Montelukast or salmeterol combined with an inhaled steroid in adult asthma

DEFF Research Database (Denmark)

Bjermer, L; Bisgaard, H; Bousquet, J

2000-01-01

, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare......, asthma attacks, overnight asthma symptoms, and morning peak expiratory flow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-specific quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical......Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add...

Extrafine Beclomethasone/formoterol compared to Fluticasone/salmeterol Combination Therapy in COPD

DEFF Research Database (Denmark)

Singh, D.; Nicolini, G.; Bindi, E.

2014-01-01

Background: The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients. Methods: The trial was a 12-week multicentre, randomised, double-blind, double dummy study......; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 mu g or FP/S 500/50 mu g twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre- dose...... in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations. Results: BDP/FF was equivalent...

Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol and cigarette smoke

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Dorscheid Delbert R

2007-11-01

Full Text Available Abstract The toll-like receptors (TLRs are a key component of host defense in the respiratory epithelium. Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations. We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged. Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression. We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease. Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts. Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein. The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS. Stimulation with salmeterol (10-6 M caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect. The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression. Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.

Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry

International Nuclear Information System (INIS)

Ali, Hassan Refat H.; Edwards, Howell G.M.; Hargreaves, Michael D.; Munshi, Tasnim; Scowen, Ian J.; Telford, Richard J.

2008-01-01

Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting β-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488-1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectroscopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control

Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry

Energy Technology Data Exchange (ETDEWEB)

Ali, Hassan Refat H. [Chemical and Forensic Sciences/University Analytical Centre, School of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP (United Kingdom); Edwards, Howell G.M. [Chemical and Forensic Sciences/University Analytical Centre, School of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP (United Kingdom)], E-mail: H.G.M.Edwards@bradford.ac.uk; Hargreaves, Michael D.; Munshi, Tasnim; Scowen, Ian J.; Telford, Richard J. [Chemical and Forensic Sciences/University Analytical Centre, School of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP (United Kingdom)

2008-07-14

Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting {beta}-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488-1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectroscopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control.

Which inhaled corticosteroid and long-acting β-agonist combination is better in patients with moderate-to-severe asthma, a dry powder inhaler or a pressurized metered-dose inhaler?

Science.gov (United States)

Muraki, Masato; Gose, Kyuya; Hanada, Soichiro; Sawaguchi, Hirochiyo; Tohda, Yuji

2017-11-01

Two main types of devices are used to facilitate the administration of inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) in combination, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). There are few reports comparing the effects of the two devices, and it is unknown which should be recommended for asthma patients with given sets of characteristics. In the current study, the beneficial effects and side effects associated with DPIs and pMDIs were compared, and the question of which device should be recommended for asthma patients was investigated. A prospective, randomized, crossover, comparative study in adult outpatients with asthma was conducted using salmeterol/fluticasone propionate combination (SFC) 50 μg/250 μg, one inhalation of Adoair ® 250 Diskus ® twice daily or two inhalations of Adoair ® 125 Aerosol twice daily, for 8 weeks. Questionnaires, exhaled nitric oxide (FeNO) tests and pulmonary function tests were administered after the use of each device for 8 weeks, and the results derived from each device were compared. Sixty-eight subjects were included in the final analysis. There were no significant differences between quality-of-life scores, FeNO, spirometry test results and forced oscillation results. With regard to patient preferences, 57.4% preferred the Adoair ® Aerosol and 35.3% preferred the Adoair ® Diskus ® , as determined via the comparative evaluation questionnaire. Although DPI prescription accounts for the predominant market share of combined ICS/LABA in Japan, patients preferred a pMDI device to a DPI device. Compared to DPIs, pMDIs may be the preferential choice for patients with asthma.

Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice

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Ledford Dennis

2006-05-01

Full Text Available Abstract Background Respiratory syncytial virus (RSV infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation. Methods Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP and salmeterol (Sal alone versus FP plus Sal (FPS on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR, inflammation and RSV titers were examined. Results The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal. Conclusion Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

Stimulus-selective regulation of human mast cell gene expression, degranulation and leukotriene production by fluticasone and salmeterol.

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Adriana Catalli

Full Text Available Despite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2, we studied the effects of fluticasone propionate (FP and salmeterol (SM, on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM, SM (1 µM, alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P<.05. Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05. As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF, CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05. Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma.

Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.

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Rabe, Klaus F; Fabbri, Leonardo M; Israel, Elliot; Kögler, Harald; Riemann, Kathrin; Schmidt, Hendrik; Glaab, Thomas; Vogelmeier, Claus F

2014-01-01

The effect of β2-adrenergic receptor (ADRB2) polymorphisms on the treatment response to longacting bronchodilators in chronic obstructive pulmonary disease (COPD) is unclear. We aimed to establish whether ADRB2 polymorphisms differentially affected COPD exacerbation outcomes in response to tiotropium versus salmeterol. We did a prespecified analysis of the ADRB2 polymorphisms Arg16Gly and Gln27Glu within the 1 year randomised, double-blind, double-dummy, parallel-group Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, comparing the effects of treatment with tiotropium or salmeterol on exacerbations in 7376 patients with COPD. One blood sample was collected for pharmacogenetic testing from each patient who elected to participate in the substudy. Random assignment of patients to treatment groups was not stratified according to genotypes. Genomic DNA was extracted from whole-blood specimens and samples were genotyped for the two SNPs, rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu). All assays were done in technical duplicates and 10% of samples that were randomly chosen were repeated as technical duplicates in a second independent genotyping process. Our primary endpoint was the risk of a first exacerbation of COPD based on time to first exacerbation data. An exacerbation of COPD was defined as the increase or new onset of more than one symptom of COPD (cough, sputum, wheezing, dyspnoea, or chest tightness), with at least one of the symptoms lasting for 3 days or more and needing treatment with antibiotics or systemic glucocorticoids (moderate exacerbations), or admission to hospital (severe exacerbations). POET-COPD is registered with ClinicalTrials.gov, number NCT00563381. 5125 patients gave informed consent for genotyping. The distributions of ADRB2 genotypes were well matched among groups. Polymorphisms at aminoacid 27 did not affect exacerbation outcomes. In the salmeterol group, patients with Arg16Arg genotype had a significantly reduced

Agglomerate properties and dispersibility changes of salmeterol xinafoate from powders for inhalation after storage at high relative humidity.

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Das, Shyamal; Larson, Ian; Young, Paul; Stewart, Peter

2009-06-28

This study investigated changes in agglomeration and the mechanism of dispersibility decrease of salmeterol xinafoate (SX) from SX-lactose mixtures for inhalation after storage at 75% RH for 3 months. The dispersibility, PSD and in situ PSD of aerosol plumes of SX alone and SX-coarse lactose (CL) mixtures containing 0, 5, 10 and 20% micronized lactose (ML) before and after storage were determined by a Next Generation Impactor (NGI), a Mastersizer 2000 and a Spraytec, respectively. The PSD of ML increased after storage at 75% RH, but dispersibility of SX using the stored ML increased. After storage, the %SX of the mixture containing 20% ML (M20F) significantly increased (Pagglomerates, probably occurring through enhanced capillary interaction and/or solid bridging of ML, entrapping and preventing the release of SX particles.

Intra-individual variability in the urine concentrations of inhaled salmeterol in male subjects with reference to doping analysis – impact of urine specific gravity correction

DEFF Research Database (Denmark)

Hostrup, Morten; Kalsen, Anders; Hemmersbach, Peter

2012-01-01

and a-hydroxysalmeterol during visits one and two were 12.6 and 21.8%, respectively. The intra-individual variability of salmeterol and a-hydroxysalmeterol in the urine concentrations were significantly higher when uncorrected for USG with 43.0 and 43.7% versus 20.4% (p...Since 2010, the World Anti-Doping Agency (WADA) has introduced urinary thresholds for some beta2-agonists. In doping analysis urine samples of beta2-agonists are not corrected for the Urine Specific Gravity (USG) by the WADA laboratories. Several studies have observed high differences in the urine...

Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures for inhalation.

