Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review

Kankaanranta, Hannu; Lahdensuo, A; Moilanen, Eeva; Barnes, Peter J.

doi:10.1186/1465-9921-5-17

Cited by 57 publications

(48 citation statements)

References 119 publications

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“…Combination therapy with LABA and inhaled corticosteroids reduces the frequency of exacerbations in asthma, and it is also efficacious as an interventional therapy in asthma exacerbations (16)(17)(18). In this study, SAL was able to suppress the production of TSLP in NHBE cells, and we also demonstrated the synergistic suppression of poly(I:C)-induced TSLP production by DEX and SAL in NHBE cells.…”

Section: Discussionsupporting

confidence: 56%

“…A suppressive effect of glucocorticoid on the expression of TSLP induced in airway epithelial cells by stimulation with the TLR3 ligand and Th2 cytokines was reported (14). In addition, several clinical studies showed that the combination of an inhaled corticosteroid and long-acting b-adrenergic agonist (LABA) is more efficacious in asthma than either alone, and reduces exacerbations (15)(16)(17)(18). We investigated the effects of dexamethasone (DEX) and salmeterol (SAL) on the induction of TSLP by poly(I:C).…”

Section: Clinical Relevancementioning

confidence: 99%

See 1 more Smart Citation

Thymic Stromal Lymphopoietin Gene Promoter Polymorphisms Are Associated with Susceptibility to Bronchial Asthma

Harada

Hirota

Jodo

et al. 2011

Am J Respir Cell Mol Biol

198

171

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Thymic stromal lymphopoietin (TSLP) triggers dendritic cell-mediated T helper (Th) 2 inflammatory responses. A single-nucleotide polymorphism (SNP), rs3806933, in the promoter region of the TSLP gene creates a binding site for the transcription factor activating protein (AP)-1. The variant enhances AP-1 binding to the regulatory element, and increases the promoter-reporter activity of TSLP in response to polyinosinic-polycytidylic acid (poly[I:C]) stimulation in normal human bronchial epithelium (NHBE). We investigated whether polymorphisms including the SNP rs3806933 could affect the susceptibility to and clinical phenotypes of bronchial asthma. We selected three representative (i.e., Tag) SNPs and conducted association studies of the TSLP gene, using two independent populations (639 patients with childhood atopic asthma and 838 control subjects, and 641 patients with adult asthma and 376 control subjects, respectively). We further examined the effects of corticosteroids and a long-acting b 2 -agonist (salmeterol) on the expression levels of the TSLP gene in response to poly(I:C) in NHBE. We found that the promoter polymorphisms rs3806933 and rs2289276 were significantly associated with disease susceptibility in both childhood atopic and adult asthma. The functional SNP rs3806933 was associated with asthma (meta-analysis, P 5 0.000056; odds ratio, 1.29; 95% confidence interval, 1.14-1.47). A genotype of rs2289278 was correlated with pulmonary function. Moreover, the induction of TSLP mRNA and protein expression induced by poly(I:C) in NHBE was synergistically impaired by a corticosteroid and salmeterol. TSLP variants are significantly associated with bronchial asthma and pulmonary function. Thus, TSLP may serve as a therapeutic target molecule for combination therapy.Keywords: asthma; TSLP; bronchial epithelial cells; combination therapy; genetic polymorphisms Thymic stromal lymphoprotein (TSLP) is an epithelial cellderived cytokine that triggers dendritic cell-mediated T helper (Th) 2 inflammatory responses, and plays an important role in the initiation and maintenance of the allergic immune response (1-6). A recent study showed that TSLP is released by human epithelial cells in response to microbes, trauma, or inflammation, and potently activates mast cells (7). In humans, TSLP is highly expressed by airway epithelial cells during allergic inflammation (2), and the expression of the TSLP gene in asthmatic airways is correlated with both the expression of Th2-attracting chemokines and disease severity (3).Large numbers of association studies on asthma and asthmarelated phenotypes using genetic polymorphisms were performed in different populations (8). Recent studies showed roles of human genetic polymorphisms of the TSLP gene. A variant in TSLP was associated with reductions in IgE in response to cockroaches and total IgE in a sex-stratified analysis (9). A functional single-nucleotide polymorphism (SNP), rs3806933, was identified in the regulatory element of TSLP (10). The variant creates a binding site for a...

