Effects of xanthine oxidase inhibitors in pulmonary hypertension associated with chronic lung disease

Chronic lung diseases are often complicated with pulmonary hypertension (PH). This can lead to disability and poor prognosis. Oxidative stress has been implicated in the development of PH and right ventricular hypertrophy (RVH).A possible new way to treat lung disease related pulmonary hypertension is allopurinol (a xanthine oxidase inhibitor) which decreases both uric acid and oxidative stress. We hypothesised that allopurinol could regress RVH in patients with pulmonary hypertension associated with chronic lung disease (PH-CLD).In a double-blind, randomised controlled clinical trial, 72 patients with PH-CLD (93% diagnosed with chronic obstructive pulmonary disease and 17% with interstitial lung disease) were randomised to receive either allopurinol 300 mg twice daily or placebo for twelve months. The primary outcome was the mean change in right ventricular mass (RVM) as assessed by cardiac magnetic resonance imaging (CMRI) at twelve months. The secondary outcomes were the change in other cardiac parameters measured by CMRI, St George’s Respiratory Questionnaire, Short Form 36, spirometry and six-minute walk test (6MWT).The mean age was 71 years, the mean FEV1 was 60% with mean resting SaO2 of 96%. After 12 months, there was no significant change in RVM. There were also no significant changes in other cardiac parameters measured on CMRI, quality of life questionnaires, spirometry and 6MWT. Post-hoc subgroup analysis showed that allopurinol reduced RVM (allopurinol -6.16 g vs placebo 0.75 g, p = 0.02) in COPD patients with more severe airflow limitation. Patients with higher NT-proBNP (> 489 pg/ml) had a greater improvement in left ventricular ejection fraction with allopurinol 5.12 vs placebo -1.62, p = 0.02.In summary, allopurinol had no overall impact but reduced RV mass in COPD patients with more severe airflow limitation. Further studies are warranted to assess the longer term impact of allopurinol in more severe COPD.

Name dc:type.qualificationname

Doctor of Medicine

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2019

Author dc:creator

• Liu Shiu Cheong, Patrick

Advisors dc:contributor.advisor

• Struthers, Allan
• Lipworth, Brian

• COPD
• pulmonary hypertension
• right ventricle
• Allopurinol
• ILD

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/ee8678d8-e7c7-498c-b501-ff5522f32ae5

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/ee8678d8-e7c7-498c-b501-ff5522f32ae5