scholarly journals Tailored second-line therapy in asthmatic children with the Arg16 genotype

2013 ◽  
Vol 124 (8) ◽  
pp. 521-528 ◽  
Author(s):  
Brian J. Lipworth ◽  
Kaninika Basu ◽  
Helen P. Donald ◽  
Roger Tavendale ◽  
Donald F. Macgregor ◽  
...  
Keyword(s):  
Forced Expiratory Volume ◽  
Second Line ◽  
Once Daily ◽  
Asthmatic Children ◽  
Long Acting ◽  
To Receive ◽  
Β2 Agonists ◽  
Genotype A ◽  
Increased Susceptibility

The Arg16 β2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting β2 agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 μg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score=−0.40 [95% CI (confidence interval), −0.22 to −0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score=−0.47 (95% CI, −0.16 to −0.79); P<0.0001]. Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol, whereas there was no difference in FEV1 (forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg16 genotype, a move towards a personalized medicine approach to management.

β 2-Adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting β2-agonist therapy

1999 ◽  
Vol 96 (3) ◽  
pp. 253-259 ◽  
Author(s):  
B. J. LIPWORTH ◽  
I. P. HALL ◽  
I. AZIZ ◽  
K. S. TAN ◽  
A. WHEATLEY
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Double Blind ◽  
Geometric Means ◽  
Once Daily ◽  
Regular Treatment ◽  
Parallel Group ◽  
Long Acting ◽  
To Receive ◽  
Β2 Agonist

The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting β2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12μg once daily, 6μg twice daily or 24μg twice daily) or terbutaline (500μg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 ;s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without β2-agonist, and at 1 ;h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and β2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as μg of methacholine, geometric means±S.E.M.): formoterol, 12μg once daily, 99±42μg; formoterol, 6μg twice daily, 107±44μg; formoterol, 24μg twice daily, 108±45μg; terbutaline, 500μg four times daily, 88±37μg. All patients receiving formoterol, 24μg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12μg once daily or 6μg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean±S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66±11%; Het-16, 53±8%; Arg-16, 69±18%; Glu-27, 68±12%; Het-27, 58±8%; Gln-27, 52±12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting β2-agonist exposure irrespective of β2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.

scholarly journals Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
David Miller ◽  
Soniya Vaidya ◽  
Juergen Jauernig ◽  
Brian Ethell ◽  
Kristina Wagner ◽  
...  
Keyword(s):  
Lung Function ◽  
Systemic Exposure ◽  
Forced Expiratory Volume ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Electronic Diary ◽  
Double Blind ◽  
Once Daily ◽  
Long Acting ◽  
Salt Forms

Abstract Background Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β2-agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, inhaled fixed dose combination (FDC) of indacaterol, glycopyrronium bromide (a long-acting muscarinic antagonist), and mometasone furoate (an inhaled corticosteroid [ICS]) for the treatment of patients with asthma, the acetate salt of indacaterol is used instead of the maleate salt. Here, we investigated the lung function, pharmacokinetics (PK) and safety of indacaterol maleate 150 μg once daily (o.d.) and indacaterol acetate 150 μg o.d. in comparison with placebo. Methods This was a randomised, double-blind, three-period crossover study (ClinicalTrials.gov identifier, NCT03257995) in patients with asthma on background ICS therapy. Patients with percent predicted pre-bronchodilator forced expiratory volume per second (FEV1) ≥50% and ≤ 90% were included in the study. Patients received indacaterol maleate 150 μg o.d., indacaterol acetate 150 μg o.d., or placebo on top of stable background ICS in randomised sequence. Trough FEV1 was assessed after 14 days of treatment. PK of indacaterol salts were assessed at steady state after 14 days of treatment; peak expiratory flow (PEF) rate and rescue medication use were collected with a combined PEF-meter/electronic diary throughout the study. Results Of the 54 adult patients (median age of 48 years), 51 patients completed the study. Both indacaterol salts demonstrated statistically significant improvements in trough FEV1 of 186 mL (maleate) and 146 mL (acetate) compared with placebo (both P < 0.001). FEV1 AUC0-4h improved by 248 mL (maleate) and 245 mL (acetate), and PEF by 33 L/min (maleate) and 30.8 L/min (acetate) versus placebo. Systemic exposure of indacaterol (AUC0-24h,ss and Cmax,ss on Day 14) was comparable after administration of both salt forms. Both salt forms demonstrated a good safety profile and were well tolerated, with a difference in the reporting frequency of AEs of coughing (maleate, 23.5%; acetate, 0%). Conclusions In patients with asthma, indacaterol maleate and acetate elicited comparable and significant improvements in lung function compared with placebo and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated. Trial registration ClinicalTrials.gov NCT03257995 June 06, 2017

scholarly journals Combination of ICSs and LABAs Should Be Used in the Management of Patients with COPD — The Con Argument

