Reviews and feature article
Obesity and asthma

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Information for Category 1 CME Credit

Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.

Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.

Date of Original Release: April 2018. Credit may be obtained for these courses until March 31, 2019.

Copyright Statement: Copyright © 2018-2019. All rights reserved.

Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.

Target Audience: Physicians and researchers within the field of allergic disease.

Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

List of Design Committee Members: Ubong Peters, PhD, Anne E. Dixon, MA, BM, BCh, and Erick Forno, MD, MPH (authors); Andrea Apter, MD, MA, MSc (editor)

Disclosure of Significant Relationships with Relevant Commercial

Companies/Organizations: A. E. Dixon has received grants from the National Institutes of Health, the American Lung Association, and Pfizer and has received personal fees from Vitaeris. The rest of the authors declare that they have no relevant conflicts of interest. A. Apter (editor) declares that she has no relevant conflicts of interest.

Activity Objectives:

  • 1.

    To understand the role that obesity plays as a risk factor for and disease modifier of asthma.

  • 2.

    To identify the mechanisms involved in asthma pathogenesis.

  • 3.

    To understand the evidence supporting lifestyle changes in influencing disease progression.

  • 4.

    To identify the clinical characteristics of obese asthma in children and adults.

Recognition of Commercial Support: This CME activity has not received external commercial support.

List of CME Exam Authors: Gagandeep Cheema, MD, Erica Ridley, MD, Eliane Abou-Jaoude, MD, and Christian Nageotte, MD.

Disclosure of Significant Relationships with Relevant Commercial

Companies/Organizations: The exam authors disclosed no relevant financial relationships.

Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.

Section snippets

Epidemiology of obesity and childhood asthma

Asthma affects approximately 6.5 million children (approximately 9% prevalence) in the United States.6 Likewise, 17% of children in this country are obese, and another 15% are overweight.7 Obesity is now recognized as a major risk factor for asthma: several longitudinal epidemiologic studies show that obesity or increased adiposity often precedes incident asthma.8, 9, 10, 11, 12, 13, 14, 15, 16 Many studies have reported differing obesity-asthma associations by sex,10, 17, 18, 19, 20 although

Epidemiology of obesity and asthma in adults

A meta-analysis of several prospective studies involving more than 300,000 adults found a dose-response relationship between obesity and asthma: the odds ratio of incident asthma was 1.5 in the overweight and 1.9 in the obese groups compared with the lean group; in effect, 250,000 new asthma cases per year in the United States are related to obesity.29 This relationship has radically changed the demographics of asthma in the United States: the prevalence of asthma in lean adults is 7.1%, and

Clinical characteristics of obese asthma in children

On occasion, asthma can predispose to obesity,31 obesity can confound its diagnosis,32, 33 or both can simply co-occur. However, the majority of observational and experimental evidence points to an “obese asthma” phenotype in which obesity modifies asthma.34, 35

Obese children tend to have increased asthma severity,36, 37, 38 poorer disease control,39 and lower quality of life.40 Many obese children with asthma tend to have TH1-skewed responses, particularly in response to inflammatory stimuli,

Clinical characteristics of obese asthma in adults

Much like children, obese adults tend to have more severe asthma than lean adults, with a 4- to 6-fold higher risk of being hospitalized compared with lean adults with asthma.47 Nearly 60% of adults with severe asthma in the United States are obese.48 Obese patients also have worse asthma control and lower quality of life.49 Obese asthmatic patients do not respond as well to standard controller medications, such as ICSs and ICS/long-acting β-agonist combination.50 The mechanisms behind the

Obesity and lung function in pediatric patients

Childhood obesity has a significant effect on lung function. Although our initial understanding of this phenomenon derived from studies in adults (described in the following section), as early as 1997, Lazarus et al57 reported that height-adjusted FEV1 and forced vital capacity (FVC) were greater in children with higher weight. Tantisira et al58 described that BMI was associated with higher FEV1 and FVC but a lower FEV1/FVC ratio among participants in CAMP.58 In a recent meta-analysis including

