Reviews and feature article
Obesity and asthma

https://doi.org/10.1016/j.jaci.2020.08.011Get rights and content

Obesity has been well recognized as an important comorbidity in patients with asthma, representing a unique phenotype and endotype. This association indicates a close relationship between metabolic and inflammatory dysregulation. However, the detailed organ-organ, cellular, and molecular interactions are not completely resolved. Because of that, the relationship between obesity and asthma remains unclear. In this article, clinical and epidemiological studies, as well as data from experimental animal work, are being summarized to provide a state of the art update on this important topic. Much more work is needed, particularly mechanistic, to fully understand the interaction between obesity and asthma and to develop novel preventive and therapeutic strategies.

Section snippets

Obesity and asthma: Adults

Data noted in the literature regarding obesity and asthma are inconsistent. It is generally accepted that obesity is a risk factor for adult asthma. Ten years ago a workshop report of the American Thoracic Society officially documented obesity as a risk factor for asthma in all demographic groups.1 Asthma in the obese may represent a unique phenotype of asthma, with a more severe disease outcome that does not respond as well to conventional therapy. Factors that could contribute to the

Experimental models

The development of allergic and other noncommunicable systemic diseases is a multifactorial process in which, besides genetic predisposition, the environment (allergen exposure, nutrients) and immunologic mechanisms play a decisive role. In particular, the highly complex interactions of different cell types of the immune system and tissues cannot be imitated in vitro. Therefore, mouse models offer the opportunity to study the complex interactions between the fatty tissue and the inflammatory

Detailed metabolic assessment: Immune-metabolic interventions

Association of asthma and obesity has been demonstrated in numerous epidemiological studies; however, the exact underlying mechanisms and detailed pathogenic link for this association are not well understood. A large number of factors are postulated including inflammation and immunometabolic dysregulation,50, 51, 52, 53, 54 microbial dysbiosis,55 mitochondrial dysfunction,56 free fatty acid receptors,57 glucagon-like peptide pathway,58 and innate lymphoid cells (Fig 1).28

It has been shown that

Is asthma a risk factor for obesity?

Several studies have shown the correlation between childhood obesity and the resulting increased risk for developing asthma.102 So far little is known about the reversed order of asthmatic children having a higher risk for obesity incidence. A longitudinal study in the United States of early-life history of asthma demonstrated a higher risk of becoming obese in later childhood and adolescence.19 A European study demonstrated that not only asthma but also childhood wheezing and allergic rhinitis

Conclusions

Recent clinical, epidemiological, and experimental data strengthen the cause-effect relationship between obesity and asthma. Obesity is the result of metabolic dysregulation on the level of sugar and lipid metabolites. The adipose tissue is functionally highly active, which is reflected by the presence of local and systemic subclinical inflammation. This inflammatory response seems to contribute to airway inflammation, lung function, and asthma exacerbation. However, many open questions remain,

References (104)

  • S.A. Shore et al.

    Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

    J Allergy Clin Immunol

    (2006)
  • L. Zhu et al.

    Adiponectin alleviates exacerbation of airway inflammation and oxidative stress in obesity-related asthma mice partly through AMPK signaling pathway

    Int Immunopharmacol

    (2019)
  • V.P. Singh et al.

    House dust mite allergen causes certain features of steroid resistant asthma in high fat fed obese mice

    Int Immunopharmacol

    (2018)
  • D.Y. Kim et al.

    Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model

    Eur J Pharmacol

    (2009)
  • P. Bi et al.

    Notch signaling as a novel regulator of metabolism

    Trends Endocrinol Metab

    (2015)
  • Z. Zeng et al.

    Inhibiting the Notch signaling pathway suppresses Th17-associated airway hyperresponsiveness in obese asthmatic mice

    Lab Invest

    (2019)
  • L.O.S. Leiria et al.

    Obesity and asthma: beyond T(H)2 inflammation

    Metab Clin Exp

    (2015)
  • K. Mizuta et al.

    Obesity-induced asthma: role of free fatty acid receptors

    Jpn Dent Sci Rev

    (2019)
  • D.-V. Nguyen et al.

    Obesity-related, metabolic asthma: a new role for glucagon-like peptide 1 agonists

    Lancet Respir Med

    (2017)
  • M.W. Lee et al.

