asthma in individuals. Population-based cross-sectional studies of children in the USA and Britain have found positive associations between body mass index (weight/height2) or weight-for-height and wheeze [ 15–17]. Evidence for a positive relation between body mass index (BMI) and reported asthma, however, is conflicting [ 15, 16, 18–20]. This may be because mild asthma tends to be underdiagnosed in fatter children [ 21]. A recent case-control study found that children with moderate and severe asthma were more likely to be overweight than children of normal weight. It also found an association between fatness and severity of asthma symptoms [ 18]. Triceps skinfold thickness is a more sensitive measure of fatness in children [ 22] and was positively associated with wheeze in one study [ 16] but not in another [ 17]. A small clinical study of children without asthma found a positive relationship between triceps skinfold thickness and exercise-induced bronchospasm [ 23]. Population-based data on the relation between fatness and bronchial hyper-responsiveness (BHR) are lacking and new data from Taiwan, reported in this issue, are therefore of interest [ 24]. In the last 20 years the prevalence of asthma in children in Taiwan, as in other parts of south-east Asia, has increased [ 25], in tandem with an increase in obesity. Huang and colleagues investigated the relation of BMI to wheeze and BHR in a cross-sectional study of adolescents. They found that the prevalence of past wheeze rose with increasing BMI in girls, but not in boys, and that the prevalence of BHR was much lower in girls in the lowest quintile of BMI than in other girls. They also observed that BMI was positively associated with atopy and with symptoms of rhinitis in girls. Health surveys of predominantly older adults have found that overweight and obesity, defined by BMI or waist circumference, were associated with a higher prevalence of reported asthma and of symptoms such as wheeze and waking at night with shortness of breath. Fatter individuals were also more likely to report a history of chronic obstructive pulmonary disease, symptoms of chronic bronchitis and shortness of breath on exertion [ 26–29]. However, older adults are not ideal subjects for studying asthma epidemiologically, as it can be difficult in middle-aged and elderly individuals to distinguish symptoms of asthma from those of smoking-related airways disease. Three recent studies have found an association between BMI and asthma in young adults. A study of diet and asthma from Norway observed a positive relation between BMI and asthma symptoms [ 30]. In a nationally representative British birth cohort, BMI was positively associated with the prevalence of asthma and wheeze in individuals studied at 26 years of age [ 31]. In the large Nurses' Health Study II in the USA, a strong positive association between BMI and risk of incident asthma was observed in women aged 27–44 years who were followed over four years [ 32]. This is the first longitudinal study to demonstrate such an association. A biased estimate of the relation between fatness and asthma or wheeze could arise as a result of poor response rates to questionnaires, misclassification of BMI based on self-reported height and weight, or if, amongst people with wheeze, fatter individuals were more likely to report their symptoms. Such bias seems unlikely in the study from Taiwan. Symptom data were obtained from 100% of subjects, height and weight were measured, and the findings for wheeze in girls were supported by those for BHR. One must consider whether the association between fatness and asthma might be explained by confounding factors such as family size. In the latest studies from Taiwan and Britain the associations with BMI persisted after controlling for a number of potential confounders including number of siblings. However, two factors which were not taken into account in these studies were diet and level of physical activity. For example, salt intake, as measured by urinary sodium excretion, is positively correlated with BMI [ 9] and, in men at least, with BHR [ 33]. Studies of diet and asthma which are currently underway may help to clarify whether the relationship between BMI and asthma is explained in part by dietary factors. Low levels of physical activity are a risk factor for obesity and Platts-Mills and colleagues have suggested that reductions in deep breathing associated with a sedentary lifestyle may contribute to airway narrowing and asthma, by reducing the extent to which bronchial muscle is stretched [ 4]. However, in the Nurses' Health Study the association between BMI and asthma was independent of physical activity [ 32]. The direction of the association is clearly difficult to determine from cross-sectional studies. Could asthma lead to obesity? Whilst a minority of individuals with asthma might avoid vigorous physical activity and thus put on weight, this would seem, at best, an incomplete explanation for the association. The longitudinal data from the Nurses' Health Study suggest that fatness precedes the onset of asthma in adults. Secondly, is the association strong and is there evidence of a ‘dose–response’? The two studies from Britain and the USA found substantial differences in the prevalence of asthma, when comparing women in the top part of the BMI distribution with those in the bottom part (odds ratio and relative risk of 2.0 and 3.0, respectively). Furthermore, the effect was graded across the whole distribution of BMI [ 31, 32], consistent with a causal relation. Thirdly, how consistent are the findings? The latest findings from Taiwan add to a substantial body of cross-sectional data linking fatness to asthma and wheeze. In keeping with the observation of a relation in girls but not in boys, the recent British study of young adults found that a strong association was present in women but not in men [ 31]. The association between BMI and atopy is a novel finding and, along with the findings for BHR, needs to be replicated in other population-based studies. The association between BMI and rhinitis in Taiwanese girls is surprising as previous studies of children and adults have found no relation between BMI and hay fever [ 15, 27, 31]. Fourthly, are there plausible mechanisms by which fatness might influence the expression of asthma? The gender difference in the findings from Taiwan and Britain is intriguing and suggests that sex hormones might play a part. In older women obesity is associated with higher levels of bio-available oestrogen [ 34] and there is some evidence that oestrogens may be a risk factor for asthma [ 35]. However, we need to identify other mechanisms to explain why fatness is also associated with asthma in young children and why fatness might be related independently to atopy. Huang et al. suggest that the lack of an association in boys in their study may simply be because BMI is not an equivalent measure of fatness in boys and girls. It would be of interest to clarify whether a gender difference in the association is also present in younger children. The nature of the association between fatness and asthma has yet to be clarified and at present we cannot say whether obesity per se has contributed to the rise in asthma. Whilst further observational studies, particularly longitudinal, would be of interest, the definitive test of whether fatness causes asthma must come from controlled intervention studies. A first step, in view of recent findings in children [ 18], might be a trial in asthmatic individuals to examine the impact of weight reduction on severity of disease. It remains to be seen whether asthma will be added to the list of chronic diseases linked to obesity [ 36], but for the moment we need to keep an open mind.