Lung function and AHR in obese adults

Obesity causes significant changes to normal lung physiology in adults (Fig 2). Excessive accumulation of fat in the thoracic and abdominal cavities leads to lung compression and an attendant reduction in lung volume.69 The most notable changes include a reduction in functional residual capacity and ERV.70, 71, 72 Radial traction of lung parenchymal attachments around the airways is attenuated at low lung volumes,73 which might contribute to airway collapse. Indeed, we have shown that obesity

The role of diet

Specific micronutrients might be involved in the association between obesity and asthma. Obesity is associated with low circulating vitamin D levels.79 Vitamin D deficiency might be a risk factor for the development of both obesity and asthma: prenatal vitamin D insufficiency has been associated with obesity in the offspring,80 and prenatal vitamin D supplementation led to a small decrease in the risk of wheezing illness at age 3 years (although this did not reach formal statistical

The microbiome and pathophysiology of obese asthma

Dietary changes lead to alterations in the gut microbiome, and changes characteristic of a Western dietary pattern, which promotes obesity, might also affect the development of allergic airway disease. Bacterial colonization of the gut plays a key role in fermentation of dietary fiber and generation of short-chain fatty acids (SCFAs). Obesogenic diets are typically high in fat and low in soluble fiber; low fiber is associated with changes in the gut microbiome and circulating SCFA levels.97

Inflammatory and metabolic changes in obese asthmatic patients

Many studies have reported that obesity-related asthma is more often nonatopic, yet some studies have reported that obesity in itself is associated with atopy.107, 108 In adolescents participating in the National Health and Nutrition Examination Survey, we found that obesity was associated with asthma only among participants with normal or low exhaled nitric oxide (NO; fraction of exhaled NO) levels; however, among those who already had asthma and high fraction of exhaled NO levels, obesity was

Genetics, epigenetics, and genomics

Both asthma and obesity have a considerable hereditary component, and thus investigators have studied whether there are genetic variants that might represent a link; to date, these studies have been somewhat inauspicious. Candidate gene studies have reported a few genes associated with asthma and BMI, such as PRKCA, LEP, and ADRB3.134, 135, 136 The largest pediatric genome-wide association study to date, which included more than 23,000 children and adults, reported on the gene DENND1B, although

Lifestyle weight-loss interventions

Studies published on the effects of various weight-loss interventions on asthma control find significant improvements in both asthma control and spirometric lung function with sufficient weight loss (Table I).53, 144, 145, 146, 150, 151, 152, 153, 155, 156 Interventions vary from liquid diet replacement to a more graduated dietary education approach. In adults it appears that weight loss of at least 5% is required to produce a significant improvement in asthma control.152 Typically, this is

Bariatric surgery

The effects of bariatric (weight-loss) surgery have been reported by a number of investigators.158, 159, 160 It is the most effective intervention for producing sustained and significant weight loss, and all studies have reported highly significant improvements in asthma control, airway reactivity, and lung function (Fig 2). Bariatric surgery also has significant effects on asthma exacerbations. Hasegawa et al161 studied 2261 patients with asthma using a population emergency department and

Conclusions

Obesity is an important risk factor for asthma and asthma morbidity, both in children and adults. Although there are many common pathophysiologic and clinical commonalities, certain characteristics differ between both age groups. This is a reflection of an obese asthma syndrome that is complex and multifactorial. Potential underlying mechanisms include a shared genetic component, dietary and nutritional factors, alterations in the gut microbiome, systemic inflammation, metabolic abnormalities,

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    E.F.'s contribution was supported in part by grants HL125666 and HL119952 from the US National Institutes of Health (NIH), a grant from Children's Hospital of Pittsburgh of UPMC, and an award from the Klosterfrau Foundation. U.P. and A.D. were supported by NIH grants HL133920 and HL130847.

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