2004 ◽  
Vol 11 (3) ◽  
pp. 224-226
Author(s):  
Jeremy Road
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Randomized Controlled ◽  
The Past ◽  
Related Quality ◽  
Health Related ◽  
Long Acting

The management of patients with symptomatic chronic obstructive pulmonary disease (COPD) has become more clear in the past several years. New medications have been developed and their efficacy has been evaluated using important outcomes in addition to forced expiratory volume in 1 s (FEV1), such as health-related quality of life (HRQL), frequency of exacerbations and dyspnea scores. I will review five welldesigned, randomized, controlled trials that have advanced our knowledge about the use of inhaled corticosteroids (ICSs), long-acting beta2-agonists (LABAs) and their combination.

Randomized Phase III Trial Exploring the Use of Long-Acting Release Octreotide in the Prevention of Chemotherapy-Induced Diarrhea in Patients With Colorectal Cancer: The LARCID Trial

2014 ◽  
Vol 32 (10) ◽  
pp. 1006-1011 ◽  
Author(s):  
Paulo M. Hoff ◽  
Daniel F. Saragiotto ◽  
Carlos H. Barrios ◽  
Auro del Giglio ◽  
Anelisa K. Coutinho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Common Adverse Event ◽  
Phase Iii ◽  
Control Group ◽  
Phase Iii Trial ◽  
Octreotide Lar ◽  
Intravenous Hydration ◽  
Long Acting ◽  
To Receive

PurposeChemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of patients with colorectal cancer. The LAR for Chemotherapy-Induced Diarrhea (LARCID) trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population.Patients and MethodsPatients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil, capecitabine, and/or irinotecan were randomly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks (experimental arm) or the physician's treatment of choice in case of diarrhea (control arm).ResultsA total of 139 patients were randomly assigned, most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of patients. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration or in the rate of hospitalization or quality of life.ConclusionThis study could not prove the efficacy of octreotide LAR in the prevention of CID.

Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: A double-blind study

1991 ◽  
Vol 125 (4) ◽  
pp. 385-391 ◽  
Author(s):  
J. A. Verhelst ◽  
A. L. Froud ◽  
R. Touzel ◽  
J. A. H. Wass ◽  
G. M. Besser ◽  
...  
Keyword(s):  
Dopamine Agonist ◽  
Adverse Reactions ◽  
Double Blind Study ◽  
Long Term Effects ◽  
Double Blind ◽  
Once Daily ◽  
Long Acting ◽  
To Receive ◽  
Blind Manner

Abstract. Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

Comparison of a Long-Acting Form of Propranolol and Conventional Propranolol in the Treatment of Hypertension in Elderly Patients

1987 ◽  
Vol 15 (3) ◽  
pp. 128-133
Author(s):  
A. U. Khan
Keyword(s):  
Elderly Patients ◽  
Second Line ◽  
Double Blind ◽  
Once Daily ◽  
Hypertensive Patients ◽  
Treatment Of Hypertension ◽  
Blood Pressures ◽  
Elderly Hypertensive ◽  
Elderly Hypertensive Patients ◽  
Long Acting

Nineteen elderly hypertensive patients already being treated with a diuretic and, where necessary, another anti-hypertensive agent, were studied in a double-blind, randomized, crossover comparison of conventional propranolol, 40 mg three times daily, with a long-acting propranolol formulation, 160 mg once daily, as a second line agent. Patients were assessed before taking the morning's allocated medication. This was done as near as possible to 24 h after the last dose of once daily propranolol and as near as possible to 15 h after the last dose of three times daily conventional propranolol. Assessment was carried out at the time of randomization and after 4 weeks' treatment with both propranolol formulations. Heart rate and blood pressures were measured in the supine and standing positions and after exercise. Both propranolol formulations were effective as second line agents in these elderly patients and both were well tolerated. Patient compliance on both propranolol formulations was very good although the long-acting formulation may be of value in improving this still further.

