FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1542912042> ?p ?o ?g. }

• W1542912042 abstract "BackgroundStatins are inhibitors of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, in cholesterol biosynthesis. As such, they have been widely used in clinical practice as cholesterol lowering agents to reduce morbidity and mortality from coronary artery disease. There is evidence from clinical studies and in vitro experiments that statins have additional anti-inflammatory properties in atherosclerotic disease, which are unrelated to their lipid lowering activity. Clinical studies have previously suggested that statins might show a beneficial clinical effect in inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Furthermore, preliminary data obtained in models of pulmonary inflammation suggest that the effects manifest in rheumatoid patients can be achieved also in asthma. A proof of concept study was designed to test the hypothesis that atorvastatin improves asthma control and airway inflammation in adults with asthma. MethodsFifty four adults with allergic asthma were recruited to a 22-week crossover randomised controlled trial comparing the effect on asthma control and airway inflammation of oral atorvastatin 40 mg daily with that of a matched placebo. Each treatment was administered for 8 weeks separated by a 6-week washout period. The primary outcome was morning peak expiratory flow. Secondary outcomes included spirometry, asthma control questionnaire (ACQ) score, asthma quality of life questionnaire (AQLQ), provocation concentration to methacholine (PC20) and inflammatory markers: exhaled nitric oxide, sputum differential cell count, sputum supernatant and serum inflammatory markers such as interleukin-6 (IL-6), IL-5, IL-8, sICAM-1, TNF-α, leukotriene B4 (LTB4) and high sensitivity C-reactive protein (hsCRP), and blood lymphocyte proliferation. ResultsAt 8 weeks, the change in mean morning PEF, as compared with baseline, did not differ between the atorvastatin and placebo treatment periods [mean difference -0.5 L/min, 95% CI -10.6 to 9.6, p=0.921]. No statistically significant effect of atorvastatin was seen in evening PEF, or methacholine responsiveness (PC20). Out of all spirometry results, only post-salbutamol FVC showed a statistically significant result, which was slightly lower in the atorvastatin group [treatment difference -0.1L, 95% CI -0.2 to 0.0, p=0.037]. There was also no change in ACQ or AQLQ. No change was seen in exhaled nitric oxide. The total cell counts recovered from sputum were similar after atorvastatin compared to after placebo treatment. After 8 weeks, the mean absolute and relative sputum macrophage count was significantly reduced after atorvastatin compared to placebo [mean absolute difference -44.9x104 cells, 95% CI -80.1 to -9.7, p=0.029]. There was a reciprocal increase in the relative proportion of sputum neutrophils [mean proportion difference 13.1%, 95% CI 1.8 to 24.4, p=0.025], but there were no significant changes in the absolute count of these cells or the counts and proportions of the other sputum cell phenotypes under atorvastatin treatment.The sputum concentrations of inflammatory cytokines and mediators were similar after atorvastatin compared to after placebo treatment other than LTB4 which was significantly reduced [mean difference -88.1 pg/mL, 95% CI -156.4 to -19.9, p=0.014].No significant difference was seen in the concentration of any serum marker of inflammation between atorvastatin and placebo treatment periods. The change in hsCRP was of borderline significance [mean difference -0.65 mg/L, 95% CI -1.38 to 0.09, p=0.082], but there were no changes in sICAM-1, TNF-α, IL-5, IL-6 and IL-8. There was no significant difference in lymphocyte proliferation. The biochemical effects of atorvastatin therapy were reflected in significant reduction in concentration of serum lipids; cholesterol (mean difference -1.71 mmol/l, 95% CI -1.94 to -1.48 p<0.0001), and HDL-cholesterol (mean difference -0.14 mmol/l, 95% CI -0.26 to -0.02 p=0.026), but not triglycerides. There were significant, albeit modest, increases in mean bilirubin, AST and ALT. There was no difference in compliance, assessed by number of tablets returned and by biochemical results.There was no correlation between changes in LTB4 or IL-8 and sputum macrophage count, sputum neutrophil count, or PEF. The only correlation observed between the variables that were compared was between sputum macrophages and neutrophils.Adverse event rates were similar in patients taking atorvastatin compared with placebo. Equal numbers of patients were lost to follow-up in both arms of the study. One patient died of unrelated causes while taking the placebo medication.Conclusions There were no clinically important improvements in a range of clinical indices of asthma control after eight weeks of treatment with atorvastatin despite expected changes in serum lipids. There were however changes in airway inflammation and in particular, a reduction in the absolute sputum macrophage count after atorvastatin compared to placebo and an associated reduction in sputum LTB4 and a trend towards lower CRP.The lack of any evidence of clinical benefit of atorvastatin in allergic asthma confirms and extends the findings of a smaller randomised placebo controlled crossover trial of simvastatin in 16 subjects with asthma, which showed no change in clinical outcomes or inflammatory markers. It is unlikely that altering duration of treatment, washout period or type of statin used would have changed the outcome of the study. However, as all patients were receiving inhaled corticosteroid as part of their asthma therapy, it is possible that this may have masked any modest anti-inflammatory effects of the statin. Baseline asthma inflammation may also have been too low to show any significant improvement.Despite the postulated anti-inflammatory actions of statins, it seems that they may not be appropriate for the inflammatory phenotype associated with atopic asthma. The reduction in alveolar macrophage count found in patients with allergic asthma may however have relevance to the treatment of chronic lung diseases such as COPD in which alveolar macrophage function has been implicated in the pathogenesis." @default.
