Inhalation of Corticosteroids in Smoking and Non-smoking Asthmatics.
NCT ID: NCT01400906
Last Updated: 2018-08-13
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
36 participants
Study Classification
INTERVENTIONAL
Study Start Date
2011-07-20
Study Completion Date
2012-12-12
Brief Summary
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People with asthma suffer from breathlessness because the small tubes (bronchioles) that carry air in and out of the lungs become inflamed and narrow. Steroids reduce the inflammation, and are commonly used to control asthma, but they do not work well in some asthmatics, particularly those who smoke.
This study is done to find out more about why smokers with asthma do not benefit from steroid treatment. In this study, the effect of Flixotide (fluticasone propionate), a steroid widely used to treat asthma, is tested in smokers and non-smokers with mild asthma.
16 smokers and 16 non-smokers, aged 18-55 years will be enrolled in this study.
Subjects will take each of the following treatments:
* 100 micrograms Flixotide twice daily for 7 days;
* 500 micrograms Flixotide twice daily for 7 days; and
* placebo (dummy medicine) twice daily for 7 days.
Study design: subjects will have a screening visit (over 2 days), and will take part in 3 treatment periods (which are separated by interval of at least 14 days); a follow-up visit is scheduled 7 days after the last intake of study treatment.
The order in which order the subjects will take the treatments is defined at random. Total study duration: about 11 weeks.
To test the effects of Flixotide, the subject's responses to :
* an inhaled allergen test
* a PC20 methacholine test
* blood, urine and sputum PD markers will be analysed.
This study will take place in 2 centres: 1 in the United Kingdom and 1 in Belgium. The units will recruit participants by advertising (newspaper, radio, and websites), word of mouth, from volunteer databases, and via the centres' websites.
This study is done to find out more about why smokers with asthma do not benefit from steroid treatment. In this study, the effect of Flixotide (fluticasone propionate), a steroid widely used to treat asthma, is tested in smokers and non-smokers with mild asthma.
16 smokers and 16 non-smokers, aged 18-55 years will be enrolled in this study.
Subjects will take each of the following treatments:
* 100 micrograms Flixotide twice daily for 7 days;
* 500 micrograms Flixotide twice daily for 7 days; and
* placebo (dummy medicine) twice daily for 7 days.
Study design: subjects will have a screening visit (over 2 days), and will take part in 3 treatment periods (which are separated by interval of at least 14 days); a follow-up visit is scheduled 7 days after the last intake of study treatment.
The order in which order the subjects will take the treatments is defined at random. Total study duration: about 11 weeks.
To test the effects of Flixotide, the subject's responses to :
* an inhaled allergen test
* a PC20 methacholine test
* blood, urine and sputum PD markers will be analysed.
This study will take place in 2 centres: 1 in the United Kingdom and 1 in Belgium. The units will recruit participants by advertising (newspaper, radio, and websites), word of mouth, from volunteer databases, and via the centres' websites.
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Detailed Description
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Most patients with asthma are successfully treated with inhaled corticosteroid (ICS) therapy, either alone or in combination with long-acting beta 2-agonists, with minimal or no side effects. However, a significant proportion of asthmatic patients, including present cigarette smokers and former cigarette smokers, fail to respond well to ICS, alone or in combination with other therapies.
In a randomized, placebo-controlled study, the efficacy of inhaled fluticasone propionate (FP), 1000 μg/day on peak expiratory flow (PEF) and bronchial hyper-reactivity in smokers with mild asthma was assessed compared with non-smoking asthmatics. Asthmatics who smoked showed impaired responses to ICS therapy compared with non-smoking asthmatics \[Chalmers, 2002\] and this lack of responsiveness appears to be dose-dependent. When the dose of ICS is increased, the disparity between lung function, rescue inhaler usage and asthma control seen in smokers and non-smokers decreases \[Tomlinson, 2005\].
Interestingly, smoking also affects the ability of ICS to suppress exhaled nitric oxide (eNO) levels in asthmatics \[Horváth, 2004\]. Smoking cessation improves basal lung function but requires at least a year to demonstrate any improvement in Glucocorticoid (GC) responsiveness with respect to morning peak expiratory flow, but not FEV1, after therapy with high-dose oral prednisolone \[Chaudhuri , 2006\].
Smoking asthmatics have more severe disease requiring more therapy, have more hospital admissions and are more likely to die from asthma \[Thomson, 2005\].
