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Sökning: WFRF:(O'Byrne Paul M.)

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1.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Diamant, Zuzana, et al. (författare)
  • Inhaled allergen bronchoprovocation tests.
  • 2013
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 132:5, s. 1045-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell-driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications.
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  • Satia, Imran, et al. (författare)
  • Emergency department visits and hospitalisations for asthma, COPD and respiratory tract infections : what is the role of respiratory viruses, and return to school in September, January and March?
  • 2020
  • Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma exacerbations increase in September coinciding with children returning to school. The aim of this study was to investigate whether this occurs 1) for COPD and respiratory tract infections (RTIs); 2) after school resumes in January and March; and 3) identify which viruses may be responsible.Methods: Emergency department (ED) visits and admissions for asthma, COPD and RTIs and the prevalence of viruses in Ontario, Canada were analysed daily between 2003 and 2013. ED visits and admissions were provided by the Canadian Institute for Health Information. Viral prevalence was obtained from the Centre for Immunisation and Respiratory Infectious Diseases.Results: ED visits and admissions rates demonstrated a biphasic pattern. Lowest rates occurred in July and August and the highest rates in September for asthma, and after December for COPD and RTI. The increase in rates for 30 days before and after school return in September was greatest for children with asthma <15 years (2.4-2.6×). Event rates fell after school return in January for all three conditions ranging from 10-25%, and no change followed March break for asthma and COPD. Human rhinovirus was prevalent in summer with a modest relationship to asthma rates in September. The prevalence of respiratory syncytial virus, influenza A and coronavirus was associated with sustained event rates for COPD and RTIs.Conclusions: Asthma, COPD and RTIs increase in September but do not occur after return to school in January and March. Human rhinovirus is associated with ED visits and admissions only in September.
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  • Bateman, Eric D., et al. (författare)
  • Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps
  • 2011
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART (R) Turbuhaler (R)) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4. Methods: This is a post hoc analysis of the results of five large clinical trials (> 12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined. Results: At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) (plus short-acting beta(2)-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps. Conclusions: BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.
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  • Bateman, Eric D., et al. (författare)
  • Overall asthma control: The relationship between current control and future risk
  • 2010
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 125:3, s. 600-608
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood. Objective: This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler*) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations. Methods: The percentage of patients with Global Initiative for Asthma defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting beta(2)-agonist (LABA), and higher dose ICS/LABA plus short-acting beta(2)-agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies. Results: The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (>= 80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy. Conclusions: Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control. (J Allergy Clin Immunol 2010;125:600-8.)
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  • Duong, MyLinh, et al. (författare)
  • Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma.
  • 2008
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 133:2, s. 404-11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time. CONCLUSIONS: These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs. Trial registration: clinicaltrial.gov; Identifier: NCT00525772.
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  • Lötvall, Jan, 1956, et al. (författare)
  • Comparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids.
  • 2014
  • Ingår i: Journal of negative results in biomedicine. - : Springer Science and Business Media LLC. - 1477-5751. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1second after 12weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS.
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  • O'Byrne, Paul M, et al. (författare)
  • Beta2 deja vu.
  • 2006
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 129:1, s. 3-5
  • Tidskriftsartikel (refereegranskat)
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  • O'Byrne, Paul M, et al. (författare)
  • Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma.
  • 2014
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 43:3, s. 773-82
  • Tidskriftsartikel (refereegranskat)abstract
    • The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV₁) weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV1 and wmFEV₁ versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.
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  • O'Byrne, Paul M, et al. (författare)
  • Severe exacerbations and decline in lung function in asthma.
  • 2009
  • Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 179:1, s. 19-24
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma.
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