The relationship between lung mechanics and breathlessness in chronic obstructive pulmonary disease.
2015-11-19T08:51:14Z (GMT) by
Breathlessness and limited exercise tolerance are the principal symptoms of COPD. Bronchodilator therapy is directed towards the relief of these disabling symptoms but little is known of the mechanism of relief of dyspnoea or which tests best predict symptomatic benefit from bronchodilator. This thesis examines the appropriateness of a range of radiological and physiological tests in assessing disease severity and the symptomatic benefit derived from bronchodilators and examines the physiological mechanisms which result in reduced dyspnoea following their use. The estimation of lung volume radiographically was disappointing and was only comparable with other methods for group data. Agreement within individual patients was poor. My data suggests that radiological measures of lung volume are unsuitable for individual patient studies but it may still be useful in retrospective epidemiological studies where other lung volume data is not available. Inhaled oxitropium bromide and nebulised salbutamol both improved 6 minute walking distance, the improvement in exercise capacity being independent of improvements in FEVl or FVC. Resting breathlessness was significantly improved by both oxitropium and salbutamol, whilst end of walk breathlessness was improved following oxitropium. Both these measures of improvement were independent of spirometric improvement. However increases in peak inspiratory flow rate after oxitropium bromide correlated significantly with improvements in end of walk breathlessness. Improvements in breathlessness and walking distance were not explained by reductions in lung volume measured either by helium dilution or body plethysmography. Trapped gas volume proved to be an unreliable measurement and had no value in the prediction of functional benefit from bronchodilator. Large falls in resting airways resistance occured in these COPD patients following oxitropium bromide. The falls in airways resistance occurred independently of improvements in spirometry but were not quantitively related to improvements in either breathlessness or 6 minute walking distance. Mouth occlusion pressure was not a correlate of resting breathlessness neither did changes in PO.l correlate with reductions in breathlessness. The presence of severe airflow obstruction and PEEPi make the measurement of mouth occlusion pressure suspect in these patients. Oxitropium bromide caused a small fall in resting oxygen saturation, salbutamol had no effect on resting saturation. Corridor walking exercise produced brisk falls in oxygen saturation, but the severity of desaturation was unaffected by the bronchodilator. Recovery from desaturation at the end of the walk was rapid. Histamine challenge increased breathlessness but alterations in levels of breathlessness were not correlated with the increases in end expiratory lung volume provoked by the challenge. Oxitropium bromide reduced positive end expiratory pressure (PEEPi), respiratory accessory muscle activity and reduced pleural pressure swings during hypoxia and hypercapnia stimulated breathing. Thus the efficiency of ventilation was improved by their inhaled bronchodilator. There was no difference in the rate of change of breathlessness with increasing ventilation between isocapnic hypoxaemic and progressive hypercapnic stimulated breathing. In conclusion an anticholinergic bronchodilator can improve exercise capacity and breathlessness, independent of changes in conventional lung function tests or alterations in oxygen saturation. Alterations in these measurements which relate to dynamic changes occuring during respiration such as PEEPi, accessory muscle activity and pleural pressure swings may be more useful in assessing the response to bronchodilator drugs.