The Obese Asthma Phenotype in Children

Read Also

Obese children with asthma pose a hefty pediatric management challenge.  Several studies have evaluated asthma characteristics among lean and obese children.  Several reports suggest that asthma symptoms are more severe among obese children [38, 79-83] while others have found no difference in lung function or asthma severity [84-87].  Data suggest that obese asthmatics are at least as hard to control as their lean counterparts, and in some reports are less responsive to conventional therapies [88-90] [81, 82] [89, 91-93].  Much of the data describing obese asthma comes from adults.  Overall, obese adult asthmatics generally have similar lung function (or modest reductions in lung volumes) and airway responsiveness compared to lean asthmatics.  Obese adult asthmatics generally achieve reduced asthma symptom control and are less apt to have severe atopy and eosinophil-driven inflammation.  There is evidence that leukotrienes may play a more prominent role in the obese asthma phenotype [94].  Leukotriene production is up-regulated in patients with obesity [95] and is important in asthma pathogenesis [31, 32].  We previously determined the allele frequencies of the addition/deletion promoter polymorphism in the ALOX5 gene among a population of asthmatics undergoing a clinical trial [96, 97].  The ALOX5 gene encodes for 5-lipoxygenase which catalyzed the oxidation of membrane arachidonic acids to create LTA₄.  Recently we have analyzed the allele frequencies of this ALOX5 polymorphism among lean and obese participants of this study and a second population of obese and non-obese, otherwise healthy (non-asthmatic) volunteers (Table).

Among the non-asthmatics, 57% of obese individuals carried the variant allele compared to 40% for non-obese individuals.  The relative risk of obesity in individuals carrying the variant allele is 2.04 compared to carriers of the wild type (p = 0.0165). It is not clear if or how this promoter polymorphism contributes to obesity.  Nevertheless, it is rationale therefore to hypothesize that obese, non-asthmatic persons may be at greater risk for developing asthma due in part to the mutant ALOX5 variant and to greater upregulation of the leukotriene pathway compared to the those with the wildtype genotype[96, 98].  Furthermore, due to the higher prevalence of the ALOX5 variant in obese asthmatics, leukotriene levels may be elevated in a larger fraction of obese patients, thus making them prime candidates to benefit from therapies acting on the leukotriene pathway.