Obesity has been inconsistently shown to increase asthma morbidity, which may be partly explained by the fact that weight gain does not appear to affect all asthmatic subjects alike. Evidence to support this assertion comes from recent cluster studies showing that having a larger body mass index (BMI) is part of an asthma phenotype characterized by adult onset asthma, female preponderance and less atopy 1, 2. Also, a large epidemiological study showed stronger associations between asthma and obesity among non-allergic women 3. The fact that increasing BMI has been unexpectedly associated with reduced biomarkers of Th2-related inflammation, such as exhaled NO and sputum eosinophils also supports a relationship between obesity with predominantly non-Th2-mediated inflammation 4, 5. Although it is entirely expected that weight gain can worsen respiratory symptoms in most asthmatics, it is perhaps in this specific cluster that obesity is a major risk factor for increased asthma severity. Further, as shown by Dixon et al. the effects of weight loss on asthma differ according to the underlying clinical phenotype 6. In their study, obese asthmatics were prospectively evaluated at baseline and 1 year after bariatric surgery. Although all asthmatics experienced significant improvements in quality of life and asthma control, there was a significant interaction between weight loss and bronchial hyperresponsiveness, with the greatest improvements seen among those with normal IgE levels. As current evidence points towards the existence of predominantly non-Th2 obesity–asthma phenotype, the article by Fitzpatrick et al. 7 published on this issue of the journal, suggests that obesity is associated with increased asthma severity and allergic inflammation. This is a retrospective cross-sectional study comprised of a population of atopic, mostly African American asthmatic adults, of which 50% were obese. Compared with their leaner counterparts, obese asthmatics were more likely to be classified as having severe asthma and those with a BMI > 35 were more likely to use more inhaled and oral corticosteroids. Also, obesity was associated with increased serum IgE levels and increased blood neutrophils. Compared with leaner asthmatics, overweight, but not obese subjects, had higher peripheral eosinophil counts. How to then interpret these findings, which by showing an association between obesity and increased allergic inflammation, depart from what others have shown? Several characteristics related to the uniqueness of the study population and to the study design, may explain why Fitzpatrick et al. found these contrasting results. First, the presence of atopy determined by a history of skin allergy testing was an inclusion criterion that biased the study population towards greater indices of allergic inflammation. Second, among African Americans, elevated IgE levels are strongly associated with increased asthma severity 8, which via reduced physical activity and greater steroid use could lead to increase risk of obesity. Clearly, given the cross-sectional design of the study it is impossible to determine whether asthma severity preceded obesity. However, data from the Severe Asthma Research Program supports this assertion by showing that early onset asthmatics, which are also more likely to have atopy and greater allergic inflammation, increase their BMI at a steeper rate when compared with late-onset, less atopic asthmatics 9. There are important research and clinical implications that can be derived from this study. The generalizability of these results would imply that among atopic asthmatics of predominantly African Americans descent, obesity increases the odds for allergic inflammation; however, given our current understanding of asthma phenotypes, it is possible that in this case obesity is the result rather than the cause of increased asthma severity and elevated IgE levels. Although the authors argue that that obesity could lead to elevated IgE levels through an obesity-mediated pro-inflammatory state, an interaction between adiposity with asthma on biomarkers of inflammation has not been shown to occur in humans. Perhaps our inability to demonstrate this interaction results from heterogeneity of the susceptibility that asthmatics have to being obese. Just like not every asthmatic is sensitive to pollen, or cat dander; why should we expect obesity to be any different? In our quest to identify the mechanisms by which obesity affects asthma, perhaps we should, with equal enthusiasm, try to identify the cluster of asthmatics in whom disease process is more adversely affected by this condition (beyond increased dyspnoea); whether the adult onset asthmatic with less atopy constitute this phenotype, is yet to be proven. However, until we do this, it will be difficult to fully understand the underlying pathophysiological mechanisms and develop differential or personalized treatment approaches. Moreover, we will be unable to identify in cross-sectional studies, whether or not obesity is indeed a cause or an effect.
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Jan 1, 2013
Jarmila Čelakovská + 3
Open Access