Cigarette smoking remains therefore one of the commonest causes of steroid resistance in asthma, however many aspects of the development and restoration of corticosteroid resistance remain unclarified in this population partly due to the paucity of studies performed.
The mechanisms underlying GC resistance in smoking asthmatics are incompletely understood but are thought to include noneosinophilic (often neutrophilic) airway inflammation \[Chalmers, 2001\], impaired corticosteroid receptor function, and/or reduced histone deacetylase activity \[Adcock, 2008\]. In support of these effects of smoking on asthma, animal models show that smoking can increase inflammation in allergic models of asthma and can affect steroid responsiveness.
Tobacco smoke exposure (4 cigarettes/day for 3weeks) had a small neutrophilic effect in mice, whereas ovalbumin exposure had no inflammatory effect in the airways, but increased allergen-specific IgE \[Moerloose, 2006\]. More recently in mouse models, cigarette smoke has been shown to enhance T-helper-(TH)2-driven airway inflammation \[Van Hove , 2008\].
Inhaled allergens are an important trigger of exacerbations in asthma \[Johnston, 2006\].
The airway inflammation induced by inhaled allergens, and the effects of drugs on this airway inflammation, can be studied using an experimental allergen challenge model. All the currently approved drugs used to treat asthma modify, in some way, allergen-induced airway responses. Following inhalation of the appropriate allergen extract, sensitive subjects, i.e. atopic-asthmatics, develop an acute bronchoconstriction which peaks at 20 to 30 minutes post-allergen and lasts for approximately two hours before recovery.
This early response (EAR) reflects mast cell activation and subsequent release of mainly spasmogenic mediators and correlates with the extent of airway inflammation and disease activity \[Grzelewska-Rsymowska, 1995\]. In approximately 50% of patients, the EAR is followed by a late-phase asthmatic response (LAR). This more prolonged airway narrowing is associated with influx of activated inflammatory cells, especially eosinophils, into the airways and represents the more chronic features of asthma, consisting of a prolonged airway narrowing through both bronchospasm and airway inflammation.
The sequelae of the LAR can last several days and up to 3 weeks. Also, the late response has been shown to be associated with an increase in airway hyperresponsiveness (AHR) to stimuli, such as methacholine for several days after allergen challenge \[Hansel, 2002\].
This clinically relevant model of allergic bronchoconstriction has been useful in humans for exploring the time-course of cellular inflammation and the associated physiological changes, particularly related to eosinophils, basophils and dendritic cells \[O'Byrne, 2009\].In non smoking asthmatics, regular treatment with inhaled corticosteroids has been shown to attenuate the early allergic response, perhaps by reducing the number of mast cells in airways \[Gauvreau, 2000\] and to improve the late-phase asthmatic response \[Kidney, 1997; Cockcroft, 1987\].
As previous allergen challenge studies with therapeutic interventions have been conducted only in the population of non-smokers, this study will be the first to examine the allergen challenge response to FP in smoking asthmatics. The primary endpoint of this study will be the degree of attenuation of the late-phase asthmatic response.
In a randomized, placebo-controlled study, the efficacy of inhaled fluticasone propionate (FP), 1000 μg/day on peak expiratory flow (PEF) and bronchial hyper-reactivity in smokers with mild asthma was assessed compared with non-smoking asthmatics. Asthmatics who smoked showed impaired responses to ICS therapy compared with non-smoking asthmatics \[Chalmers, 2002\] and this lack of responsiveness appears to be dose-dependent. When the dose of ICS is increased, the disparity between lung function, rescue inhaler usage and asthma control seen in smokers and non-smokers decreases \[Tomlinson, 2005\].
Interestingly, smoking also affects the ability of ICS to suppress exhaled nitric oxide (eNO) levels in asthmatics \[Horváth, 2004\]. Smoking cessation improves basal lung function but requires at least a year to demonstrate any improvement in Glucocorticoid (GC) responsiveness with respect to morning peak expiratory flow, but not FEV1, after therapy with high-dose oral prednisolone \[Chaudhuri , 2006\].
Smoking asthmatics have more severe disease requiring more therapy, have more hospital admissions and are more likely to die from asthma \[Thomson, 2005\].
Cigarette smoking remains therefore one of the commonest causes of steroid resistance in asthma, however many aspects of the development and restoration of corticosteroid resistance remain unclarified in this population partly due to the paucity of studies performed.
