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.

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.