Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma

Zeiger, Robert S.; Szefler, Stanley J.; Phillips, Brenda R.; Schätz, Michael; Martínez, Fernando D.; Chinchilli, Vernon M.; Lemanske, Robert F.; Strunk, Robert C.; Larsen, Gary L.; Spahn, Joseph D.; Bacharier, Leonard B.; Bloomberg, Gordon R.; Guilbert, Theresa W.; Heldt, Gregory P.; Morgan, Wayne J.; Moss, Mark H.; Sorkness, Christine A.; Taussig, Lynn M.

doi:10.1016/j.jaci.2005.10.012

Cited by 219 publications

(141 citation statements)

References 41 publications

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“…44 As expected, improvements in most clinical asthma control measures occurred with both FP and montelukast. However, clinical outcomes (asthma control days, the Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV 1 /forced vital capacity, PEF variabilities, morning PEF, and measures of impedance), and inflammatory biomarkers (eNO) improved significantly more with FP than with montelukast treatment.…”

Section: Characterizing the Response To A Leukotriene Receptor Antagosupporting

confidence: 67%

Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network

Denlinger¹,

Sorkness²,

Chinchilli

et al. 2007

Journal of Allergy and Clinical Immunology

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Due to an increasing prevalence, morbidity and mortality associated with asthma, the National Heart, Lung and Blood Institute created the Asthma Clinical Research Network (ACRN) and the Childhood Asthma Research and Education (CARE) Network to improve public health. The objectives of these clinical research networks are to conduct multiple, well designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the health care community. These trials comprise a large proportion of the data driving the treatment guidelines established and reviewed by the National Asthma Education and Prevention Program. This article will review the basic design and major findings of selected ACRN and CARE Network trials involving both adults and children with asthma. Collectively, these studies have helped refine the therapeutic role of existing controller medications, establish standard models for side effect evaluation and risk-benefit models, validate symptom based assessments for asthma control, and identify baseline characteristics that may predict individual patient responses. Remaining challenges include shaping the role of novel therapeutics in future guidelines, incorporating pharmacogenomic data in treatment decisions, and establishing better implementation strategies for translation to community settings, all with the goal of reducing the asthma burden on society.

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Section: Characterizing the Response To A Leukotriene Receptor Antagosupporting

confidence: 67%

Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network

Denlinger¹,

Sorkness²,

Chinchilli

et al. 2007

Journal of Allergy and Clinical Immunology

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“…Change in asthmacontrol days per week from baseline was measured in children with mild-to-moderate asthma participating in a cross-over NHLBI-CARE Network trial. Based on [5]. Figure 2.…”

Section: Ltra Icsmentioning

confidence: 99%

“…Clinical trials have shown a large range in BDR distribution upon SABA use. Although a large number of patients show a BDR >12%, approximately half of the patients have BDR values <12% and even a small subset of patients show a decrease in lung function upon SABA (negative BDR) [5]. Most patients show a response of 5-10%.…”

Section: Introductionmentioning

confidence: 99%

“…A large heterogeneity in treatment response is also observed for asthma maintenance treatment. A 16-week cross-over trial showed that children with mild-tomoderate asthma show a large distribution in improvement in asthma control days per week ( Figure 1) [5] or lung function improvement [6] upon treatment with ICS or LTRA. Change in asthma control days per week varied from an increase of seven asthma-controlled days per week to a decrease of four asthma-controlled days per week.…”

Section: Introductionmentioning

confidence: 99%

“…However, even in clinical trials in which adherence to treatment is closely monitored and patients groups are carefully selected, subsets of patients remain symptomatic despite maintenance treatment [5,6], suggesting that genetic variance plays a role as well. Heritability studies reported heritability estimates between 10% and 29% for SABA response [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Treatment response heterogeneity in asthma: the role of genetic variation

Vijverberg

Farzan

Slob

et al. 2017

Expert Review of Respiratory Medicine

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Introduction: Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short-and long-acting beta-2 agonists (SABA/ LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment. One of the most promising genetic variants is the Arg16 variant in the ADRB2 gene to guide LABA treatment in asthmatic children. Expert commentary: Poor replication of initially promising results and the low fraction of variability accounted for by single genetic variants inhibit pharmacogenetic findings to reach the asthma clinic. Nevertheless, the identification of genetic variation influencing treatment response does provide more insights in the complex processes underlying response and might identify novel targets for treatment. There is a need to report measures of clinical validity, to perform precision-medicine guided trials, as well as to understand how genetic variation interacts with environmental factors. In addition, systems biology approaches might be able to show a more complete picture of these complex interactions.ARTICLE HISTORY

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Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

Chauhan

Ducharme

2012

Cochrane Database of Systematic Reviews

187

107

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Background Anti-leukotrienes (5-lipoxygenase inhibitors and leukotriene receptors antagonists) serve as alternative monotherapy to inhaled corticosteroids (ICS) in the management of recurrent and/or chronic asthma in adults and children. Objectives To determine the safety and efficacy of anti-leukotrienes compared to inhaled corticosteroids as monotherapy in adults and children with asthma and to provide better insight into the influence of patient and treatment characteristics on the magnitude of effects. Search methods We searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (Dec 2010), abstract books, and reference lists of review articles and trials. We contacted colleagues and the international headquarters of anti-leukotrienes producers. Selection criteria We included randomised trials that compared anti-leukotrienes with inhaled corticosteroids as monotherapy for a minimum period of four weeks in patients with asthma aged two years and older. Data collection and analysis Two review authors independently assessed the methodological quality of trials and extracted data. The primary outcome was the number of patients with at least one exacerbation requiring systemic corticosteroids. Secondary outcomes included patients with at least one exacerbation requiring hospital admission, lung function tests, indices of chronic asthma control, adverse effects, withdrawal rates and biological inflammatory markers. Main results Sixty-five trials met the inclusion criteria for this review. Fifty-six trials (19 paediatric trials) contributed data (representing total of 10,005 adults and 3,333 children); 21 trials were of high methodological quality; 44 were published in full-text. All trials pertained to patients with mild or moderate persistent asthma. Trial durations varied from four to 52 weeks. The median dose of inhaled corticosteroids was quite homogeneous at 200 μg/day of microfine hydrofluoroalkane-propelled beclomethasone or equivalent (HFABDP eq). Patients treated with anti-leukotrienes were more likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077 participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For every 28 (95% CI 15 to 82) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional patient with an exacerbation requiring rescue systemic corticosteroids. The magnitude of effect was significantly greater in patients with moderate compared with those with mild airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97, 1.61), but was not significantly influenced by age group (children representing 23% of the weight versus adults), anti-leukotriene used, duration of intervention, methodological quality, and funding source. Significant group differences favouring inhaled corticosteroids were noted in most secondary outcomes including patients with at least one e...

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Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma

Cited by 219 publications

References 41 publications

Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network

Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network

Treatment response heterogeneity in asthma: the role of genetic variation

Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

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