The mechanisms underlying GC resistance in smoking asthmatics are incompletely understood but are thought to include noneosinophilic (often neutrophilic) airway inflammation \[Chalmers, 2001\], impaired corticosteroid receptor function, and/or reduced histone deacetylase activity \[Adcock, 2008\]. In support of these effects of smoking on asthma, animal models show that smoking can increase inflammation in allergic models of asthma and can affect steroid responsiveness.
Tobacco smoke exposure (4 cigarettes/day for 3weeks) had a small neutrophilic effect in mice, whereas ovalbumin exposure had no inflammatory effect in the airways, but increased allergen-specific IgE \[Moerloose, 2006\]. More recently in mouse models, cigarette smoke has been shown to enhance T-helper-(TH)2-driven airway inflammation \[Van Hove , 2008\].
Inhaled allergens are an important trigger of exacerbations in asthma \[Johnston, 2006\].
The airway inflammation induced by inhaled allergens, and the effects of drugs on this airway inflammation, can be studied using an experimental allergen challenge model. All the currently approved drugs used to treat asthma modify, in some way, allergen-induced airway responses. Following inhalation of the appropriate allergen extract, sensitive subjects, i.e. atopic-asthmatics, develop an acute bronchoconstriction which peaks at 20 to 30 minutes post-allergen and lasts for approximately two hours before recovery.
This early response (EAR) reflects mast cell activation and subsequent release of mainly spasmogenic mediators and correlates with the extent of airway inflammation and disease activity \[Grzelewska-Rsymowska, 1995\]. In approximately 50% of patients, the EAR is followed by a late-phase asthmatic response (LAR). This more prolonged airway narrowing is associated with influx of activated inflammatory cells, especially eosinophils, into the airways and represents the more chronic features of asthma, consisting of a prolonged airway narrowing through both bronchospasm and airway inflammation.
The sequelae of the LAR can last several days and up to 3 weeks. Also, the late response has been shown to be associated with an increase in airway hyperresponsiveness (AHR) to stimuli, such as methacholine for several days after allergen challenge \[Hansel, 2002\].
This clinically relevant model of allergic bronchoconstriction has been useful in humans for exploring the time-course of cellular inflammation and the associated physiological changes, particularly related to eosinophils, basophils and dendritic cells \[O'Byrne, 2009\].In non smoking asthmatics, regular treatment with inhaled corticosteroids has been shown to attenuate the early allergic response, perhaps by reducing the number of mast cells in airways \[Gauvreau, 2000\] and to improve the late-phase asthmatic response \[Kidney, 1997; Cockcroft, 1987\].
As previous allergen challenge studies with therapeutic interventions have been conducted only in the population of non-smokers, this study will be the first to examine the allergen challenge response to FP in smoking asthmatics. The primary endpoint of this study will be the degree of attenuation of the late-phase asthmatic response.
Conditions
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Asthma
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
Primary Study Purpose
OTHER
Blinding Strategy
DOUBLE
Participants
Investigators
Study Groups
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3 periods cross-over study
Each subject will receive each intervention BID during a 7 days period. The treatment periods are separated by 14 days washout. The sequence in which the interventions are administered are at random and double blind.
Group Type
PLACEBO_COMPARATOR
100 micrograms Fluticasone propionate
Intervention Type
DRUG
100 micrograms micronized drug blended with lactose in dry powder inhalator
500 micrograms Fluticasone propionate
Intervention Type
DRUG
500 micrograms micronized drug blended with lactose in dry powder inhalator
lactose powder
Intervention Type
DRUG
lactose powder in dry powder device : placebo comparator
Interventions
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100 micrograms Fluticasone propionate
100 micrograms micronized drug blended with lactose in dry powder inhalator
Intervention Type
DRUG
500 micrograms Fluticasone propionate
500 micrograms micronized drug blended with lactose in dry powder inhalator
Intervention Type
DRUG
lactose powder
lactose powder in dry powder device : placebo comparator
Intervention Type
DRUG
Other Intervention Names
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Flixotide
Flixotide
Eligibility Criteria
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Inclusion Criteria
* males and females between 18 and 55 years of age inclusive
* female subject of child-bearing potential and agrees to use one of the contraception methods; or of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
* male subjects with female partners of child-bearing potential must agree to use a contraception method
* body weight ≥50 kg and BMI within the range (18.5-35) kg/m2 (inclusive)
* documented history of bronchial asthma, first diagnosed at least 6 months prior to the first screening visit (according to the BTS guideline 2009), and currently being treated only with prn short-acting inhaled β2-agonist therapy
* current smokers or non-smokers or ex-smokers
* pre-bronchodilator FEV1 \>70% of predicted at screening
* sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20 % fall in FEV1 of \< 8 mg/ml at screening
* able to produce acceptable induced sputum samples
* positive wheal and/or flare reaction (≥ 3 mm relative to negative control) to at least one allergen on skin prick testing at screening or within 12 months of the study start
* screening allergen challenge must demonstrate that the subject experiences both an early and late asthmatic response.
