Childhood obesity and asthma –to BMI or not to BMI?

Over the past several decades there has been a rise in the prevalence of both childhood obesity and childhood asthma, and we have seen a corresponding increase in the epidemiological and scientific evidence that obesity can increase childhood asthma risk and morbidity^1,2. Observational and experimental studies have outlined several potential causal mechanisms,^3,4 and while our understanding of the “obese asthma” phenotype is far from complete, it has become evident that it is likely complex and multifactorial –much like both of the diseases involved.

One of the main difficulties in studying obese asthma emerges from our current definition of obesity based on the body mass index (BMI). The formula for BMI was first proposed 180 years ago by Belgian astronomer, statistician and sociologist Adolphe Quételet in an attempt to describe the l’homme moyen –the average man⁵. After considering weight/height³ for infants, weight/height² for children, and weight²/height⁵ for adolescents and adults, he eventually settled for a simplified weight/height². Several weight and height iterations were subsequently proposed, until Ancel Keys coined the term “body mass index” in a 1972 study comparing several indices to a golden standard –the sum of tricipital and subscapular skinfolds– in 7,424 healthy adult men⁶. Thereafter BMI was quickly adopted as a measure of obesity and in 1985 the National Institutes of Health (NIH) published a consensus statement recommending the use of BMI in the evaluation of obesity⁷.

Despite its simplicity (or, rather, precisely because of it), BMI has several limitations. Quételet aimed to describe the average man, not dictate the definition of obesity. The study by Keys et al. did not include children or women. BMI is not intended to differentiate between lean and fat mass. It provides no information on the distribution of adipose tissue depots, which may have crucial implications for different diseases. Ironically, the 1985 NIH statement already reported that “recent studies suggest that the distribution of fat deposits may be a better predictor of mortality” than BMI.

In this issue of the Journal, den Dekker et al. address precisely some of these issues by evaluating whether BMI or other measures of adipose tissue distribution are associated with asthma and lung function⁸. In a cross-sectional analysis of a population-based cohort of 6,178 children, the authors measured BMI, body fat mass and its android/gynoid ratio by dual-energy X-ray absorptiometry (deXa), and subcutaneous and pre-peritoneal fat mass by ultrasound. They found BMI to be associated with higher risk of reported wheezing and with higher airway resistance measured by Rint. The body fat mass index was also associated with Rint, but neither general indicator was associated with FeNO, a marker of eosinophilic airway inflammation. In contrast, more localized measures of fat distribution were associated with FeNO: the android/gynoid fat mass ratio was associated with lower FeNO, whereas the amount of pre-peritoneal fat was associated with higher FeNO. Subcutaneous fat mass did not show any significant associations.

These findings carry two important implications: First, certain adipose tissue distribution patterns may be linked to specific pathways underlying the effect of obesity on asthma. In this case, pre-peritoneal fat may be linked to allergic, eosinophilic-driven airway inflammation. Pre-peritoneal fat represents the circumferential margins of the anterior peritoneum (i.e. the intra-abdominal fat that directly underlies the abdominal wall) and is seen as lateral “flank stripes” on abdominal x-ray. The android/gynoid index, on the contrary, encompasses several abdominal and subcutaneous fat depots. Pre-peritoneal fat has been associated with cardiovascular disease in adolescents⁹, fatty liver¹⁰, serum insulin levels¹¹, and other changes associated with the metabolic syndrome¹². The finding in the setting of asthma is novel and interesting, and certainly deserves further exploration.

Second, and more generally, the study by den Dekker and colleagues highlights the importance of not limiting our study of obese asthma to the incomplete picture portrayed by BMI. In a recent case-control study of asthma in Puerto Rican children, waist circumference and percent body fat showed associations with exercise-induced asthma symptoms, FEV₁/FVC, total IgE, and allergic rhinitis that BMI did not¹³. Similarly, Chen et al. found central obesity to most accurately predict asthma in a survey of Taiwanese schoolchildren¹⁴. Moreover, it may be the metabolic complications of obesity, rather than obesity itself, that affect lung function and asthma risk and morbidity in children^15–17.

The study is not without limitations, including attrition bias (mother-child dyads who were lost to follow-up differed from those who remained in the cohort) and the lack of other, more widely utilized measures of lung function such as FEV₁ or FEV₁/FVC. The proportion of obese children was relatively low at 4.5% (certainly low compared to the prevalence of childhood obesity in the U.S.), which may have resulted in limited statistical power to detect small effects. More importantly, the obesity measures were obtained at the same time as the outcomes, and therefore this cross-sectional analysis cannot determine temporality or causality. Future research should address these limitations by performing prospective studies with more detailed characterization of adipose tissue distribution and more detailed account of asthma-related outcomes.

To be clear, not all children with obesity and asthma necessarily have “obese asthma”. In some cases, both diseases may simply coexist without being causally related. In other instances, obese children and adults may exhibit symptoms that resemble asthma or may lead to misdiagnosis^18,19. Some children with severe asthma may be at higher risk of obesity. But studies like the one in this issue of JACI recognize the complexity of the phenotype, and take a step in the right direction to better understand it. It is not possible to comprehend the effect of obesity on childhood asthma by using BMI alone, just like we cannot understand everything about asthma solely by measuring FEV₁.