Reviews and feature article
Obesity and asthma: Possible mechanisms

https://doi.org/10.1016/j.jaci.2008.03.004Get rights and content

Epidemiologic data indicate that obesity increases the prevalence and incidence of asthma and reduces asthma control. Obese mice exhibit innate airway hyperresponsiveness and augmented responses to certain asthma triggers, further supporting a relationship between obesity and asthma. Here I discuss several mechanisms that may explain this relationship. In obesity, lung volume and tidal volume are reduced, events that promote airway narrowing. Obesity also leads to a state of low-grade systemic inflammation that may act on the lung to exacerbate asthma. Obesity-related changes in adipose-derived hormones, including leptin and adiponectin, may participate in these events. Comorbidities of obesity, such as dyslipidemia, gastroesophageal reflux, sleep-disordered breathing, type 2 diabetes, or hypertension may provoke or worsen asthma. Finally, obesity and asthma may share a common etiology, such as common genetics, common in utero conditions, or common predisposing dietary factors. Novel therapeutic strategies for treatment of the obese patient with asthma may result from an increased understanding of the mechanisms underlying this relationship.

Section snippets

Mechanical factors

In the obese, the functional residual capacity (FRC) is reduced because of changes in the elastic properties of the chest wall.20 The retractive forces of the lung parenchyma on the airways are reduced at low lung volumes, and a lower FRC may unload the airway smooth muscle (ASM), so that it shortens more when activated either by normal parasympathetic tone, or by other bronchoconstricting agonists (Fig 2).12 Indeed, breathing at low lung volume has been shown to increase airway responsiveness.

Chronic systemic inflammation

It is now well established that obesity is a state of chronic low-grade systemic inflammation. Using microarray, several groups have established that the genes whose expression differs most in the adipose tissue of obese versus lean mice or human beings are inflammatory genes, including cytokines, chemokines, complement proteins, and other acute-phase moieties,41, 42 collectively termed adipokines. The current paradigm is that this inflammation spills over into the blood, leading to

Energy-regulating hormones

Obesity also results in changes in adipose tissue–derived energy-regulating hormones. I discuss possible roles for 2 of these hormones, leptin and adiponectin, in the relationship between obesity and asthma.

Comorbidities

As previously discussed,10, 11, 12 it is also possible that comorbidities of obesity, such as dyslipidemia, gastroesophageal reflux disease (GERD), sleep-disordered breathing (SDB), or type 2 diabetes, may provoke or worsen asthma.

Common etiologies

As proposed by others,8, 13 it is possible that obesity and asthma share a common etiology, and that increases in the prevalence and incidence of asthma in the obese arise from this common predisposition. The reader is referred to the article by Litonjua and Gold84 in this issue, where these issues are discussed in depth.

Conclusion

There are several biologically plausible mechanisms that could explain a relationship between obesity and asthma. Further understanding of the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment in this population. Developing such strategies appears warranted because some current asthma treatment modalities are not as effective in the obese patient with asthma.1, 2, 85, 86

References (86)

  • S.A. Shore et al.

    Effect of leptin on allergic airway responses in mice

    J Allergy Clin Immunol

    (2005)
  • N. Guler et al.

    Leptin: Does it have any role in childhood asthma?

    J Allergy Clin Immunol

    (2004)
  • T. Kadowaki et al.

    The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS

    FEBS Lett

    (2008)
  • G. Fantuzzi

    Adiponectin and inflammation: consensus and controversy

    J Allergy Clin Immunol

    (2008)
  • S.A. Shore et al.

    Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

    J Allergy Clin Immunol

    (2006)
  • A.A. Litonjua et al.

    Obesity and asthma: common early life influences in the inception of disease

    J Allergy Clin Immunol

    (2008)
  • L.P. Boulet et al.

    Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma

    Respir Med

    (2007)
  • P. Saint-Pierre et al.

    Are overweight asthmatics more difficult to control?

    Allergy

    (2006)
  • B. Taylor et al.

    Body mass index and asthma severity in the National Asthma Survey

    Thorax

    (2008)
  • K.G. Tantisira et al.

    Association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP)

    Thorax

    (2003)
  • R. Varraso et al.

    Asthma severity is associated with body mass index and early menarche in women

    Am J Respir Crit Care Med

    (2005)
  • D.A. Beuther et al.

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

    Am J Respir Crit Care Med

    (2007)
  • D.A. Beuther et al.

    Obesity and asthma

    Am J Respir Crit Care Med

    (2006)
  • S.A. Shore

    Obesity and asthma: implications for treatment

    Curr Opin Pulm Med

    (2007)
  • S.A. Shore

    Obesity and asthma: lessons from animal models

    J Appl Physiol

    (2007)
  • S.T. Weiss

    Obesity: insight into the origins of asthma

    Nat Immunol

    (2005)
  • R.A. Johnston et al.

    Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone induced pulmonary inflammation

    J Appl Physiol

    (2008)
  • R.A. Johnston et al.

    Augmented responses to ozone in obese carboxypeptidase E-deficient mice

    Am J Physiol Regul Integr Comp Physiol

    (2006)
  • R.A. Johnston et al.

    Allergic airway responses in obese mice

    Am J Respir Crit Care Med

    (2007)
  • W.D. Bennett et al.

    Acute pulmonary function response to ozone in young adults as a function of body mass index

    Inhal Toxicol

    (2007)
  • A. Naimark et al.

    Compliance of the respiratory system and its components in health and obesity

    J Appl Physiol

    (1960)
  • D.J. Ding et al.

    Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

    J Appl Physiol

    (1987)
  • G.G. King et al.

    The effects of body weight on airway calibre

    Eur Respir J

    (2005)
  • R.A. Watson et al.

    Postural changes in lung volumes and respiratory resistance in subjects with obesity

    J Appl Physiol

    (2005)
  • A. Gump et al.

    Relaxation of activated airway smooth muscle: relative potency of isoproterenol vs. tidal stretch

    J Appl Physiol

    (2001)
  • M.G. Sampson et al.

    Load compensation in obese patients during quiet tidal breathing

    J Appl Physiol

    (1983)
  • L.P. Boulet et al.

    Deep inspiration avoidance and airway response to methacholine: Influence of body mass index

    Can Respir J

    (2005)
  • G. Skloot et al.

    Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness

    Clin Rev Allergy Immunol

    (2003)
  • K. Hakala et al.

    Effect of weight loss and body position on pulmonary function and gas exchange abnormalities in morbid obesity

    Int J Obes Relat Metab Disord

    (1995)
  • S. Rorvik et al.

    Lung volumes and arterial blood gases in obesity

    Scand J Respir Dis Suppl

    (1976)
  • G. Hedenstierna et al.

    Airway closure and distribution of inspired gas in the extremely obese, breathing spontaneously and during anaesthesia with intermittent positive pressure ventilation

    Acta Anaesthesiol Scand

    (1976)
  • J. Milic-Emili et al.

    Closing volume: a reappraisal (1967-2007)

    Eur J Appl Physiol

    (2007)
  • A. Taraseviciute et al.

    Severe pulmonary hypertension in postmenopausal obese women

    Eur J Med Res

    (2006)
  • Cited by (0)

    (Supported by an educational grant from Merck & Co., Inc.)

    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

    Supported by National Heart, Lung, and Blood Institute grant HL-084044 and National Institute of Environmental Health Sciences grants ES-013307 and ES-00002.

    Disclosure of potential conflict of interest: S. A. Shore has consulting arrangements with Merck and Schering-Plough.

    Terms in boldface and italics are defined in the glossary on page 1088.

    View full text