updated 7/21/2008
OBESITY AND ASTHMA: POSSIBLE MECHANISMS
Stephanie Shore PhD writes in Journal of Allergy Clinical Immunology Volume 121, Issue 5 (May 2008) -
The relationship between obesity and asthma has not been established, but mechanical factors, aspects of the systemic inflammation related to obesity including changes in energy-regulating hormones, comorbidities of obesity, or common etiologies may contribute
Mechanistic factors:
the functional residual capacity (FRC) is reduced
Breathing at low lung volume has been shown to increase airway responsiveness.
The observation that deep inspiration has a reduced bronchodilatory effect in obese versus lean individuals supports the hypothesis that the airways of the obese are stiff and not easily expanded by lung inflation. A similar reduced bronchodilatory effect of a deep breath is observed in asthma.
Small airway closure is observed in many obese subjects during tidal breathing, particularly in the supine posture
Chronic systemic inflammation
It is now well established that obesity is a state of chronic low-grade systemic inflammation.
It is generally believed that this inflammation spills over into the blood, leading to inflammatory activation at sites distant to the adipose tissue. Adipokins have been shown to have pro-inflammatory effect. Others serum factors that are elevated in obesity may derive from effects of these adipokines on the vasculature. Elevated levels of many adipokines are observed in the serum in proportion to the BMI and have been shown to correlate with type 2 diabetes and atherosclerosis.
Adipokines such as IL-6, TNF-?, plasminogen activator inhibitor 1, eotaxin, vascular endothelial growth factor (VEGF), and monocyte chemotactic protein (MCP)–1, have been associated with asthma and could play a role in the relationship between obesity and asthma
Levels of 8-isoprostane and other markers of oxidative stress are increased both in the blood and the lungs of obese versus lean patients with asthma and may also contribute to the relationship between obesity and asthma.
Energy-regulating hormones
Two cross-sectional studies have reported higher serum leptin in patients with asthma, but both indicate that this association is observed independent of obesity. Thus, it is conceivable that leptin does increase the risk of asthma.
Alternatively, inflammation, including asthmatic-type inflammation can induce the release of leptin from adipocytes. Hence, it is conceivable that the association between asthma and leptin is the result of leptin release stemming from systemic manifestations of asthmatic airway inflammation.
In contrast with other adipokines, adiponectin, an insulin-sensitizing hormone, declines in obesity.
Adiponectin also has important anti-inflammatory effects in obesity. Lac of this may increase the likelihood of developing inflammatory diseases like asthma.
Authors have shown have shown that in mice, exogenous administration of adiponectin results in an almost complete suppression of allergen-induced AHR, airway inflammation, and TH2 cytokine expression in the lung.[
Comorbidities
A recent study indicated a higher prevalence of asthma in children with high serum cholesterol.
GERD and SDB are known to increase the risk for asthma,
although the data suggest that insulin resistance could contribute to the obese asthmatic phenotype, it is also possible insulin resistance stems from the same type of systemic inflammation that also leads to asthma
As proposed by others, 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.
It is i extremely important not to overlook the role of obesity in aggravating asthma.
UPDATED 7/20/08
