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P266 Do endothelin-1 and inflammation play a role in airway obstruction in pulmonary arterial hypertension associated with congenital heart disease?
  1. AT Low1,
  2. SJ George2,
  3. AB Millar2,
  4. RMR Tulloh1
  1. 1University Hospitals Bristol, Bristol, UK
  2. 2University of Bristol, Bristol, UK

Abstract

Introduction Airway obstruction has been demonstrated in patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease (CHD-APAH), but the cause is unknown. The vasoactive mediator endothelin-1 is a potent vasoconstrictor that induces smooth muscle proliferation in pulmonary arterial hypertension. Endothelin-1 also has the potential to cause bronchoconstriction when present in the airways, though this has not been demonstrated in CHD-APAH. Systemic inflammation also occurs in CHD-APAH but associated airway inflammation has not been investigated. This study investigates the relationship between inflammation, endothelin-1 and airway dysfunction in CHD-APAH patients.

Methods 58 patients were prospectively recruited: 20 CHD-APAH, 20 CHD and 18 healthy controls. Exclusion criteria were pre-existing lung disease, significant smoking history, scoliosis and Down’s syndrome. Participants performed full lung function tests and provided serum and induced sputum samples at a single visit. Serum and sputum cytokines were measured by multiplex bead assay array and endothelin-1 levels measured by enzyme linked immunosorbent assay. Induced sputum was also assessed for total and differential cell counts.

Results Serum cytokines and endothlin-1 levels were significantly elevated in patients with CHD-APAH in comparison to CHD and healthy controls (See Table 1). There were no significant differences in sputum cytokine or endothelin-1 levels between the 3 groups, with no differences in total or differential cell counts. A significant correlation between serum endothelin-1 levels and FEF25–75 was found for CHD-APAH patients (r = -0.6017, p = 0.0083 Spearman). There were no significant correlations between measures of airway obstruction and serum cytokine levels.

Abstract P266 Table 1

Serum and induced sputum cytokine and endothelin-1 levels for CHD-APAH patients, CHD patients and healthy controls

Conclusions There is evidence of systemic inflammation in CHD-APAH patients but serum cytokines did not correlate with measures of airway dysfunction, and there was no evidence of airway inflammation. This suggests that inflammation does not play a role in airway obstruction in this patient group. Serum endothelin-1 is significantly elevated in CHD-APAH patients, and this did correlate with measures of airway obstruction. While elevated endothelin-1 in the pulmonary vessels may affect the adjacent airways, induced sputum endothelin-1 was not elevated. Whether serum endothelin-1 can cause bronchoconstriction without being associated with raised levels in the airways is unclear and requires further investigation.

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