Browsing by Author "Bateman, Eric D"
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- ItemOpen AccessAclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT)(2015-08-02) Bateman, Eric D; Chapman, Kenneth R; Singh, Dave; D’Urzo, Anthony D; Molins, Eduard; Leselbaum, Anne; Gil, Esther GAbstract Background The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT). Methods Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed. Results The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01). Conclusions Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo. Trial registration NCT01462942 and NCT01437397 (ClinicalTrials.gov)
- ItemOpen AccessA blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study(BioMed Central, 2014-01-17) Chapman, Kenneth R; Beeh, Kai-Michael; Beier, Jutta; Bateman, Eric D; D’Urzo, Anthony; Nutbrown, Robert; Henley, Michelle; Chen, Hungta; Overend, Tim; D’Andrea, PeterAbstract Background Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium. Methods In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment. Results 657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0–4 h (AUC0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%). Conclusion In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium. Trial registration ClinicalTrial.gov, NCT01613326
- ItemOpen AccessCigarette smoke and human pulmonary immune responses to mycobacteria(2011) Van Zyl-Smit, Richard Nellis; Dheda, Keertan; Bateman, Eric DRecent epidemiological evidence suggests that up to 15% of worldwide tuberculosis (TB) cases may be attributable to tobacco smoking. The aim of the studies reported here was to gain insights into the effects of exposure to cigarette smoke on human cells that form part of the innate immune system of host defence in the lung. The experiments on the pulmonary effects of cigarette smoke confirm that exposure has a significant effect upon innate host defences. Significant reductions in the production of key cytokines implicated in defences against mycobacteria were observed, not attributable to impairment of mycobacterial uptake by cigarette smoke extract exposure. Furthermore, control of intracellular mycobacterial growth was impaired by cigarette smoke extract exposure.
- ItemOpen AccessComparison of quantitative techniques including Xpert MTB/RIF to evaluate mycobacterial burden(Public Library of Science, 2011) van Zyl-Smit, Richard N; Binder, Anke; Meldau, Richard; Mishra, Hridesh; Semple, Patricia L; Theron, Grant; Peter, Jonathan; Whitelaw, Andrew; Sharma, Suren K; Warren, Robin; Bateman, Eric D; Dheda, KeertanIntroduction: Accurate quantification of mycobacterial load is important for the evaluation of patient infectiousness, disease severity and monitoring treatment response in human and in-vitro laboratory models of disease. We hypothesized that newer techniques would perform as well as solid media culture to quantify mycobacterial burden in laboratory specimens. METHODS: We compared the turn-around-time, detection-threshold, dynamic range, reproducibility, relative discriminative ability, of 4 mycobacterial load determination techniques: automated liquid culture (BACTEC-MGIT-960), [ 3 H]-uracil incorporation assays, luciferase-reporter construct bioluminescence, and quantitative PCR(Xpert -MTB/RIF) using serial dilutions of Mycobacterium bovis and Mycobacterium tuberculosis H37RV. Mycobacterial colony-forming-units(CFU) using 7H10-Middlebrook solid media served as the reference standard. RESULTS: All 4 assays correlated well with the reference standard, however, bioluminescence and uracil assays had a detection threshold ≥1×10 3 organisms. By contrast, BACTEC-MGIT-960 liquid culture, although only providing results in days, was user-friendly, had the lowest detection threshold (<10 organisms), the greatest discriminative ability (1 vs. 10 organisms; p = 0.02), and the best reproducibility (coefficient of variance of 2% vs. 38% compared to uracil incorporation; p = 0.02). Xpert-MTB/RIF correlated well with mycobacterial load, had a rapid turn-around-time (<2 hours), was user friendly, but had a detection limit of ∼100 organisms. CONCLUSIONS: Choosing a technique to quantify mycobacterial burden for laboratory or clinical research depends on availability of resources and the question being addressed. Automated liquid culture has good discriminative ability and low detection threshold but results are only obtained in days. Xpert MTB/RIF provides rapid quantification of mycobacterial burden, but has a poorer discrimination and detection threshold.