* AST, ALT, alkaline phosphatase and bilirubin \<=1.5xULN
* written informed consent
* able to understand and comply with the study procedures, planned treatment period and other protocol requirements and stated restrictions
* female subject of child-bearing potential and agrees to use one of the contraception methods; or of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
* male subjects with female partners of child-bearing potential must agree to use a contraception method
* body weight ≥50 kg and BMI within the range (18.5-35) kg/m2 (inclusive)
* documented history of bronchial asthma, first diagnosed at least 6 months prior to the first screening visit (according to the BTS guideline 2009), and currently being treated only with prn short-acting inhaled β2-agonist therapy
* current smokers or non-smokers or ex-smokers
* pre-bronchodilator FEV1 \>70% of predicted at screening
* sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20 % fall in FEV1 of \< 8 mg/ml at screening
* able to produce acceptable induced sputum samples
* positive wheal and/or flare reaction (≥ 3 mm relative to negative control) to at least one allergen on skin prick testing at screening or within 12 months of the study start
* screening allergen challenge must demonstrate that the subject experiences both an early and late asthmatic response.
* AST, ALT, alkaline phosphatase and bilirubin \<=1.5xULN
* written informed consent
* able to understand and comply with the study procedures, planned treatment period and other protocol requirements and stated restrictions
Exclusion Criteria
* past or present disease (other than asthma)
* respiratory tract infection and / or exacerbation of asthma within 4 weeks prior the first dose of study drug
* history of life-threatening asthma
* symptomatic with hay fever at screening or predicted to have symptomatic hay fever during the time of the study
* administration of oral or injectable steroids within 5 weeks of the screening visit or intranasal and / or inhaled steroids within 4 weeks of the screening visit
* unable to abstain from other medication, including non-steroidal anti-inflammatory drugs, anti-depressants, anti-histamines, anti-asthma and anti-rhinitis or hay fever medication, other than short acting β2-agonists and paracetamol (up to 4 gram per day) for the treatment of minor ailments (such as headache) from 14 days before screening until the follow-up visit
* unable to abstain from short acting β2-agonists as described in the restriction section of the protocol
* if, after two consecutive administrations of saline, during the allergen challenge at screening, the subject still has a fall of FEV1 of 10%
* a positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result
* clinical significant abnormalities in safety laboratory analysis at screening
* significant abnormality on 12-lead ECG at screening
* the subject is undergoing an allergen desensitisation therapy. Subjects with a positive pre-study drug/alcohol screen
* a history of regular alcohol consumption within 6 months of the screening visit
* a positive test for HIV antibody
* the subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
* history of being unable to tolerate or complete methacholine and / or allergen challenge test
* use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication
* unable to abstain from medication or supplements that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including but not limited to antiretrovirals (protease inhibitors - e.g. ritonavir indinavir, nelfinavir, ritonavir, saquinavir); imidazole and triazole anti-fungals (e.g. ketoconazole, itraconazole) and macrolide antibiotics (e.g. clarithromycin, telithromycin) from screening and throughout the study
* consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication
* history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that contraindicates their participation
* donation of blood or blood products in excess of 500 mL within a 56 day period
* pregnant females at screening or prior to dosing
* lactating females
* unwillingness or inability to follow the procedures outlined in the protocol
* subject is mentally or legally incapacitated
* urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening (for subjects taking part in the non-smokers group of the study)
* respiratory tract infection and / or exacerbation of asthma within 4 weeks prior the first dose of study drug
* history of life-threatening asthma
* symptomatic with hay fever at screening or predicted to have symptomatic hay fever during the time of the study
* administration of oral or injectable steroids within 5 weeks of the screening visit or intranasal and / or inhaled steroids within 4 weeks of the screening visit
* unable to abstain from other medication, including non-steroidal anti-inflammatory drugs, anti-depressants, anti-histamines, anti-asthma and anti-rhinitis or hay fever medication, other than short acting β2-agonists and paracetamol (up to 4 gram per day) for the treatment of minor ailments (such as headache) from 14 days before screening until the follow-up visit
