New R01 Study to Probe Connections Between Obesity and Asthma
May 28, 2020
The incidence of both obesity and asthma has been rising steadily in the United States. Centers for Disease Control and Prevention (CDC) data show that obesity rates in children and adolescents have increased three-fold since the 1970s.1 Rates of asthma also have been on the increase. National prevalence data from the CDC as of 2018 show that more than 5.5 million children and adolescents under the age of 18 in the United States have asthma.2
Evidence exists for an association between both diseases, such that people with obesity are at higher risk of asthma. Furthermore, individuals with asthma and obesity tend to have more severe asthma, worse symptom control, and a reduced response to asthma medications. However, the exact molecular and genetic mechanisms by which obesity may influence asthma in childhood are complex and not entirely known.
Erick Forno, MD, MPH, ATSF, assistant professor of pediatrics at the University of Pittsburgh and the Division of Pediatric Pulmonary Medicine at UPMC Children’s Hospital of Pittsburgh, obtained new R01 funding in March from the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) for studies3 that will probe the mechanisms by which obesity affects asthma in children and adolescents.
The central hypothesis of Dr. Forno’s studies is that obesity affects childhood asthma through epigenetic regulation and transcriptomic activity within adipose tissue. Epigenetic regulation is one of the ways the body regulates which genes are turned on or off; transcriptomic activity measures how much of each gene is being produced.
Dr. Forno’s studies will recruit cohorts of children and adolescents with asthma, obesity, or both, as well as control populations, in whom they will perform extensive phenotyping and obtain subcutaneous and intra-abdominal adipose tissue for study. The investigation will assess body mass index (BMI) in the study cohorts, along with other indices of adiposity and body composition measured by anthropometry and impedance analysis. Dr. Forno will examine the risk of asthma in children and adolescents with and without obesity; among children and adolescents with asthma, he will evaluate severity outcomes, including exacerbations, symptoms, and lung function. Dr. Forno will then study the top identified targets in the laboratory using normal and asthmatic bronchial epithelial and airway smooth muscle cells.
Dr. Forno previously received a K08 award from the NHLBI to study obesity and asthma in children4, and the current award is partly built on findings from that research.
Clinically Significant Research
“Our new studies are innovative in that they will focus on the ‘source’ tissue of children with asthma who are obese, rather than using blood biomarkers or mediators, and by validating the effect of the top results on the ‘target’ tissues,” says Dr. Forno. “Revealing the pathways in adipose tissue associated with asthma in the context of obesity will have critical implications for understanding this phenotype. It will allow us to identify ways to improve the management of these patients and may help identify therapeutic targets.”
References
1. https://www.cdc.gov/obesity/data/childhood.html
2. https://www.cdc.gov/asthma/most_recent_data.htm
3. Obesity and Childhood Asthma: The Role of Adipose Tissue. 1R01HL149693-01. Principal investigator: Erick Forno, MD, MPH, ATSF.
4. Obesity and Asthma Subphenotypes and Underlying Pathways. 5K08HL125666-04.
Further Reading
A selection of previously published research by Dr. Forno and colleagues on childhood asthma and obesity includes the following papers. For a complete list of Dr. Forno's publications, click here.
Gong Z, Zhang X, Su K, Jiang R, Sun Z, Chen W, Forno E, Goetzman ES, Wang J, Dong HH, Dutta P, Muzumdar R. Deficiency in AIM2 Induces Inflammation and Adipogenesis in White Adipose Tissue Leading to Obesity and Insulin Resistance. Diabetologia. 2019 Dec; 62(12): 2325-2339. Epub 2019 Sep 11.
Forno E, Zhang P, Nouraie M, Courcoulas A, Mitchell JE, Wolfe BM, Strain G, Khandelwal S, Holguin F. The Impact of Bariatric Surgery on Asthma Control Differs Among Obese Individuals With Reported Prior or Current Asthma, With or Without Metabolic Syndrome. PLoS One. 2019 Apr 9; 14(4): e0214730.
Okoniewski W, Lu KD, Forno E. Weight Loss for Children and Adults with Obesity and Asthma. A Systematic Review of Randomized Controlled Trials. Ann Am Thorac Soc. 2019 May; 16(5): 613-625.
Peters U, Dixon AE, Forno E. Obesity and Asthma. J Allergy Clin Immunol. 2018 Apr; 141(4): 1169-1179.
Forno E, Han YY, Libman IM, Muzumdar RH, Celedón JC. Adiposity and Asthma in a Nationwide Study of Children and Adults in the United States. Ann Am Thorac Soc. 2018 Mar; 15(3): 322-330.
Forno E, Han YY, Mullen J, Celedón JC. Overweight, Obesity, and Lung Function in Children and Adults-A Meta-analysis. J Allergy Clin Immunol Pract. 2018 Mar-Apr; 6(2): 570-581.
Forno E, Celedón JC. The Effect of Obesity, Weight Gain, and Weight Loss on Asthma Inception and Control. Curr Opin Allergy Clin Immunol. 2017 Apr; 17(2): 123-130.
Forno E, Weiner DJ, Mullen J, Sawicki G, Kurland G, Han YY, Cloutier MM, Canino G, Weiss ST, Litonjua AA, Celedón JC. Obesity and Airway Dysanapsis in Children With and Without Asthma. Am J Respir Crit Care Med. 2017 Feb 1; 195(3): 314-323.
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