Links Between Obesity and Childhood Asthma

Both asthma and obesity have been cited as major health problems among children worldwide, and findings show that their prevalence is increasing. In the United States, the Centers for Disease Control and Prevention reported that the prevalence of obesity among youth aged 2 to 19 years was 18.5% during 2015 and 2016, and the prevalence of asthma among youth younger than 18 years was 8.4% in 2017.^1,2

Obesity has been identified as a major risk factor for childhood asthma, and has been linked to lower treatment response and quality of life in this patient group. “Even though overweight/obesity and asthma may simply co-exist in some children, growing evidence underlines the existence of an ‘obese asthma’ phenotype in which high body weight affects and modifies asthma characteristics,” according to a review published in November 2018 in Nutrients.³ This phenotype has been characterized by “additional symptoms, worse control, more frequent and severe acute episodes, reduced response to inhaled corticosteroids, and lower quality of life than other phenotypes.”³

A wide range of study results support associations between obesity and asthma, including those highlighted here:

• Prospective studies have shown that asthma risk was increased by 2-fold in children classified as obese vs nonobese.⁴
• In a cohort study of 2450 fourth-grade children with new-onset asthma, long-term adiposity was linked to reduced pulmonary function, and rapid adiposity was associated with airway inflammation and atopic diseases.⁵
• In studies that examined hospital database records, obese children with asthma demonstrated worse symptoms and quality of life, higher gastroesophageal reflux scores, more frequent use of rescue therapies, and a higher risk of visiting the emergency department (ED) compared with nonobese children.³
• Children and adolescents with obesity had 24% greater odds of being unresponsive to bronchodilator therapy compared with lean patients in a 2015 study.⁶

Some findings also suggest that children with asthma have an elevated risk of developing obesity.

In research published in 2017, patients who used rescue drugs had a lower risk of developing obesity than those who did not use these therapies.⁵

“A bidirectional association between asthma and [being] overweight is possible, since many patients with asthma avoid physical activity, increase sedentary time, and swallow oral corticosteroid medications, which are three conditions that facilitate weight gain,” wrote the review authors.³ “Obesity and asthma share genetic, developmental, lung mechanical, immunological, and behavioural factors that can clarify their association,” they concluded. Additional research is needed to elucidate this association and the mechanisms involved.

Pulmonology Advisor interviewed Ronald Ferdman, MD, attending physician at Children’s Hospital Los Angeles, California, and associate professor of clinical pediatrics in the Division of Clinical Immunology and Allergy at Keck School of Medicine of the University of Southern California, for further discussion regarding the connection between obesity and childhood asthma.

Pulmonology Advisor: What is known thus far about links between obesity and childhood asthma, including potential underlying mechanisms?

Dr Ferdman: I believe it is well-recognized that there is a link between asthma and obesity, not only in children but also in adults. The bottom line is that obese children have more asthma, and their asthma tends to be more severe and less responsive to treatment compared with same-age children who are not obese. Obese children with asthma have worse scores on quality-of-life inventories. They are more likely to end up in the ED for asthma exacerbations, and once in the ED, they are more likely to need hospital admission (vs being able to be sent home) than nonobese children. Their asthma seems to be less steroid responsive.

Different phenotypes or endotypes of asthma have been described in the past; for example, early-onset asthma, late-onset asthma, eosinophilic or allergic asthma, neutrophilic asthma, and so on. Most people consider obesity-related asthma as a separate phenotype or endotype. The reason for this is that, although the exact mechanisms behind obesity-associated asthma are unknown, it does seem to have both some distinct mechanisms and differential response to treatment.

There are at least 2 major broad mechanisms contributing to obesity asthma. The first is more mechanical: the extra adipose tissue can compress lung volume, restrict chest wall movement, and make it more difficult to take deep breaths. The second is immunologic: obesity is well recognized to be pro-inflammatory, and inflammation is associated with many diseases, the most familiar being cardiovascular disease and diabetes. The inflammatory effects of asthma involve both the adaptive and innate immune systems.

In children more than in adults, obesity seems to be a trigger and Th2-type inflammatory response; that is, an allergic or immunoglobulin E-mediated response. But components of the innate immune system are also altered in obesity, including innate lymphoid cells (ILCs), and specifically ILC3, but also macrophages and neutrophils. The involvement of the innate immune system may be one reason why obesity-related asthma does not respond as well to conventional asthma therapy.

As with, it seems, just about every other disease in humans, the microbiome may be involved in obesity-associated asthma. Again, it is well-recognized that obese patients have a different microbiome than nonobese patients, and the same mechanisms through which the microbiome contributes to obesity may also increase asthma. Obese patients tend to eat more calories, and their diets also are oftentimes “less nutritious”; for example, including more sugars, carbohydrates, and saturated fats.

So, it seems it is not only the quantity of food eaten, but also the quality that contributes to the increased risk for asthma. [Editor’s note: In a recent study,⁷ higher dietary intake of omega 3 fatty acids was associated with a reduced effect of indoor air pollution on symptoms of pediatric asthma, whereas higher intake of omega 6 fatty acids had the opposite effect (P <.01) and was also associated with worse asthma severity (P =.02), and lower FEV1/FVC ratio (P =.01).]