scholarly journals Allergic Rhinitis Improvement in Asthmatic Children After Using Acaricidal Bait: A Randomized, Double-Blind, Cross-Placebo Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Ming Chen ◽  
Yufen Wu ◽  
Shuhua Yuan ◽  
Mingyu Tang ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Life Questionnaire ◽  
Double Blind ◽  
Asthma Control Questionnaire ◽  
Asthmatic Children ◽  
Dust Mite ◽  
Allergen Concentration ◽  
Placebo Intervention ◽  
To Receive

Objective: This study aimed to evaluate the effects of acaricidal bait use on the house dust mite (HDM) allergen concentration and occurrence of allergic rhinitis (AR) and asthma symptoms in children sensitized to HDMs.Study Design: Sixty-six children (3–12 years old) with AR and asthma sensitized to HDMs were randomly assigned to receive an acaricidal bait intervention for 8 weeks and a placebo intervention for 8 weeks separated by a 4-week washout period. The visual analog scale (VAS) score, rhinitis control assessment test (RCAT) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score, asthma control questionnaire-5 (ACQ-5) score and HDM allergen levels were monitored.Results: HDM allergen levels were significantly decreased after 8 weeks (Δder p2+f2 2.282 (3.516) μg/g vs. 0.147 (0.25) μg/g, P &lt; 0.05) in the acaricidal bait group compared with the placebo group. The VAS, RCAT and RQLQ scores in the acaricidal bait group were also significantly improved (ΔVAS 7.5 (16) vs. 3 (18), P &lt; 0.05; ΔRCAT−3 (5) vs. 0 (7), P &lt; 0.05; ΔRQLQ 4.5 (8) vs. 1 (8), P &lt; 0.05), but the ACQ-5 score did not improve (ΔACQ-5 0.2 (0.4) vs. 0 (0.65), P &gt; 0.05).Conclusion: Acaricidal bait reduced HDM exposure and improved rhinitis symptoms. This trial is registered at www.chictr.org.cn.

scholarly journals Comparison of Prospective and Retrospective Indicators of the Quality of End-of-Life Cancer Care

2008 ◽  
Vol 26 (35) ◽  
pp. 5671-5678 ◽  
Author(s):  
Soko Setoguchi ◽  
Craig C. Earle ◽  
Robert Glynn ◽  
Margaret Stedman ◽  
Jennifer M. Polinski ◽  
...  
Keyword(s):  
End Of Life ◽  
End Of Life Care ◽  
Acute Care Hospital ◽  
Teaching Hospitals ◽  
Care Hospital ◽  
Life Care ◽  
Cancer Registry Data ◽  
Long Acting ◽  
To Receive

Purpose To compare prospectively and retrospectively defined benchmarks for the quality of end-of-life care, including a novel indicator for the use of opiate analgesia. Methods Linked claims and cancer registry data from 1994 to 2003 for New Jersey and Pennsylvania were used to examine prospective and retrospective benchmarks for seniors with breast, colorectal, lung, or prostate cancer who participated in state pharmaceutical benefit programs. Results Use of opiates, particularly long-acting opiates, was low in both the prospective and retrospective cohorts (9.1% and 10.1%, respectively), which supported the underuse of palliative care at the end-of-life. Although hospice was used more commonly in the retrospective versus prospective cohort, admission to hospice within 3 days of death was similar in both cohorts (28.8% v 26.4%), as was the rate of death in an acute care hospital. Retrospective and prospective measures identified similar physician and hospital patterns of end-of-life care. In multivariate models, a visit with an oncologist was positively associated with the use of chemotherapy, opiates, and hospice. Patients who were cared for by oncologists in small group practices were more likely to receive chemotherapy (retrospective only) and less likely to receive hospice (both) than those in large groups. Compared with patients who were cared for in teaching hospitals, those in other hospitals were more likely to receive chemotherapy (both) and to have toxicity (prospective) but were less likely to receive opiates (both) and hospice (retrospective). Conclusion Retrospective and prospective measures, including a new measure of the use of opiate analgesia, identify some similar physician and hospital patterns of end-of-life care.

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