Doctor of Philosophy(PhD) / Over the last 20 years both asthma and obesity have increased in prevalence. What is the link? There are data to suggest that increasing obesity is a risk for the increase in prevalence of asthma. A number of mechanisms have been postulated including the effects of reduced lung volume on bronchial reactivity and mechanical changes with lower lung volumes. Other possibilities include other obesity-induced co-morbidities including gastro-oesophageal reflux. The aim of this thesis was to evaluate the link between asthma and obesity in both adult and childhood populations and to undertake experimental studies to examine the effects of changes in lung volume on bronchial reactivity. In chapter 1, the literature is reviewed. The current literature suggests that there is a link between diagnosis of asthma, new onset of asthma, symptoms of shortness of breath and wheeze. In chapter 2, data on 1997 adults in 3 population studies were analysed and the association between body mass index (BMI) and symptoms of shortness of breath and wheeze, diagnosis of asthma, medication usage for asthma, lung function and bronchial responsiveness were studied. This study showed that obesity was a risk for recent asthma (OR 2.04; 95%CI 1.02-3.76, p=0.048), symptoms of shortness of breath and wheeze (OR 2.6; 95%CI 1.46- 4.70, p=0.001), and medication usage for asthma (OR 2.53; 95%CI 1.36-4.70, p=0.003). There was a reduction in lung volume as measured by forced vital capacity (FVC), but there was no increase in bronchial hyperresponsiveness (BHR) (OR 0.87; 95% CI 0.35-2.21, p=0.78). Thus although the symptoms of asthma are increased there were no increases in BHR, despite significantly reduced lung volumes. The increase the medication usage is unlikely to have normalised the BHR, as there were ongoing symptoms suggestive of asthma. In chapter 3, data on 5993 children in 7 population studies were analysed and the association between BMI percentile and symptoms of cough, wheeze, ix diagnosis of asthma, medication usage for asthma, atopy, lung function and bronchial responsiveness was studied. After adjusting for atopy, sex, age, smoking and family history, BMI was a significant risk factor for wheeze ever (OR=1.06; 95%CI 1.01-1.10, p=0.008) and cough (OR=1.09; 95%CI 1.05-1.14, p=0.001) but not for recent asthma (OR=1.02; 95%CI 0.98-1.07 p=0.43), or bronchial hyperresponsiveness (OR=0.97; 95%CI 0.95-1.04 p=0.77). In girls, a higher BMI was significantly associated with higher prevalence of atopy (x2 trend 7.9, p=0.005), wheeze ever (x2 trend 10.4, p=0.001), and cough (x2 trend 12.3, p<0.001). These were not significant in boys. With increasing BMI in children, there was no reduction in lung volume, no increase in airway obstruction and no increase in bronchial responsiveness. In chapter 4, the hypothesis that obesity per se is associated with bronchial responsiveness was tested. Six obese women without asthma were compared to 6 non-obese women without asthma with high dose methacholine challenges to assess the bronchial responsiveness. There was no increase in bronchial responsiveness, and no difference in the position or shape of the high dose methacholine curve despite the fact that these women had reduced lung volumes associated with their obesity. In chapter 5, the hypothesis whether reduced lung volume per se would cause a change in greater mechanical effect, ie more marked airway narrowing in both non-asthmatic and asthmatic subjects was tested. Lung volumes and methacholine challenges were undertaken in the supine and erect position on different days. As expected in normal subjects there was a small reduction in lung volume on lying down, this was associated with an increase in the measure of bronchial reactivity DRR. In contrast, in asthmatics, there was no acute fall in lung volume and there were variable changes in the index of reactivity suggesting non-homogeneity in the lung function abnormality. This suggests changes in bronchial reactivity can occur without any relationship to lung volume change. These negative results suggest that lung volume changes that may occur in obesity are unlikely contributors to the apparent increase in asthma symptoms. In chapter 6, the hypothesis that the supposed increase in asthma symptoms in the obese were due to the effects of gastro-oesophageal reflux were assessed in 147 obese subjects graded for gastro-oesophageal reflux severity using manometry and gastroscopy. This study showed that subjects with increased gastro-oesophageal reflux did not have subjective increases in asthma prevalence, obstructive sleep apnoea, or snoring however they had a clear worsening of gas transfer as measured by carbon monoxide transfer suggesting a greater level of parenchymal disease. The overall results are that there is an increase of diagnosis of asthma, increase in symptoms of asthma and medication usage for the treatment of asthma in the obese. Objectively despite reductions in lung volume, there is no increase in bronchial responsiveness in this group suggesting that these symptoms are not related to true asthma, but to alternative co-morbidities associated with obesity such as gastro-oesophageal reflux. Notably gastrooesophageal reflux was not associated with increased asthma prevalence or airway obstruction. However it was associated with reduced gas transfer suggesting parenchymal disease. This suggests that the increase in symptoms of wheeze and shortness of breath in the obese should not be attributed to asthma in the absence of variable airflow limitation that is reversible spontaneously or with treatment, or with an increase in the existing bronchial hyperresponsiveness (BHR) to a variety of stimuli.
| Identifer | oai:union.ndltd.org:ADTP/232755 |
| Date | January 2005 |
| Creators | Schachter, L. M |
| Publisher | University of Sydney., Discipline of Medicine |
| Source Sets | Australiasian Digital Theses Program |
| Language | en_AU |
| Detected Language | English |
| Rights | The author retains copyright of this thesis., http://www.library.usyd.edu.au/copyright.html |
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