- ItemOpen AccessComparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids(BioMed Central, 2014-06-13) Lötvall, Jan; Bateman, Eric D; Busse, William W; O’Byrne, Paul M; Woodcock, Ashley; Toler, William T; Jacques, Loretta; Goldfrad, Caroline; Bleecker, Eugene RBackground: 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 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS. Results: Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint, substantial improvements in lung function were seen with VI (359 ml), SAL (283 ml) and placebo (289 ml). There were no statistically significant treatment differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926) groups and placebo. Both active treatments were well tolerated, with similarly low rates of treatment-related adverse events compared with placebo. No treatment-related serious adverse events occurred. Conclusions: This study failed to show a treatment difference between VI and placebo for the primary endpoint, in the presence of a placebo response of unforeseen magnitude. Because the placebo response was so large, it is not possible to draw meaningful conclusions from the data. The reason for this magnitude of effect is unclear but it may reflect increased compliance with the anti-inflammatory therapy regimen during the treatment period. Trial registration: NCT01181895 at ClinicalTrials.gov.
- ItemOpen AccessCorrection to: Global asthma prevalence in adults: findings from the cross-sectional world health survey(2021-10-08) To, Teresa; Stanojevic, Sanja; Moores, Ginette; Gershon, Andrea S; Bateman, Eric D; Cruz, Alvaro A; Boulet, Louis-PhilippeCorrection to: BMC Public Health 12, 204 (2012) https://doi.org/10.1186/1471-2458-12-204
- ItemOpen AccessThe development and validation of a respiratory guideline for nurses in primary care in South Africa(2006) English, René Glynnis; Bateman, Eric D; Bachmann, MaxThe Practical Aproach to Lung Health in South Africa (P ALSA) initiative aims to improve the diagnosis and management of patients with respiratory diseases in primary care. An algorithm-based syndromic guideline integrating common respiratory diseases for nurses was developed after review of a generic respiratory guideline, medical literature, local policies, and qualitative research.
- ItemOpen AccessDiagnostic, prognostic and therapeutic considerations in primary pulmonary hypertension(1987) Chapman, P J; Benatar, Solomon R; Bateman, Eric DThe diagnosis of primary pulmonary hypertension (PPH) and prediction of its course, whether treated or untreated, presents several problems. These are of particular relevance when selection of patients for, and timing of heart-lung transplantation is being considered. I performed a retrospective study on patients with PPH and chronic large vessel thromboembolic pulmonary hypertension (TPH) seen at Groote Schuur Hospital between 1957 and 1985 in an attempt to: 1. Establish the diagnostic and prognostic value of clinical features, lung function tests, cardiac catheterisation, isotope lung scans and, in the PPH group, response to therapy; 2. Review our experience of the effects of treatment with vasodilators and oral anticoagulants, and the results of heart and lung transplantation in the PPH group; 3. Attempt to identify features which could be used to predict prognosis in PPH; and thereby 4. Define criteria for selecting PPH patients whose prognosis could be improved by heart-lung transplantation.
- ItemOpen AccessEfficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study(2014-11-18) Singh, Dave; Jones, Paul W; Bateman, Eric D; Korn, Stephanie; Serra, Cristina; Molins, Eduard; Caracta, Cynthia; Gil, Esther G; Leselbaum, AnneAbstract Background Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed. Methods In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a. Results At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy. Conclusions Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD. Trial registration ClinicalTrials.gov: NCT01462942 .