Also, obese patients are often less active. Exercise has anti-inflammatory effects, so lack of exercise can also be viewed as pro-inflammatory.

Pulmonology Advisor: What are the main treatment implications for clinicians? For example, are physicians screening for asthma in children who present as obese? How often are these patients referred out to pulmonologists?

Dr Ferdman: I think it is important to know that obese patients will respond less well to asthma treatment. They are less steroid-responsive, and clinicians need to be cautious prescribing systemic “steroid bursts” as is commonly done in most patients with asthma, as not only are they less likely to be effective but they will also increase hunger and potentially worsen weight gain. It seems logical that weight loss will improve asthma in obese patients, and although there is some evidence for this, and I personally believe this to be true, there unfortunately are not a lot of studies in children to support this.

I think that one of the reasons for this is that it is simply very hard to get obese children to lose weight at all, not to mention to keep the weight off. In adults, bariatric surgery has been shown to result in long-term asthma improvement, but bariatric surgery is rare in children. Although caloric restriction is probably the most important step, quality of diet, as mentioned earlier, is also important. Exercise, both for weight loss and for its anti-inflammatory effects, is also important.

I don’t believe that physicians are routinely screening obese children for asthma, and I don’t think one necessarily needs to screen all obese children for asthma. In contrast, I do believe the incidence of asthma in obese children is probably underrecognized. So, while I don’t advocate screening all children, clinicians should have a low threshold to suspect asthma in obese children with any chronic or recurrent respiratory complaints. For example, I think it is probably not uncommon for clinicians, and parents for that matter, to “blame” an obese child’s inability to exercise on “weight,” when some of these children have unrecognized asthma.

I am an allergist and not a pulmonologist, so I don’t want to speak for them. However, my guess is that in general, clinicians are not referring children to asthma specialists based solely on the obesity. They probably are referring for difficult to control asthma, just as they would for difficult to control asthma in nonobese patients. There probably are children referred to pulmonologists primarily because of their obesity, but I’d venture that it’s based more on concern for sleep-related problems such as [obstructive sleep apnea] or hypoventilation than for asthma.

Pulmonology Advisor: What do the data show regarding long-term outcomes in children who remain obese into adulthood?

Dr Ferdman: I am unaware of any long-term studies looking at outcomes in children who remain obese into adulthood, and this would be an excellent research avenue. There is at least one study I am aware of that looked at obesity and aging in younger children. It showed that children who were obese before 6 to 7 years of age, but who lost weight by 6 to 7 years of age, did not have increased airway hyperreactivity by the time they were 8+ years old.⁸ However, those children who were still obese at 6 to 7 years old did have airway hyperreactivity when older.

So, there is at least some evidence that the longer one is obese, there is potential for long-term effects. My opinion is that if we [consider] the effect of obesity on the risk for cardiovascular disease and diabetes, that the risk for asthma will continue as long as the person is obese, even into adulthood. Basically, this is the same question as, “Does asthma in obese patients improve with weight loss?” My impression is that children with asthma who remain obese likely have more asthma as adults, and those who lose weight have less asthma, but this has not been proven.

Pulmonology Advisor: What further research is needed in this area?

Dr Ferdman: Additional studies are needed regarding the mechanisms of obesity-related asthma. Also, what treatment works the best for these patients, and is there any testing that we as clinicians can do to help guide treatment? What are the effects of weight loss and type of diet? Is there some meaningful treatment for the microbiome that might work? So far, treatments to modify the microbiome have had poor therapeutic effect in many diseases, including allergic diseases.

References

1. Centers for Disease Control and Prevention. Childhood obesity facts. https://www.cdc.gov/obesity/data/childhood.html. Updated August 13, 2018. Accessed April 9, 2019.
2. Centers for Disease Control and Prevention. Asthma. https://www.cdc.gov/nchs/fastats/asthma.htm Updated January 19, 2017. Accessed April 9, 2019.
3. Di Genova L, Penta L, Biscarini A, Di Cara G, Esposito S. Children with obesity and asthma: which are the best options for their management? Nutrients. 2018;10(11):1634.
4. Chen YC, Dong GH, Lin KC, Lee YL. Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: a systematic review and meta-analysis. Obes Rev. 2012;14:222-231.
5. Chen Z, Salam MT, Alderete TL, et al. Effects of childhood asthma on the development of obesity among school-aged children. Am J Respir Crit Care Med. 2017;195(9):1181-1188.
6. McGarry ME, Castellanos E, Thakur N, et al. Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest. 2015;147(6):1591-1598.
7. Brigham EP, Woo H, McCormack M, et al. Omega-3 and omega-6 intake modifies asthma severity and response to indoor air pollution in children [published online March 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201808-1474OC
8. Garcia-Marcos L, Arnedo Pena A, Busquets-Monge R, et al. How the presence of rhinoconjunctivitis and the severity of asthma modify the relationship between obesity and asthma in children 6-7 years old. Clin Exp Allergy. 2008;38(7):1174-1178.