* unable to abstain from short acting β2-agonists as described in the restriction section of the protocol
* if, after two consecutive administrations of saline, during the allergen challenge at screening, the subject still has a fall of FEV1 of 10%
* a positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result
* clinical significant abnormalities in safety laboratory analysis at screening
* significant abnormality on 12-lead ECG at screening
* the subject is undergoing an allergen desensitisation therapy. Subjects with a positive pre-study drug/alcohol screen
* a history of regular alcohol consumption within 6 months of the screening visit
* a positive test for HIV antibody
* the subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
* history of being unable to tolerate or complete methacholine and / or allergen challenge test
* use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication
* unable to abstain from medication or supplements that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including but not limited to antiretrovirals (protease inhibitors - e.g. ritonavir indinavir, nelfinavir, ritonavir, saquinavir); imidazole and triazole anti-fungals (e.g. ketoconazole, itraconazole) and macrolide antibiotics (e.g. clarithromycin, telithromycin) from screening and throughout the study
* consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication
* history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that contraindicates their participation
* donation of blood or blood products in excess of 500 mL within a 56 day period
* pregnant females at screening or prior to dosing
* lactating females
* unwillingness or inability to follow the procedures outlined in the protocol
* subject is mentally or legally incapacitated
* urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening (for subjects taking part in the non-smokers group of the study)
Minimum Eligible Age
18 Years
Maximum Eligible Age
55 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
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GSK Investigational Site
Brussels, , Belgium
Site Status
GSK Investigational Site
London, , United Kingdom
Site Status
Countries
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Belgium
United Kingdom
References
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Adcock IM, Barnes PJ. Molecular mechanisms of corticosteroid resistance. Chest. 2008 Aug;134(2):394-401. doi: 10.1378/chest.08-0440.
Reference Type
BACKGROUND
Chalmers GW, Macleod KJ, Little SA, Thomson LJ, McSharry CP, Thomson NC. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002 Mar;57(3):226-30. doi: 10.1136/thorax.57.3.226.
Reference Type
BACKGROUND
Chalmers GW, MacLeod KJ, Thomson L, Little SA, McSharry C, Thomson NC. Smoking and airway inflammation in patients with mild asthma. Chest. 2001 Dec;120(6):1917-22. doi: 10.1378/chest.120.6.1917.
Reference Type
BACKGROUND
Chaudhuri R, Livingston E, McMahon AD, Lafferty J, Fraser I, Spears M, McSharry CP, Thomson NC. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33. doi: 10.1164/rccm.200510-1589OC. Epub 2006 Apr 27.
Reference Type
BACKGROUND
Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol. 1987 May;79(5):734-40. doi: 10.1016/0091-6749(87)90204-1.
Reference Type
BACKGROUND
Gauvreau GM, Wood LJ, Sehmi R, Watson RM, Dorman SC, Schleimer RP, Denburg JA, O'Byrne PM. The effects of inhaled budesonide on circulating eosinophil progenitors and their expression of cytokines after allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med. 2000 Dec;162(6):2139-44. doi: 10.1164/ajrccm.162.6.2001120.
Reference Type
BACKGROUND
GlaxoSmithKline Document Number GM2003/00619/00 Study ID EL110002. A single-centre, randomised, double-blind, double-dummy, placebo-controlled, 3-period crossover study to evaluate the effect of pre-treatment with repeat doses of GW842470X (6mg inhaled once daily via the Cyclohaler for 7 days) on the allergen induced late asthmatic response in subjects with mild to moderate asthma, using fluticasone propionate (250 mcg twice daily for 7 days) as a positive control. Report Date 24-Jun-2004.
Reference Type
BACKGROUND
GlaxoSmithKline Document Number YM2009/00265/00 Study ID LPA111834. A randomised, double-blind, placebo-controlled, 2-period crossover study to evaluate the effect of treatment with GSK2190915 on the allergen-induced asthmatic response in subjects with mild asthma. Report Date 26-Mar-2010.
Reference Type
BACKGROUND
GlaxoSmithKline Document Number YM2010/00033/00 Study ID SIG110762. A randomised, placebo-controlled, incomplete block, three-way crossover study to evaluate the effect of treatment with repeat inhaled doses of GW870086 on the allergen-induced early and late asthmatic response in subjects with mild asthma. Report Date 10-May-2010.