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Section: Discussionsupporting

confidence: 56%

Section: Clinical Relevancementioning

confidence: 99%

Thymic Stromal Lymphopoietin Gene Promoter Polymorphisms Are Associated with Susceptibility to Bronchial Asthma

Harada

Hirota

Jodo

et al. 2011

Am J Respir Cell Mol Biol

198

171

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“…250 Kankaanranta and colleagues 250 aimed to review systematically the evidence that supports different treatment options for asthma, including increasing the dose of ICS, and the use of add-on therapy options such as a LABA, leukotriene antagonist or theophylline. Jarvis and Faulds 249 evaluated the therapeutic efficacy of FP at doses ഛ500 µg/day, and included comparisons with placebo, nonsteroidal, anti-inflammatory agents, other ICS drugs (BDP, BUD, flunisolide and triamcinolone acetonide), and combination with SAL.…”

Section: Other Systematic Reviewsmentioning

confidence: 99%

“…The number of participants was not reported in either review. Participants included in the reviews were adults or adolescents (one review 250 defined adolescents as aged >12 years) with mild to moderate asthma 249 or asthma that was inadequately controlled with ICS 250 (results are reported for patients with mild and moderate to severe asthma).…”

Section: Kankaanranta and Colleaguesmentioning

confidence: 99%

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Shepherd¹,

Rogers²,

Anderson³

et al. 2008

Health Technol Assess

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Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30-40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email. Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA Programme and lists the membership of the various committees. HTA NIHR Health Technology Assessment ProgrammeT he Health Technology Assessment (HTA) Programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. The research findings from the HTA Programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'. The HTA Programme is needs-led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects. First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, the public and consumer groups and professional bodies such as royal colleges and NHS trusts. These sugges...

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“…nhaled corticosteroids are the mainstay of asthma therapy, but there is now compelling evidence that addition of a long-acting inhaled b 2 -agonist (LABA; salmeterol or formoterol) gives better control in terms of reduced symptoms, improved lung function and reduced exacerbations in patients with mild, moderate and severe persistent asthma than increasing the dose of corticosteroids in patients not fully controlled on low doses [1][2][3][4][5]. This has led to the development of fixed combination inhalers, fluticasone/salmeterol (Seretide2/Advair2, GlaxoSmithKline), and budesonide/formoterol (Symbicort1, AstraZeneca), which are now increasingly used in asthma management [6,7].…”

mentioning

confidence: 99%

Scientific rationale for using a single inhaler for asthma control

Barnes¹

2007

Eur Respir J

139

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Clinical trials have recently demonstrated that using a budesonide/formoterol combination inhaler as regular maintenance treatment twice daily but also as a rescue therapy for breakthrough symptoms can provide more effective control of asthma, particularly in reducing exacerbations, than using a short-acting b 2 -agonist or formoterol as rescue therapy. This suggests that the corticosteroid component of the combination therapy plays an important role in rescue therapy.Formoterol as a rescue therapy is effective in relieving symptoms by relaxing airway smooth muscle but is also likely to have important inhibitory effects on mast cells, plasma exudation and neutrophilic inflammation.Inhaled corticosteroids have much more rapid suppressing effects on airway inflammation than previously recognised and the increased dose used as rescue therapy may prevent the increase in airway inflammation that occurs during the evolution of an exacerbation, thus preventing its development.It is likely that the molecular interactions between b 2 -agonists and corticosteroids also enhance the effect of the combination therapy as rescue therapy. There is now a strong scientific rationale for single inhaler therapy in asthma, but more research is now needed to better understand the mechanisms involved.

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Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review

Cited by 57 publications

References 119 publications

Thymic Stromal Lymphopoietin Gene Promoter Polymorphisms Are Associated with Susceptibility to Bronchial Asthma

Thymic Stromal Lymphopoietin Gene Promoter Polymorphisms Are Associated with Susceptibility to Bronchial Asthma

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Scientific rationale for using a single inhaler for asthma control

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