Images in Allergy and Immunology

Obesity, allergy and immunology

Current evidence supports a role for gut colonization in promoting and maintaining a balanced immune response in early life. An altered or less diverse gut microbiota composition has been associated with atopic diseases, obesity, or both. Moreover, certain gut microbial strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. However, there has been no fully adequate longitudinal study of the relation between the neonatal gut microbiota and the development of allergic diseases (eg, atopic asthma) and obesity. The emergence of promising experimental studies has led to several clinical trials of probiotics (live bacteria given orally that allow for intestinal colonization) in human subjects. Probiotic trials thus far have failed to show a consistent preventive or therapeutic effect on asthma or obesity. Previous trials of probiotics have been limited by small sample size, short duration of follow-up, or lack of state-of-the art analyses of the gut microbiota. Finally, there is emerging evidence that the vitamin D pathway might be important in gut homeostasis and in signaling between the microbiota and the host. Given the complexity of the gut micriobiota, additional research is needed before we can confidently establish whether its manipulation in early life can prevent or treat asthma, obesity, or both.

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.

Obesity is an important public health problem. An increasing body of data supports the hypothesis that obesity is a risk factor for asthma. These data include numerous large cross-sectional and prospective studies performed in adults, adolescents, and children throughout the world. With few exceptions, these studies indicate an increased relative risk of asthma in the obese and overweight and demonstrate that obesity antedates asthma. Obesity appears to be a particularly important issue for severe asthma. Studies showing improvements in asthma in subjects who lose weight, as well as studies showing that obese mice have innate airway hyperresponsiveness (AHR) as well as increased responses to certain asthma triggers also suggest a causal relationship between obesity and asthma. The mechanistic basis for this relationship has not been established. It may be that obesity and asthma share some common etiology, such as a common genetic predisposition, common effects of in utero conditions, or that obesity and asthma are both the result of some other predisposing factor such as physical activity or diet. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastroesophageal reflux, complications from sleep-disordered breathing (SDB), breathing at low lung volume, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population.

This year we present updates on the management and therapeutics of asthma and research on the relationship of airway remodeling to clinically irreversible disease and continue a discussion about the origins of asthma. Significant advances are occurring in our understanding of the natural history of asthma, including the application of biomarkers and genetics. These tools should assist the clinician in defining patients at risk for significant morbidity related to asthma. Incorporating this knowledge will help prompt the development of more effective management techniques and new medications. Meanwhile, more effective health care strategies must be developed to reduce the reported disparities in asthma care noted in our patient populations.