The Study on Obesity and Asthma

Obesity and asthma has been two increasing health issues that are more and more important as the global epidemic of obesity became a major public health problem. Whether obesity is a major risk factor in certain respiratory diseases is still controversial, such as in airway hyperresponsiveness or asthma. However, its contributory role in related diseases has gain more focus recently. Therefore, we would like to explore the interactions between obesity and asthma, and elaborate the weight of its role, and possibly their mechanism.
Therefore this thesis established the whole project to include two specific arms.
The first arm is a cross sectional study on a large population survey in children to clarify the role of obesity on asthma on a huge population, that is relatively healthy children. Childhood asthma, a growing health concern, has been associated with low birth weight and elevated body mass indices (BMIs). This study tested the hypothesis that overweight and obese adolescents with a history of low birth-weight are at even greater risk of developing asthma. A cohort of 75,871 junior high school students was screened for asthma during 1995 Oct-1996 Mar in Taiwan. Birth weight and estimated gestational age were obtained from the birth registry. Logistic regression and simple regression analyses were adjusted for confounding variables. Asthma was more prevalent in those with birth weights below 3,000 g and higher adolescent BMIs. Furthermore, those with both characteristics were consistently most likely to have asthma. Whether the asthma diagnosis among low birth weight subjects was assigned by physicians (PD) or medical questionnaire (MQ), the odd ratios were elevated for both overweight (PD: 1.41; MQ: 1.25) and obese (PD: 1.38; MQ: 1.47) boys as well as overweight (PD: 1.63; MQ: 1.30) and obese (PD: 1.44; MQ: 1.32) girls (P < 0.05). Low birth weight predisposes one to develop asthma and excess body mass amplifies the risk. A sex difference was observed. This study suggests prenatal care and nutrition counseling may reduce asthma prevalence.
The second arm is a basic research study, utilizing an animal model to explore the relationship between obesity and airway hyperresponsiveness, and whether inflammation plays any specific role in their relationship. Epidemiological studies indicate the incidence of asthma is increased in obese and over-weight humans. Responses to ozone (O3), an asthma trigger, are increased in obese (ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-Rb) is required for satiety; mice lacking this receptor (db/db mice) are also substantially obese. Here, wild type and db/db mice were exposed to air or O3 (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than wild type mice after air exposure. O3-induced increases in pulmonary resistance and airway responsiveness were also greater in db/db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O3 exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O3 was significantly greater in db/db than wild type mice. Previously published results obtained in ob/ob mice were similar except for O3-induced neutrophils and MIP-2, which were not different from wild type mice. O3 also induced pulmonary IL-1beta and TNF-alpha mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-Ra) was similar in db/db and wild type mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O3. Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-Rb but not Ob-Ra, suggest leptin, acting through Ob-Ra, can modify some pulmonary responses to O3.
As for summary, two specific study arms show important information for clarifying the relationship between obesity and asthma. Epidemiologic study reveals that obese increases the risk of asthma, and this effect is more prominent when the body weight gain increase to overweight and obese at teenage since being born as low birth weight babies. Animal experiments further elaborates that db/db obese mice lacking the leptin receptor, which produces exaggerated airway hyper-responsiveness constriction, and its mechanism has involved tumor necrosis factor TNF-alpha as an inflammation role. These results provide us more clues about the characteristics of obese-induced asthma, and need further more research to settle down specific preventive and treatment modalities for this type of asthma.