- ItemOpen AccessEfficacy and safety of fluticasone furoate 100 μg and 200 μg once daily in the treatment of moderate-severe asthma in adults and adolescents: a 24-week randomised study(BioMed Central, 2014-07-09) Woodcock, Ashley; Lötvall, Jan; Busse, William W; Bateman, Eric D; Stone, Sally; Ellsworth, Anna; Jacques, LorettaBackground: Inhaled corticosteroids are a mainstay of therapy for persistent asthma, but suboptimal adherence with twice-daily use is widespread. Fluticasone furoate (FF) is a new inhaled corticosteroid (ICS) suitable for once-daily dosing in asthma. This study was performed to descriptively assess the efficacy and safety of two doses of FF, with no planned formal statistical hypothesis testing. Methods: This was a 24-week double-blind, multicentre, parallel-group study (NCT01431950). Patients aged ≥ 12 years with moderate-severe persistent asthma and uncontrolled on mid-high dose ICS were stratified by baseline FEV1 and randomised (1:1) to treatment with FF 100 μg or 200 μg once daily in the evening. The primary endpoint was change from baseline trough FEV1 after 24 weeks; secondary and other endpoints included peak expiratory flow (PEF) and rescue-free and symptom-free 24-hour periods over Weeks 1–24, and Asthma Control Test™ (ACT) score at Week 24. A pre-specified subgroup analysis of patients by randomisation strata was performed for the primary and selected secondary and other endpoints. Safety assessments included adverse events, laboratory and vital sign measurements, and change from baseline in 24-hour urinary cortisol at Week 24. Results: With FF 100 μg and 200 μg, least squares mean trough FEV1 improved from baseline by 208 mL and 284 mL, respectively, at Week 24; treatment difference: 77 mL (95% CI: –39, 192). Similar improvements from baseline in rescue- and symptom-free periods, and morning and evening PEF were observed in both groups. Patients were 42% more likely to be well-controlled (ACT score ≥ 20) with FF 200 μg than with FF 100 μg. Slightly more patients receiving FF 200 μg vs. FF 100 μg reported adverse events (63% vs. 59%) and events deemed treatment related (5% vs. <1%). Seven serious adverse events (FF 200 μg 4; FF 100 μg 3) were reported, none of which were deemed treatment related. No clinically relevant effects of either dose on 24-hour urinary cortisol were observed. Conclusion: Improvements from baseline in trough FEV1 were observed after 24 weeks of treatment with both doses of FF, with a numerically greater improvement in FEV1 observed in patients receiving FF 200 μg. Secondary endpoint findings were similar between groups. No safety concerns were identified during the study.
- ItemOpen AccessEfficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease(BioMed Central, 2011-04-26) Jones, Paul W; Rennard, Stephen I; Agusti, Alvar; Chanez, Pascal; Magnussen, Helgo; Fabbri, Leonardo; Donohue, James F; Bateman, Eric D; Gross, Nicholas J; Lamarca, Rosa; Caracta, Cynthia; Gil, Esther GBackground: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/ COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD.
- ItemOpen AccessEfficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial(2014-08-11) O’Byrne, Paul M; Woodcock, Ashley; Bleecker, Eugene R; Bateman, Eric D; Lötvall, Jan; Forth, Richard; Medley, Hilary; Jacques, Loretta; Busse, William WAbstract Background Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy. Methods This 12-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study randomized 248 patients (aged ≥12 years) to once-daily FF 50 mcg administered via the ELLIPTA™a dry powder inhaler or placebo. The primary endpoint was change from baseline in pre-dose evening trough forced expiratory volume in one second (FEV1). Secondary endpoints were change from baseline in percentage of rescue-free 24-h periods (powered), evening and morning peak expiratory flow, symptom-free 24-h periods and withdrawals due to lack of efficacy. Other endpoints included Asthma Control Test™, Asthma Quality of Life Questionnaire and ELLIPTA ease of use questions. Safety was assessed throughout the study. Results There was a significant difference in evening trough FEV1 between FF 50 mcg and placebo (treatment difference: 120 mL; p = 0.012). There was also a significant difference in rescue-free 24-h periods (11.6%; p = 0.004) vs. placebo. There were numerically greater improvements with FF vs. placebo for all remaining secondary endpoints. The incidence of adverse events was lower with FF (31%) than with placebo (38%); few were treatment-related (FF 50 mcg: n = 1, <1%; placebo: n = 4, 3%). Conclusion FF 50 mcg once daily significantly improved FEV1 and percentage of rescue-free 24-h periods experienced over 12 weeks vs. placebo, and was well tolerated. Trial registration www.clinicaltrials.gov , registration number: NCT01436071
