Faculty Opinions recommendation of Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents.

Author(s):  
Gerard H Koppelman
Keyword(s):  
Beta 2 ◽  
Thorax ◽  
1999 ◽  
Vol 54 (6) ◽  
pp. 482-487 ◽  
Author(s):  
R J Hancox ◽  
J O Cowan ◽  
E M Flannery ◽  
G P Herbison ◽  
C R McLachlan ◽  
...  

2021 ◽  
pp. 2004107
Author(s):  
Tom Ruffles ◽  
Christina J Jones ◽  
Colin Palmer ◽  
Steve Turner ◽  
Jonathan Grigg ◽  
...  

IntroductionThe A allele of rs1042713 (Arg16 amino acid) in the beta-2 (β2) adrenoreceptor is associated with poor response to long-acting β2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second line controller with LABA or a leukotriene receptor antagonist (LTRA) according to Arg16Gly genotype would result in improvements in pediatric asthma-related quality of life questionnaire (PAQLQ).MethodsWe performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12–18 years with asthma taking inhaled corticosteroids. A total of 241 participants (mean (sd) age 14.7 years (1.91)) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following 4-week run-in participants were followed for 12-months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes.ResultsGenotype directed prescribing resulted in an improvement in PAQLQ compared to standard care 0.16, (95%CI 0.00–0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care 0.42, (95%CI 0.02–0.81; p=0.041).ConclusionThis is the first RCT demonstrating that genotype driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such β2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Teele Kasepalu ◽  
Karl Kuusik ◽  
Urmas Lepner ◽  
Joel Starkopf ◽  
Mihkel Zilmer ◽  
...  

Background and Aims. Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. Results. Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p=0.021, p=0.021, p=0.024, and p=0.015, respectively). Comparison of two time points, baseline and 24 hours after surgery, revealed that the change in creatinine, eGFR, urea, cystatin C, and beta-2 microglobulin was significantly different between the groups (p<0.05). Conclusions. Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.


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