• W1542912042 created "2016-06-24" @default.
• W1542912042 creator A5055550273 @default.
• W1542912042 date "2008-12-05" @default.
• W1542912042 modified "2023-09-27" @default.
• W1542912042 title "Effect of atorvastatin on asthma control and airway inflammation : a randomised controlled trial" @default.
• W1542912042 hasPublicationYear "2008" @default.
• W1542912042 type Work @default.
• W1542912042 sameAs 1542912042 @default.
• W1542912042 citedByCount "1" @default.
• W1542912042 countsByYear W15429120422012 @default.
• W1542912042 crossrefType "dissertation" @default.
• W1542912042 hasAuthorship W1542912042A5055550273 @default.
• W1542912042 hasConcept C126322002 @default.
• W1542912042 hasConcept C142724271 @default.
• W1542912042 hasConcept C168563851 @default.
• W1542912042 hasConcept C203014093 @default.
• W1542912042 hasConcept C2776042228 @default.
• W1542912042 hasConcept C2776301714 @default.
• W1542912042 hasConcept C2777482532 @default.
• W1542912042 hasConcept C2777575956 @default.
• W1542912042 hasConcept C2780333948 @default.
• W1542912042 hasConcept C2781069245 @default.
• W1542912042 hasConcept C2781142857 @default.
• W1542912042 hasConcept C71924100 @default.
• W1542912042 hasConceptScore W1542912042C126322002 @default.
• W1542912042 hasConceptScore W1542912042C142724271 @default.
• W1542912042 hasConceptScore W1542912042C168563851 @default.
• W1542912042 hasConceptScore W1542912042C203014093 @default.
• W1542912042 hasConceptScore W1542912042C2776042228 @default.
• W1542912042 hasConceptScore W1542912042C2776301714 @default.
• W1542912042 hasConceptScore W1542912042C2777482532 @default.
• W1542912042 hasConceptScore W1542912042C2777575956 @default.
• W1542912042 hasConceptScore W1542912042C2780333948 @default.
• W1542912042 hasConceptScore W1542912042C2781069245 @default.
• W1542912042 hasConceptScore W1542912042C2781142857 @default.
• W1542912042 hasConceptScore W1542912042C71924100 @default.
• W1542912042 hasLocation W15429120421 @default.
• W1542912042 hasOpenAccess W1542912042 @default.
• W1542912042 hasPrimaryLocation W15429120421 @default.
• W1542912042 hasRelatedWork W1750369209 @default.
• W1542912042 hasRelatedWork W1809380315 @default.
• W1542912042 hasRelatedWork W1891992088 @default.
• W1542912042 hasRelatedWork W1922210558 @default.
• W1542912042 hasRelatedWork W1992347215 @default.
• W1542912042 hasRelatedWork W2047124405 @default.
• W1542912042 hasRelatedWork W2056247034 @default.
• W1542912042 hasRelatedWork W2140688081 @default.
• W1542912042 hasRelatedWork W2384391157 @default.
• W1542912042 hasRelatedWork W2517353134 @default.
• W1542912042 hasRelatedWork W2589847333 @default.
• W1542912042 hasRelatedWork W2769186313 @default.
• W1542912042 hasRelatedWork W2775898690 @default.
• W1542912042 hasRelatedWork W2781454027 @default.
• W1542912042 hasRelatedWork W2990215157 @default.
• W1542912042 hasRelatedWork W3009646908 @default.
• W1542912042 hasRelatedWork W3029041811 @default.
• W1542912042 hasRelatedWork W3030741266 @default.
• W1542912042 hasRelatedWork W3031181435 @default.
• W1542912042 hasRelatedWork W3032499036 @default.
• W1542912042 isParatext "false" @default.
• W1542912042 isRetracted "false" @default.
• W1542912042 magId "1542912042" @default.
• W1542912042 workType "dissertation" @default.