Abstract
Introduction: Obesity and asthma are both increasingly common conditions. It is thought that those who are obese have a greater predisposition to develop asthma but the mechanisms for this are poorly understood. It is possible that pro-inflammatory cytokines associated with obesity are implicated in the pathogenesis of asthma, but there are little data to support this. Furthermore, respiratory function is impaired in obesity, but the precise mechanical effect of obesity is difficult to identify.
Aims: 1) To explore the inflammatory association between obesity and asthma 2) To determine whether there are differences in acute bronchoconstriction between obese and non-obese asthmatics 3) To explore the effect of the regional distribution of body fat on respiratory function 4) To determine the effect of marked weight loss on respiratory function.
Methods: Through clinical studies based at the Otago Respiratory Research Unit and epidemiological data from the Dunedin Multidisciplinary Health and Development Study, seven studies were undertaken.
Seventy-nine individuals with asthma and without asthma were recruited. After steroid withdrawal, fasting blood and induced sputum were collected for the measurement of a range of cytokines. Interactions between systemic inflammation and airway inflammation were explored. A further thirty asthmatics with a range of weight underwent a methacholine challenge to determine differences in lung volume after bronchoconstriction.
One hundred and seven men and women without respiratory disease were recruited to explore the effect of adiposity measured by dual-energy x-ray absorptiometry on respiratory function. The individual contribution of thoracic and abdominal fat was measured. In the fourth clinical study, differences between respiratory function and dyspnoea were explored following weight loss induced by gastric volume reduction.
Data from the Dunedin Study was used to explore the association between exhaled nitric oxide as a measure of airway inflammation, and c-reactive protein and fibrinogen, as nonspecific measures of systemic inflammation. Further data explored the association between blood leptin, adiponectin and a number of measures of the asthma phenotype.
The association between adiposity measured by bio-electrical impedance and a full range of standard respiratory function tests was also explored.
Results: No association between the systemic inflammation of obesity and the airway inflammation of asthma was found. In the study investigating changes following acute bronchoconstriction, the increases in functional residual capacity were greater in obese asthmatics.
The majority of respiratory function parameters were significantly associated with total body fat measured by dual-energy x-ray absorptiometry and the regional contributions of thoracic and abdominal adiposity were similar. Weight loss induced by gastric volume reduction resulted in significant improvements in respiratory function and the perception of dyspnoea.
Conclusion: There was no evidence to support the hypothesis that the association between obesity and asthma is driven by inflammation. The effect of adiposity may be mechanical rather than inflammatory. Obese individuals experience more dynamic hyperinflation following bronchoconstriction, which may help to explain differences in asthma severity in obese asthmatics.
Thoracic and abdominal adiposity appear to contribute to a similar degree to the impairment in respiratory function in the obese, and weight loss induced by gastric volume reduction results in significant improvements in measures of dyspnoea and respiratory function.