Addressing Asthma Comorbidities and Different Phenotypes

Speakers discussed asthma development and phenotypes associated with disease severity during a session at the 2018 AAAAI Annual Meeting.

Leonard B. Bacharier, MD, FAAAAI, of the Washington University School of Medicine in St. Louis, Missouri, said, “We’ve come to recognize that asthma—especially in early life—is a syndrome.”

He discussed the 2011 URECA study published by Wood et al in the Journal of Allergy and Clinical Immunology, in which researchers followed 560 children from allergic families in poor urban neighborhoods in Baltimore, Boston, New York, and St. Louis. Positive associations were detected between multiple wheeze and cotinine levels, maternal stress, and maternal depression, while cytokine responses to a variety of innate, adaptive, and mitogenic stimuli were inversely related to eczema. An update to the study, published by Gern et al, found that exposure to certain allergens (e.g., cockroach, mouse, and dust mite) was significantly associated with enhanced cytokine responses at 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. These types of studies “may help identify asthma endotypes and suggest new approaches to prevention of asthma,” Dr. Bacharier said. However, the problem is that “most cohort studies have focused on development of wheeze or atopy,” he said.

Jean Julien Bousquet, MD, PhD, of CHU-Montpellier in France, discussed the role of rhinitis in asthma severity. He noted that rhinitis is an independent risk factor for adult-onset asthma. According to a 2005 study published by Price et al in Clinical & Experimental Allergy, allergic rhinitis increased the risk of hospitalization for asthma by 50%. While severe rhinitis and severe asthma appear to be correlated, this trend does not hold true for rhinitis and chronic obstructive pulmonary disease, he said.

Dr. Bousquet concluded by discussing the Allergy Diary app, which allows users to keep a daily record of allergic rhinitis, asthma symptoms, and medication use. The app is available in 23 countries and in 16 languages and has 18,000 users. Click here to learn more.

Meredith C. McCormack, MD, of Johns Hopkins Medicine in Baltimore, Maryland, closed the session by talking about the role of obesity in asthma severity. Asthma prevalence has increased over the year, as has obesity, she said, prompting researchers to look at this. There is an increased risk of incident adult asthma when the condition of obesity is met; however, there is a sex difference: Women tend to have an increased risk of asthma that is exaggerated in the presence of asthma. While the correlation between obesity and asthma has been studied in adults, the trend in children is unknown.

She discussed two distinct obese asthma phenotypes:

• Early-onset atopic:
  • Classic Th2 mediated inflammatory disease
  • Cytokines made by leptin and fat tissue may contribute to chronic inflammation
• Later onset, non-atopic
  • Obese patients are at increased risk
  • Adipose-related cytokines and restrictive physiology
  • Breathing at low lung volumes may increase airway hyperresponsiveness

Studies of later onset, non-atopic obesity have shown that weight loss may improve asthma outcomes in children. Many factors are related to overweight/obesity and asthma, including diet, respiratory mechanics, physical activity, comorbidities (e.g., sleep apnea, gastroesophageal reflux disease, metabolic syndrome, and cardiovascular disease), glucocorticoid resistance, inflammation, oxidative stress, hormones, and adipokines.

She highlighted some studies that addressed some comorbidities and asthma outcomes. A 2016 study published by Forno et al in the American Journal of Respiratory and Critical Care Medicine assessed whether childhood obesity is associated with airway dysanapsis and whether dysanapsis is associated with asthma morbidity. Overweight/obesity was associated with dysanapsis in both cross-sectional (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and longitudinal (OR, 4.31; 95% CI, 2.99-6.22) analyses.

A meta-analysis of 32 studies found that children with asthma were more likely to develop snoring and obstructive sleep apnea, but treatment with adenotonsillectomy improved asthma outcomes. Another study found that obesity is a risk factor for reduced response to omalizumab in patients with severe asthma. Obesity was also associated with poor asthma control and elevated fractional exhaled nitric oxide while on omalizumab. A study assessed the impact of diet and wheezing: A Western diet (defined as high consumption of red meat, processed meat, refined grains, sweets, and desserts) had a positive statistically significant association with wheeze (OR, 1.77, 95% CI, 1.10-2.84) compared with the Prudent diet (defined as high in fruits, vegetables, legumes, fish, and poultry).

“We need to identify treatment approaches for obese patients with asthma…as it is a unique phenotype that is associated with more severe asthma,” said Dr. McCormack. More research on the impact of diet, exercise, and weight loss is needed, as well as a focus on treatment of comorbidities.

Presentation 1519: Insights into Asthma Development and Severity