Reviews and feature articleObesity and asthma: Possible mechanisms
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
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(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.