Projects per year
Bronchiectasis is characterised by chronic cough, sputum production, and recurrent chest infections. Pathogenesis is poorly understood, but excess neutrophilic airway inflammation is seen. Accumulating evidence suggests that statins have pleiotropic effects; therefore, these drugs could be a potential anti-inflammatory treatment for patients with bronchiectasis. We did a proof-of-concept randomised controlled trial to establish if atorvastatin could reduce cough in patients with bronchiectasis.
Patients aged 18-79 years were recruited from a secondary-care clinic in Edinburgh, UK. Participants had clinically significant bronchiectasis (ie, cough and sputum production when clinically stable) confirmed by chest CT and two or more chest infections in the preceding year. Individuals were randomly allocated to receive either high-dose atorvastatin (80 mg) or a placebo, given orally once a day for 6 months. Sequence generation was done with a block randomisation of four. Random allocation was masked to study investigators and patients. The primary endpoint was reduction in cough from baseline to 6 months, measured by the Leicester Cough Questionnaire (LCQ) score, with a lower score indicating a more severe cough (minimum clinically important difference, 1.3 units). Analysis was done by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT01299181.
Between June 23, 2011, and Jan 30, 2011, 82 patients were screened for inclusion in the study and 22 were excluded before randomisation. 30 individuals were assigned atorvastatin and 30 were allocated placebo. The change from baseline to 6 months in LCQ score differed between groups, with a mean change of 1.5 units in patients allocated atorvastatin versus -0.7 units in those assigned placebo (mean difference 2.2, 95% CI 0.5-3.9; p=0.01). 12 (40%) of 30 patients in the atorvastatin group improved by 1.3 units or more on the LCQ compared with five (17%) of 30 in the placebo group (difference 23%, 95% CI 1-45; p=0.04). Ten (33%) patients assigned atorvastatin had an adverse event versus three (10%) allocated placebo (difference 23%, 95% CI 3-43; p=0.02). No serious adverse events were recorded.
6 months of atorvastatin improved cough on a quality-of-life scale in patients with bronchiectasis. Multicentre studies are now needed to assess whether long-term statin treatment can reduce exacerbations.
The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation
1/05/13 → 30/10/19
1/04/11 → 31/03/17