The Effect of Asthma on Systemic Inflammation, Oxidative Stress and Cardiovascular Morbidity
Condition: Asthma
MeSH terms: Asthma; Inflammation
Study type: Observational

Summary: 
      Asthma is a chronic airway inflammation which involves the interplay of different types of
      inflammatory cells and cytokines in the airway. The presence of systemic inflammation and
      oxidative stress in asthma suggests that it has a propensity to develop cardiovascular
      morbidity. Recent small scale studies have demonstrated that asthma severity may be
      associated with both airway and systemic inflammation. The investigators' study aims at
      linking asthma severity to airway and systemic inflammation, and subsequently to
      cardiovascular morbidity if a significant association of the aforementioned is present. The
      role of airway inflammation in contribution to systemic inflammation , and potential
      interaction between these two conditions will also be studied.
    

Detailed description: 
      Asthma is a chronic inflammatory airway disorder, associated with airflow obstruction and
      bronchial hyper-responsiveness, which affects about 10% of population in Hong Kong. It has
      been a major respiratory disease in Hong Kong that carries significant morbidity and high
      hospitalization burden in all ages. The use of long-term inhaled corticosteroid treatment in
      recent decades has become the cornerstone in the treatment of most patients with persistent
      asthma with reduction in its mortality. The ultimate goal of treatment is to achieve optimal
      control of airway inflammation and asthma-related mortality and morbidity.

      In recent studies on the evaluation of airway and systemic inflammation in patients with
      asthma, various biomarkers have been measured in exhaled breath condensate (EBC), like nitric
      oxide, nitrates/nitrites and 8-isoprostane. Similarly, measurement of biomarkers in blood,
      notably high-sensitivity c-reactive protein (hs-CRP), 8-isoprostane and antioxidants
      (catalase, superoxide dismutase, glutathione peroxidase, glutathione), has also been used to
      reflect the levels of systemic inflammation and oxidative stress.

      There has been substantial evidence from landmark epidemiological studies in the past 10
      years, predominantly based on plasma hs-CRP, that chronic low grade systemic inflammation is
      an independent predictor for the development of hypertension, myocardial infarction, stroke,
      cardiovascular death and peripheral vascular disease. A dose-dependent risk association
      between hs-CRP and these cardiovascular morbidities has also been consistently demonstrated.
      Moreover, there has been overwhelming data to suggest the association between oxidative
      stress and the development cardiovascular disease. This association is easily understood in
      light of the cellular damages and endothelial dysfunction due to oxidative stress, which may
      lead to the development of atherosclerosis and cardiovascular morbidity.

      In chronic obstructive pulmonary disease (COPD), a chronic inflammatory airway disorder
      characterized by irreversible airflow obstruction induced mainly by tobacco smoking, studies
      have demonstrated that, in acute exacerbations of COPD and smoking, there is a marked
      imbalance of redox status. The increased oxidative stress results in the inactivation of
      alveolar antiproteases, airspace epithelial damage, increased influx of neutrophils into lung
      tissue and the expression of pro-inflammatory mediators. Similarly, patients with COPD also
      have increase neutrophils, lymphocytes and TNF-α in the peripheral blood. In fact, many
      studies have demonstrated the existence of low grade systemic inflammation and oxidative
      stress in patients with COPD. Important studies published in recent 5 years have also linked
      the elevation of these systemic biomarkers, in a dose-dependent manner, to COPD severity and
      increased prevalence of cardiovascular and cerebrovascular morbidity and mortality in
      patients with COPD.

      On the other hand, chronic airway inflammation is also the hallmark of asthma which involves
      the interplay of different types of inflammatory cells, including T-lymphocytes, eosinophils,
      neutrophils, macrophages and cytokines in the airway. Although the pathogenesis of asthma is
      incompletely understood, studies have shown that it is associated with a state of increased
      free radical formation, because cells derived from airways and peripheral blood of patients
      with asthma generate increased amount of reactive oxygen species, the level of which is
      related to severity of asthma. Besides, airway biomarkers indicating airway inflammation and
      oxidative stress have been consistently shown to be positively related to asthma severity and
      asthma control, which can be alleviated with treatment by inhaled corticosteroids.
      Additionally, recent preliminary studies have indicated that, apart from the presence of
      chronic airway inflammation (elevated EBC nitric oxide, EBC nitrites/nitrates and EBC
      8-isoprostane), asthma may also be associated with chronic low grade systemic inflammation
      (elevation of plasma hs-CRP) and increased oxidative stress (increased 8-isoprostane; altered
      erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione).

      Whether the presence of systemic inflammation and oxidative stress in asthma is actually a
      consequence of "overspill" of uncontrolled airway inflammation or the existence of an
      extrapulmonary source of inflammation remains unknown. At the moment, there is only little
      evidence on the correlation of airway and systemic inflammation in asthma, as well as the
      relation of systemic inflammation and oxidative stress to asthma severity. Intuitively, as in
      COPD, asthma-related systemic inflammation may as well increase the propensity for
      development of cardiovascular and cerebrovascular diseases. However, there is also a lack of
      study that describes the risk of cardiovascular outcomes of asthma-related systemic
      inflammation and oxidative stress.

      Therefore, we conduct the current study with the primary objective to investigate the
      association of asthma severity with systemic inflammation and oxidative stress, and its
      effect on the risk of various cardiovascular morbidities. The secondary objective is to
      correlate airway inflammation and oxidative stress with systemic inflammation and oxidative
      stress in stable asthmatics.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Asthma patients will be recruited from asthma clinics of 4 centres in Hong Kong, including
        Queen Mary Hospital, Queen Elizabeth Hospital, Kowloon Hospital and Kwong Wah Hospital.
      
Biospecimen description: 
      Plasma, serum, DNA and exhaled breath condensate
    
Keywords: Asthma; Systemic inflammation; Oxidative stress; Cardiovascular morbidity; Airway inflammation