    Activated type 2 innate lymphoid cells regulate beige fat biogenesis

    Cell

    (2015)
  • S. Carraro et al.

    Asymmetric dimethylarginine in exhaled breath condensate and serum of children with asthma

    Chest

    (2013)
  • H.M.A. Eid et al.

    Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine

    Metab Clin Exp

    (2004)
  • A. Bianco et al.

    The burden of obesity in asthma and COPD: role of adiponectin

    Pulm Pharmacol Ther

    (2017)
  • S.C. Jenkins et al.

    The effects of mild obesity on lung function

    Respir Med

    (1991)
  • L.C. Collins et al.

    The effect of body fat distribution on pulmonary function tests

    Chest

    (1995)
  • R.L. Jones et al.

    The effects of body mass index on lung volumes

    Chest

    (2006)
  • M.S. Biring et al.

    Pulmonary physiologic changes of morbid obesity

    Am J Med Sci

    (1999)
  • F. Zerah et al.

    Effects of obesity on respiratory resistance

    Chest

    (1993)
  • R. Lazarus et al.

    Effects of obesity and fat distribution on ventilatory function: the normative aging study

    Chest

    (1997)
  • S. Pakhale et al.

    Effects of weight loss on airway responsiveness in obese adults with asthma: does weight loss lead to reversibility of asthma?

    Chest

    (2015)
  • A.E. Dixon et al.

    An official American thoracic society workshop report: obesity and asthma

    Proc Am Thorac Soc

    (2010)
  • D.A. Beuther et al.

    Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies

    Am J Respir Crit Care Med

    (2007)
  • E.R. Sutherland et al.

    Cluster analysis of obesity and asthma phenotypes

    PLoS One

    (2012)
  • B.M. Brumpton et al.

    Metabolic syndrome and incidence of asthma in adults: the HUNT study

    Eur Respir J

    (2013)
  • N. Assad et al.

    Body mass index is a stronger predictor than the metabolic syndrome for future asthma in women. The longitudinal CARDIA study

    Am J Respir Crit Care Med

    (2013)
  • J.C. Cardet et al.

    Insulin resistance modifies the association between obesity and current asthma in adults

    Eur Respir J

    (2016)
  • F.-J. Gonzalez-Barcala et al.

    Obesity does not increase the risk of asthma readmissions

    J Clin Med

    (2020)
  • E. Melén et al.

    Analyses of shared genetic factors between asthma and obesity in children

    J Allergy Clin Immunol

    (2010)
  • E. Melén et al.

    Genome-wide association study of body mass index in 23 000 individuals with and without asthma

    Clin Exp Allergy

    (2013)
  • L. Wang et al.

    Genome-wide gene by environment interaction analysis identifies common SNPs at 17q21.2 that are associated with increased body mass index only among asthmatics

    PLoS One

    (2015)
  • R. Granell et al.

    Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study

    PLoS Med

    (2014)
  • T. Skaaby et al.

    Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

    Allergy

    (2018)
  • D.S. Freedman et al.

    BMI z-scores are a poor indicator of adiposity among 2- to 19-year-olds with very high BMIs, NHANES 1999-2000 to 2013-2014

    Obesity

    (2017)
  • Z. Chen et al.

    Effects of childhood asthma on the development of obesity among school-aged children

    Am J Respir Crit Care Med

    (2017)
  • E. Forno et al.

    Maternal obesity in pregnancy, gestational weight gain, and risk of childhood asthma

    Pediatrics

    (2014)
  • M. Kleinert et al.

    Animal models of obesity and diabetes mellitus

    Nat Rev Endocrinol

    (2018)
  • A.T. Nials et al.

    Mouse models of allergic asthma: acute and chronic allergen challenge

    Dis Model Mech

    (2008)
  • H.-T.T. Tan et al.

    Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice

    Allergy

    (2019)
  • N. Jovicic et al.

    Differential immunometabolic phenotype in Th1 and Th2 dominant mouse strains in response to high-fat feeding

    PLoS One

    (2015)
  • J. Dietze et al.

    Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma

    Allergy

    (2012)
  • Cited by (0)

    H.R. is supported by the German Lung Centre (DZL).

    Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

    Shared first authorship.

    Shared last authorship.

    View full text