- ItemOpen AccessEfficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial(BioMed Central Ltd, 2011) Woodcock, Ashley; Bateman, Eric D; Busse, William W; Lotvall, Jan; Snowise, Neil G; Forth, Richard; Jacques, Loretta; Haumann, Brett; Bleecker, Eugene RBACKGROUND: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma. METHODS: Asthma patients maintained on ICS for [greater than or equal to] 3 months with baseline morning forced expiratory volume in one second (FEV1) 50-80% of predicted normal value and FEV1 reversibility of [greater than or equal to] 12% and [greater than or equal to] 200 ml were eligible. The primary endpoint was mean change from baseline FEV1 at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV1. RESULTS: A total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV1 compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV1 at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV1 than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups. CONCLUSIONS: FF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated once-daily treatment for mild-to-moderate asthma.TRIAL REGISTRATION:NCT00398645
- ItemOpen AccessEfficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial(BioMed Central, 2011-12-01) Woodcock, Ashley; Bateman, Eric D; Busse, William W; Lötvall, Jan; Snowise, Neil G; Forth, Richard; Jacques, Loretta; Haumann, Brett; Bleecker, Eugene RBackground: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebocontrolled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma. Methods: Asthma patients maintained on ICS for ≥ 3 months with baseline morning forced expiratory volume in one second (FEV1) 50-80% of predicted normal value and FEV1 reversibility of ≥ 12% and ≥ 200 ml were eligible. The primary endpoint was mean change from baseline FEV1 at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV1. Results: A total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV1 compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV1 at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV1 than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups. Conclusions: FF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated oncedaily treatment for mild-to-moderate asthma. Trial registration: NCT00398645
- ItemOpen AccessFluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma(BioMed Central Ltd, 2011) Woodcock, Ashley; Bleecker, Eugene R; Busse, William W; Lotvall, Jan; Snowise, Neil G; Frith, Lucy; Jacques, Loretta; Haumann, Brett; Bateman, Eric DBACKGROUND: Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients. METHODS: Patients with moderate asthma (age [greater than or equal to] 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of [greater than or equal to] 12% and [greater than or equal to] 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for [greater than or equal to] 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 mug OD, FF or FP 100 mug BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 mug OD and FF 100 mug BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed. RESULTS: The intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 mug OD to be non-inferior (pre-defined limit -110 ml) to FF 100 mug BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p [less than or equal to] 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 mug OD, 0.75; 100 mug BD, 0.84; p [less than or equal to] 0.02). CONCLUSIONS: FF 200 mug OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.TRIAL REGISTRATION:Clinicaltrials.gov; NCT00766090.
- ItemOpen AccessHelsinki by nature: The Nature Step to Respiratory Health(2019-10-30) Haahtela, Tari; von Hertzen, Leena; Anto, Josep M; Bai, Chunxue; Baigenzhin, Abay; Bateman, Eric D; Behera, Digambar; Bennoor, Kazi; Camargos, Paulo; Chavannes, Niels; de Sousa, Jaime C; Cruz, Alvaro; Do Céu Teixeira, Maria; Erhola, Marina; Furman, Eeva; Gemicioğlu, Bilun; Gonzalez Diaz, Sandra; Hellings, Peter W; Jousilahti, Pekka; Khaltaev, Nikolai; Kolek, Vitezslav; Kuna, Piotr; La Grutta, Stefania; Lan, Le T T; Maglakelidze, Tamaz; Masjedi, Mohamed R; Mihaltan, Florin; Mohammad, Yousser; Nunes, Elizabete; Nyberg, Arvid; Quel, Jorge; Rosado-Pinto, Jose; Sagara, Hironori; Samolinski, Boleslaw; Schraufnagel, Dean; Sooronbaev, Talant; Tag Eldin, Mohamed; To, Teresa; Valiulis, Arunas; Varghese, Cherian; Vasankari, Tuula; Viegi, Giovanni; Winders, Tonya; Yañez, Anahi; Yorgancioğlu, Arzu; Yusuf, Osman; Bousquet, Jean; Billo, Nils EAbstract Background The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. Results The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking “nature” to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. Conclusions In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory.
