Cardiovascular Risk in Asthma

• Author / Creator

  Moore, Linn E

• Introduction: Asthma is a chronic inflammatory disease characterized by intermittent episodes of acute airway inflammation and bronchoconstriction. Although asthma is generally considered a disease of the airways, asthma is also associated with an increased risk of developing cardiovascular (CV) diseases such as coronary artery disease, cerebrovascular disease, and heart failure. The reasons for the increased CV risk in asthma are not well understood; therefore, the purpose of this dissertation was to evaluate different aspects of asthma which may contribute to CV risk: physical inactivity; exertional dyspnea; airway inflammation; and asthma medications. Methods: This dissertation consists of four projects. In Chapter III, to assess the impact of physical activity and fitness on CV health, the endothelial function (flow-mediated dilation (FMD)), microvascular function (velocity time integral (VTI) during reactive hyperemia), and arterial stiffness (pulse wave velocity (PWV)) were evaluated in 16 asthmatics and 16 physical activity and fitness-matched controls. In Chapter IV, the physiological reasons for exertional dyspnea were evaluated in 16 asthmatics and 16 age and sex-matched controls. The participants completed two incremental bicycle exercise tests to exhaustion, and the dyspnea responses (modified Borg (0-10) scale) were evaluated in relation to operating lung volumes. In random order, salbutamol was given prior to exercise to evaluate the impact on the sensory and physiological responses to exercise. In Chapter V, 12 asthmatics completed three bronchial challenge tests (placebo, mannitol, and methacholine) in random order on separate days, and the impact of increased pulmonary inflammation and bronchoconstriction was assessed. Prior to, and within one hour after each bronchial challenge, FMD, VTI, PWV, and systemic inflammation (serum C-reactive protein (CRP)) levels were evaluated. In Chapter VI, FMD, VTI, and PWV were evaluated at baseline and following 400 mcg of inhaled salbutamol or placebo (delivered on separate days, order randomized) in 14 asthmatics and 14 controls. Subsequently, to further examine the systemic vascular differences between asthmatics and controls observed following salbutamol inhalation, the systemic vascular responses to a large sympathetic stimulus (delivered via the cold pressor test (CPT) were evaluated in a subset of 10 asthmatics and 10 controls, and compared to placebo (body temperature water hand submersion). Results: When matched for physical activity and fitness, asthmatics and controls displayed similar endothelial function; however, arterial stiffness remained elevated in asthmatics (PWV: 7.3 m/s vs. 8.7 m/s, p˂0.05). During incremental exercise, asthmatics experienced intensified exertional dyspnea compared to controls, which was explained by reduced inspiratory reserve volume, throughout exercise in asthmatics. Neither the sensation of dyspnea nor the operating lung volumes were affected by salbutamol usage. Both mannitol and methacholine challenges resulted in significant bronchoconstriction (reduction in forced expiratory volume in one second from baseline of 11.5% and 19.3%, respectively), but only the mannitol challenge caused elevated systemic inflammation (CRP levels increased by 60.4% following mannitol, versus -20.6% following methacholine, p<0.05). Neither challenge lead to systemic vascular changes. In the last study, salbutamol inhalation resulted in reduced endothelial function and increased arterial stiffness in asthmatics but not controls (FMD: -3.0% vs. 0.5%, p<0.05, PWV: 0.66 m/s vs. -0.16 m/s, p<0.05 asthmatics vs. controls). Both asthmatics and controls showed similar responses to a non-specific increase in sympathetic nervous activity, indicating that the differences in vascular responses with salbutamol observed in asthmatics were not explained by altered neurovascular transduction. Conclusion: Physical inactivity and reduced fitness levels likely contribute to the increased CV risk seen in stable asthmatics. Asthmatics do show greater exertional dyspnea, and thus to reduce physical activity avoidance, further research should focus on normalizing operating lung volumes during physical activity in asthma. Acutely increasing pulmonary inflammation, but not bronchoconstriction, leads to elevated systemic inflammation and therefore increased CV risk. Furthermore, salbutamol acutely impairs vascular function, and the increased usage of asthma medications during times of reduced asthma control likely contributes to elevated CV risk.

• Subjects / Keywords

  • Asthma
  • Cardiovascularvascular
  • Exercise

• Graduation date

  Spring 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3959CP66

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.