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Effect of Exercise on Drug Therapy and Respiratory Disease

Pulmonary rehabilitation and its use in combination with current drug treatments - Iain Mactier

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder (Stav et al. 2009). It is characterised by chronic, non-reversible airway obstruction (Theander et al. 2009). Those with COPD experience reduced exercise capacity and difficulties with daily activities (Peters et al. 2006, Cukier et al. 2007, Stav et al. 2009). As a result, patients with COPD will often unconsciously adopt a sedentary lifestyle, the resulting physical deconditioning marking the start of a vicious circle, leading to further sedentarism and increased risk of co-morbidities (ZuWallack et al. 2008).

Pulmonary rehabilitation (PR) programs aim to minimise the impairment and health implications of COPD, through exercise training and health education (Theander et al. 2009). A higher level of physical activity has been shown to decrease hospital admissions, for all causes, in COPD patients (Garcia-Aymerich et al. 2009). This abstract explores the benefit of pulmonary rehabilitation, and investigates its potential use in combination with current drug treatments such as bronchodilators and supplemental oxygen.

Garcia-Aymerich et al. (2009) sought to explore the mechanisms through which regular exercise benefits COPD patients. 341 COPD patients had their level of physical activity assessed, along with a number of variables indicative of respiratory decline. Higher levels of physical activity were positively correlated with lower levels of systemic inflammatory markers such as C-reactive protein (CRP) (p=0.036), a higher diffusing capacity of the lung for carbon monoxide (DLCO) (p<0.01), and increased six minute walking distance (6MWD) (p=0.006). Trends for increased respiratory muscle strength and VO2 max were also noticed in more active patients. Theander et al. (2009) were able to show improvements in functional status in COPD patients engaged in PR. 30 patients were assigned to either the PR group who trained at least twice weekly, or a control group. Those assigned PR demonstrated a significant mean increase of 40.6 ± 27.2 m in 6MWD (p<0.05), though this is less than the value estimated to be a clinically relevant increase in 6MWD (~54m) (Cukier et al. 2007). It could be that this study was too short and clinically significant improvements may have been observed if training was continued for longer. However, when patients receiving PR expressed their own functional difficulties with daily activities, performance (p<0.01) and satisfaction (p<0.001) were both significantly improved over the 12 weeks. This would likely lead to an improvement in quality of life for those patients. Stav et al. (2009) looked at the effects of PR on functional status in 80 COPD patients over a longer time span of 3 years. Maximum sustained cycle time was significantly increased over this time, from 6 ± 1.1 minutes in control trials, to 11.8 ± 4 minutes (p<0.01). A significant reduction in the decline in forced expiratory volume in one second (FEV1) in the PR group was also observed (p<0.001) suggesting PR may slow the disease progression of COPD.

Drug treatments may increase the effectiveness of PR by allowing the exercise training to occur at a higher intensity (ZuWallack et al. 2008). Peters et al. (2006) investigated the effectiveness bronchodilators (nebulised salbutamol 2.5mg + 500µmg ipratropium bromide) and supplemental oxygen (bag reservoir, 50% O2) on exercise capacity, both alone and in combination, in relieving exertional dyspnoea, and on exercise endurance times. 16 COPD patients were evaluated. Exercise endurance was significantly increased in the combination therapy group compared to either solo treatment or controls (p<0.05). During the symptom limited, constant load cycle, dyspnoea experienced decreased with all interventions (p<0.05). Significantly fewer subjects receiving the combined treatment stopped the exercise due to dyspnoea, instead finding leg discomfort or other issues the limiting factor (p<0.01). 

Using a similar three treatment regimes, Cukier et al. (2007) also sought to evaluate the effect of bronchodilators (nebulised salbutamol 5mg + 500µmg ipratropium bromide) and supplemental oxygen (delivered by nasal prongs, 3l/min) on exercise capacity. 6MWD increased significantly in response to all three treatment regimes (p<0.05 – 0.0001). 28 COPD patients were evaluated and the greatest increase in exercise capacity was observed following combination therapy, with 19/28 (68%) improving their 6MWD greater than the clinically relevant threshold of 54m.

Pulmonary rehab benefits the health and functional status of COPD patients (Stav et al. 2009, Theander et al. 2009). The benefits of pulmonary rehabilitation often add to the improvements obtained by drug therapies such as bronchodilators and supplemental oxygen (ZuWallack et al. 2008). These same drug therapies appear to improve patients exercise ability, suggesting they may have a role in enhancing the effectiveness of PR exercise training (Peters et al. 2006, Cukier et al. 2007). The optimal dose of drugs to produce this effect is unclear and would benefit from further research.

  • Cukier, A., Ferreira, C.A.S., Stelmach, R., Ribeiro, M., Cortopassi, F. & Calverley, P.M.A. 2007, "The effect of bronchodilators and oxygen alone and in combination on self-paced exercise performance in stable COPD." Respiratory medicine, vol. 101, no. 4, pp. 746.
  • Garcia-Aymerich, J., Serra, I., Gmez, F., Farrero, E., Balcells, E., Rodrguez, D., de Batlle, J., Gimeno, E., Donaire-Gonzalez, D., Orozco-Levi, M., Sauleda, J., Gea, J., Rodriguez-Roisin, R., Roca, J., Agust, A. & Ant, J. 2009, "Physical activity and clinical and functional status in COPD." Chest, vol. 136, no. 1, pp. 62.
  • Peters, M.M., Webb, K.A., O'Donnell, D.E. 2006, "Combined physiological effects of bronchodilators and hyperoxia on exertional dyspnoea in normoxia COPD." Thorax, vol. 61, pp. 559-567
  • Stav, D., Raz, M. & Shpirer, I. 2009, "Three years of pulmonary rehabilitation: inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease." BMC Pulmonary Medicine, vol. 9, pp. 26.
  • Theander, K., Jakobsson, P., Jorgensen, N. & Unosson, M. 2009, "Effects of pulmonary rehabilitation on fatigue, functional status and health perceptions in patients with chronic obstructive pulmonary disease: a randomized controlled trial." Clinical rehabilitation, vol. 23, no. 2, pp. 125-136.
  • ZuWallack, R.L. 2008, "The roles of bronchodilators, supplemental oxygen, and ventilatory assistance in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease." Respiratory care, vol. 53, no. 9, pp. 1190-1195.


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