- ItemOpen AccessHut lung : a study of domestically acquired pneumoconiosis in rural women(1987) Grobbelaar, Johannes P; Bateman, Eric DPneumoconiosis in rural Transkeian women termed "Transkei Silicosis" has been thought to be caused by silica inhaled while grinding maize by traditional methods (Palmer and Daynes, 1967). This study was undertaken to investigate the features and causes of hut lung. The range of clinical, radiologic, histologic, pulmonary physiologic and broncho-alveolar lavage features in patients meeting the following criteria was assessed: i) rural women practising traditional cooking methods ii) with a diffuse nodularity on chest x-ray iii) and lung biopsy evidence of pneumoconiosis iv) and without occupational exposure v) or evidence of active tuberculosis. Smoke and dust levels were measured in rural dwellings during cooking and maize grinding and ground maize and grinding rocks were analysed. 25 patients were studied. 17 were non-smokers, 5 were pipe smokers and 3 smoked 10 or less cigarettes per day. 7 had evidence of previous tuberculosis. The radiological findings ranged from a diffuse fine miliary pattern through coarse nodules with coalescence, to extensive fibrosis resembling PMF. The histologic features revealed simple "anthracosis" in 12, anthracosis with macules in 6 and mixed dust fibrosis in 7, of which 2 had silicotic nodules and 1 PMF. No such findings were observed in the control lung biopsy specimens obtained at post-mortem from city dwelling Xhosa females. Mild to moderate airflow limitation (defined as an FEV1/FVC ratio of < 65% and/or RV> 145% of predicted) was present in 73% while a reduced T'LCO (< 80% predicted) was found in 76% of the patients. Cell numbers and differential counts in BAL fluid were normal but> 80% of the macrophages were heavily laden with inorganic inclusions. The mean smoke level during indoor open fire cooking was 30mg/m³. Respirable dust and quartz concentrations ranging from 3,03 to 5, 82mg/m³ and 0,097 to 0,186mg/m³ respectively were found during hand grinding with sandstone (100% quartz), but were lower (ranging from 2,62 to 3,40mg/m³ and 0,024mg/m³ respectively) when non-quartz containing dolerite was used. Calculated cumulative equivalent time-weighted average respirable dust concentrations were shown to be similar to those found in an average South African gold mine while calculated equivalent respirable quartz concentrations were well below those found in the worst exposed gold miners and well within the recommended threshold limit values of the National Institute for Occupational Safety and Health (NIOSH) and the World Health Organisation (WHO). Respirable quartz exposure alone was not sufficient to explain the changes found. Respirable non-quartz containing nuisance dust and intense smoke exposure were shown to be significant. It was concluded that: i) hut lung can be defined as a domestic pneumoconiosis that occurs in rural women who practise primitive cooking methods ii) hut lung typically occurs in rural maize grinding Transkeian women but can occur in other rural women iii) there is a wide clinical, spectrum radiological and histologic iv) the pulmonary physiological changes are predominantly those of airflow limitation with some CO transfer factor reduction v) cigarette and pipe smoking do not contribute to the aetiology or pulmonary physiological abnormalities vi) the bronchoalveolar lavage features may help differentiate this condition from miliary tuberculosis vi) the aetiology of hut lung is multifactorial with exposure to respirable quartz and non-quartz containing dust together with smoke particles from biomass fuelled fires all playing a significant role while previous tuberculosis may be a contributing factor.