Reference Type
BACKGROUND
Grzelewska-Rzymowska I, Gondorowicz K, Cieslewicz G, Rozniecki J. [Course of non-specific bronchial reactivity to histamine after bronchospasm induced by allergen challenge in patients with bronchial asthma]. Pneumonol Alergol Pol. 1995;63(5-6):273-80. Polish.
Reference Type
BACKGROUND
Hansel TT, Erin EM, Barnes PJ. The allergen challenge. Clin Exp Allergy. 2002 Feb;32(2):162-7. doi: 10.1046/j.1365-2222.2002.01309.x. No abstract available.
Reference Type
BACKGROUND
Horvath I, Donnelly LE, Kiss A, Balint B, Kharitonov SA, Barnes PJ. Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers. Respiration. 2004 Sep-Oct;71(5):463-8. doi: 10.1159/000080630.
Reference Type
BACKGROUND
Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2006 Mar;117(3):522-43. doi: 10.1016/j.jaci.2006.01.032.
Reference Type
BACKGROUND
Johnston NW, Sears MR. Asthma exacerbations . 1: epidemiology. Thorax. 2006 Aug;61(8):722-8. doi: 10.1136/thx.2005.045161.
Reference Type
BACKGROUND
Kidney JC, Boulet LP, Hargreave FE, Deschesnes F, Swystun VA, O'Byrne PM, Choudry N, Morris MM, Jennings B, Andersson N, Andreasson A, Cockcroft DW. Evaluation of single-dose inhaled corticosteroid activity with an allergen challenge model. J Allergy Clin Immunol. 1997 Jul;100(1):65-70. doi: 10.1016/s0091-6749(97)70196-9.
Reference Type
BACKGROUND
Moerloose KB, Robays LJ, Maes T, Brusselle GG, Tournoy KG, Joos GF. Cigarette smoke exposure facilitates allergic sensitization in mice. Respir Res. 2006 Mar 29;7(1):49. doi: 10.1186/1465-9921-7-49.
Reference Type
BACKGROUND
O'Shaughnessy KM, Wellings R, Gillies B, Fuller RW. Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1472-6. doi: 10.1164/ajrccm/147.6_Pt_1.1472.
Reference Type
BACKGROUND
O'Byrne PM, Gauvreau GM, Brannan JD. Provoked models of asthma: what have we learnt? Clin Exp Allergy. 2009 Feb;39(2):181-92. doi: 10.1111/j.1365-2222.2008.03172.x.
Reference Type
BACKGROUND
Singh D, Petavy F, Macdonald AJ, Lazaar AL, O'Connor BJ. The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Respir Res. 2010 Mar 1;11(1):26. doi: 10.1186/1465-9921-11-26.
Reference Type
BACKGROUND
Thomson NC, Spears M. The influence of smoking on the treatment response in patients with asthma. Curr Opin Allergy Clin Immunol. 2005 Feb;5(1):57-63. doi: 10.1097/00130832-200502000-00011.
Reference Type
BACKGROUND
Tomlinson JE, McMahon AD, Chaudhuri R, Thompson JM, Wood SF, Thomson NC. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax. 2005 Apr;60(4):282-7. doi: 10.1136/thx.2004.033688.
Reference Type
BACKGROUND
Van Hove CL, Moerloose K, Maes T, Joos GF, Tournoy KG. Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance. Respir Res. 2008 May 20;9(1):42. doi: 10.1186/1465-9921-9-42.
Reference Type
BACKGROUND
Cahn A, Boyce M, Mistry S, Musani N, Rambaran C, Storey J, Ventresca P, Michel O. Randomized trial of allergen-induced asthmatic response in smokers and non-smokers: effects of inhaled corticosteroids. Clin Exp Allergy. 2015 Oct;45(10):1531-41. doi: 10.1111/cea.12610.
Reference Type
DERIVED
Study Documents
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Document Type: Dataset Specification
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Annotated Case Report Form
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Statistical Analysis Plan
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Study Protocol
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Individual Participant Data Set
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Clinical Study Report
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentDocument Type: Informed Consent Form
For additional information about this study please refer to the GSK Clinical Study Register
View DocumentRelated Links
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Other Identifiers
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114748
Identifier Type: -
Identifier Source: org_study_id
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