- ItemOpen AccessOverall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps(BioMed Central, 2011-12-01) Bateman, Eric D; Harrison, Tim W; Quirce, Santiago; Reddel, Helen K; Buhl, Roland; Humbert, Marc; Jenkins, Christine R; Peterson, Stefan; Östlund, Ollie; O'Byrne, Paul M; Sears, Malcolm R; Eriksson, Göran SBackground: 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® Turbuhaler®) 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 b2-agonist (ICS/LABA) (plus short-acting b2-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.
- ItemOpen AccessPneumonia in HIV-infected children admitted to hospital in Cape Town, South Africa(2000) Zar, Heather; Hussey, Gregory; Bateman, Eric DThere is little information on the aetiology and outcome of HIV-associated pneumonia in African children and no comprehensive data from South Africa. Studies of HIV-infected adult in Africa reported that the spectrum of pulmonary disease differs from that of developed countries with tuberculosis and pyogenic pneumonia predominating and Pneumocystis carinii pneumonia (PCP) occurring uncommonly. Knowledge of the aetiology and outcome of pneumonia is important for the development of paediatric management guidelines and of policies for allocation of resources especially in South Africa, where the HIV pandemic has resulted in increasing numbers of HIV-positive children requiring admission to hospital or intensive care units for pneumonia. Furthermore in countries with limited resources, development of cost effective diagnostic procedures to investigate the aetiology of pneumonia is necessary.
- ItemOpen AccessRespiratory symptoms and chronic obstructive pulmonary disease : prevalence and risk factors in a predominantly low-income urban area of Cape Town, South Africa(2006) Jithoo, Anamika; Bateman, Eric D; White, Neil; Burney, PeterThe continuing worldwide increase in the incidence of chronic obstructive pulmonary disease (COPD) has led to international initiatives to improve surveillance and identify preventable risk factors for this and related chronic lung diseases. The studies reported here aimed to examine the prevalence and risk factors for respiratory symptoms and COPD; to introduce and test surveillance methodologies; and to inform treatment and control measures for this disease. The Lung Health Survey 2002 sampled 3512 individuals aged ≥ 15 years from an urban population of 36,334 in the predominantly low-income area of Ravensmead and Uitsig, Cape Town, South Africa. Information on respiratory symptoms, risk factors and healthcare utilisation was collected using a respiratory questionnaire which included questions that had been validated elsewhere. In 2005, a subsample of 960 persons aged ≥ 40 years participated in the Burden of Obstructive Lung Disease (BOLD) study comprised of a questionnaire and pre and postbronchodilator spirometry, in order to assess the prevalence of COPD. A high prevalence of respiratory symptoms of 38.3% was reported. Tobacco smoking showed a consistent positive association with chronic bronchitis, wheeze, dyspnoea and cough. Strong associations with cannabis smoking, pulmonary tuberculosis, occupational exposures and low socioeconomic status were found. The association of cannabis smoking with respiratory symptoms suggest that it may be a risk factor for COPD. The BOLD study revealed an exceptionally high prevalence of COPD in both men and women aged 40 years and older (29% and 20%, respectively) reflecting the very high prevalence of smoking in both sexes in the test area. The majority of those affected had moderate to severe disease, that is, symptoms with spirometric impairment (GOLD Stage II and higher). Even non-smoking women had a comparatively high prevalence of CO PO (12.6%), attributable to other risk factors such as tuberculosis and occupational exposures. Previous pulmonary tuberculosis was shown to be a strong predictor of COPD, which warrants further study. Review of healthcare utilisation confirmed significant under-recognition and under-treatment within local health services. These results confirm the need to prioritise preventative and treatment strategies for obstructive lung disease in South Africa.