Science.gov (United States)

Adi, Handoko; Larson, Ian; Chiou, Herbert; Young, Paul; Traini, Daniela; Stewart, Peter

2006-11-01

The study investigated the role of agglomeration and the effect of fine lactose size on the dispersion of salmeterol xinafoate (SX) from SX-lactose mixtures for inhalation. Particle size distributions were characterised by Malvern Mastersizer S, Aerosizer and Spraytec, and imaging conducted by scanning electron microscopy (SEM). Inter-particulate adhesion was quantified by atomic force microscopy. Deposition of SX was measured using a twin stage impinger. SX was analysed using validated high-performance liquid chromatography method (r(2)=1.0, CV=0.4-1.0%). Addition of fine lactose with a volume median diameter (VMD) of 7.9 microm to a SX-lactose carrier and carrier-free mixture resulted in significantly better dispersion (16.8% for 20% added fine lactose) than fractions with VMD of 3.0, 17.7 and 33.3 microm (less than 9.1% for 20% fine lactose). Using the carrier-free mixtures, particle sizing of the aerosol cloud using the Spraytec, coupled with the application of the Aerosizer using differing dispersion energies and SEMs of the samples, indicated that an open packed, agglomerate structure improved SX dispersion. The highest extent of SX dispersion occurred when SX and fine lactose were detached from the surface, usually in the form of loose agglomerates. The outcomes of this research demonstrated how agglomerate structure influenced dispersion and the key role of fine lactose particle size in SX dispersion from mixtures for inhalation.

Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast in childhood asthma: A prospective, randomized, double-blind, double-dummy, parallel-group study

DEFF Research Database (Denmark)

Maspero, Jorge; Guerra, Frances; Cuevas, Francisco

2008-01-01

BACKGROUND: Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma. OBJECTIVE: This study, the PEdiatric Asthma Control Evaluation (PEACE......), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children. METHODS: Children with asthma (forced expiratory volume in 1 second [FEV(1)] 55%-80% predicted; reversibility >or=12%) aged 6 to 14 years who were receiving only short-acting beta(2)-agonists...... in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations. RESULTS: Of 607 patients screened, 548...

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

Science.gov (United States)

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

Resumé diskuse

Czech Academy of Sciences Publication Activity Database

Kubínová, Marie; Praks, Vítězslav

2005-01-01

Roč. 53, č. 5 (2005), s. 683-687 ISSN 0009-0468. [Literatura jako text mezi texty. Praha, 8. 6. 2004] R&D Projects: GA ČR(CZ) GA405/03/0416 Institutional research plan: CEZ:AV0Z90560517 Keywords : semiotics Subject RIV: AJ - Letters, Mass-media, Audiovision

Application of mechanical embolectomy in acute ischemic stroke

International Nuclear Information System (INIS)

Lu Haitao; Li Minghua; Zhao Jungong

2008-01-01

Acute ischemic stroke is a common disease serevely threatening the public health. The main management involves intravenous thrombolysis, intra-arterial thrombolysis and mechanical embolectomy. Recently, endovascular mechanical embolectomy is attracted more attention because it provides a good outcome for patients either ineligible not responsible for IV thrombolytic therapy. The article reviews the relative aspects with summerization in this field. (authors)

LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD

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Zhong N

2015-06-01

Full Text Available Nanshan Zhong,1 Changzheng Wang,2 Xiangdong Zhou,3 Nuofu Zhang,1 Michael Humphries,4 Linda Wang,4 Chau Thach,5 Francesco Patalano,6 Donald Banerji5On behalf of the LANTERN Investigators 1State Key Laboratory of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 2Institute of Respiratory Disease, Xin Qiao Hospital, 3Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing City, Chongqing, 4Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 6Novartis Pharma AG, Basel, SwitzerlandBackground: The current Global initiative for chronic Obstructive Lung Disease (GOLD treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA/long-acting muscarinic antagonist (LAMA dual bronchodilator, QVA149 (indacaterol/glycopyrronium, as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC, in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.Methods: In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1 to QVA149 110/50 µg once daily or SFC 50/500 µg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1 at week 26.Results: Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [∆]=75 mL; P<0.001. QVA149 demonstrated a statistically significant

Akademický portál CoolCite

Czech Academy of Sciences Publication Activity Database

Skovajsa, Marek

2010-01-01

Roč. 11, č. 4 (2010), s. 18 ISSN 1210-9525. [Akademický portál CoolCite. Prezentace a diskuse. Praha, 01.02.2010] Institutional research plan: CEZ:AV0Z70280505 Keywords : scientometrics * academic performance measurement * academic portals Subject RIV: AO - Sociology, Demography

Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis

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Vogelmeier C

2016-12-01

Full Text Available Claus Vogelmeier,1 Nanshan Zhong,2 Michael J Humphries,3 Karen Mezzi,4 Robert Fogel,5 Giovanni Bader,4 Francesco Patalano,4 Donald Banerji5 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL, Marburg, Germany; 2State Key Laboratory, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 3Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Background: Indacaterol/glycopyrronium (IND/GLY is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D patients with moderate-to-severe COPD.Patients and methods: Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 µg/50 µg or twice-daily SFC 50 µg/500 µg. End points were pre-dose trough forced expiratory volume in one second (FEV1, standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0–12 hours, peak FEV1, peak forced vital capacity (FVC, pre-dose trough FVC, Transition Dyspnea Index (TDI total score, St George’s Respiratory Questionnaire total score, rescue medication use and safety.Results: A total of 1,263 patients were classified as either GOLD B (n=809 or GOLD D (n=454. At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the

Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life

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Williams Angela E

2007-07-01

Full Text Available Abstract Background Improving patients' health-related quality of life (HRQoL is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP and an adjustable maintenance dosing (AMD regimen of formoterol/budesonide (FOR/BUD where treatment is adjusted based on symptoms [SAM40056]. Methods A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS plus a long-acting β2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4. For Weeks 5–52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP. Results The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034 and the annual exacerbation rate was significantly lower (47%; p = 0.008 with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52. However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively. The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049; a trend for this

Aerosol particle size does not predict pharmacokinetic determined lung dose in children

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Chawes, Bo L K; Vindfeld, Signe

2013-01-01

In vitro measures of aerosol particles size, such as the fine particle mass, play a pivotal role for approval of inhaled anti-asthmatic drugs. However, the validity as a measure of dose to the lungs in children lacks evidence. In this study we investigated for the first time the association between...... an in vivo estimate of lung dose of inhaled drug in children and the corresponding particle size segments assessed ex vivo. Lung dose of fluticasone propionate after inhalation from a dry powder inhaler (Diskus®) was studied in 23 children aged 4-7 and 12-15 years with mild asthma. Six-hour pharmacokinetics...... was assessed after single inhalation. The corresponding emitted mass of drug in segments of aerosol particle size was assessed ex vivo by replicating the inhalation flows recorded by transducers built into the Diskus® inhaler and re-playing them in a breathing simulator. There was no correlation between any...

EFFECT OF BRONCHODILATORS ON HEART RATE VARIABILITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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H. H. Shugushev

2015-12-01

Full Text Available Aim. To study effect of long-acting theophylline (Theotard, KRKA and combination of salmeterol and fluticasone (Seretide, GlaxoSmithKline on heart rhythm variability (HRV and number of arrhythmic episodes in patients with chronic obstructive pulmonary disease (COPD.Material and methods. 144 patients with COPD and 35 patients of control group were examined. The analysis of HRV and Holter monitoring were made f on 2th and 14th days.Results. Treatment with both drugs led to increase in power of low- and high frequencies and their ratio (LF/HF, decrease in rate of supraventricular and ventricular arrhythmias. Theophylline therapy raised in a number of single and pair supraventricular extrasystoles. Treatment with combination of salmeterol and fluticasone did not change a number of extrasystoles.Conclusion. Combination of salmeterol and fluticasone is more preferable as a broncholytic therapy for patients with COPD and heart rhythm disorders.

Comparison of efficacy of long-acting bronchodilators in emphysema dominant and emphysema nondominant chronic obstructive pulmonary disease

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Fujimoto K

2011-04-01

Full Text Available Keisaku Fujimoto1, Yoshiaki Kitaguchi2, Shintaro Kanda2, Kazuhisa Urushihata2, Masayuki Hanaoka2, Keishi Kubo21Department of Biomedical Laboratory Sciences, 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, JapanBackground: The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β2 agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD.Methods: Seventy-two patients with stable COPD treated with tiotropium (n = 41 or salmeterol (n = 31 were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George’s Respiratory Questionnaire (SGRQ before and 2–3 months following treatment with tiotropium or salmeterol. They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed.Results: Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype. Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes.Conclusion: These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further

Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids.

Science.gov (United States)

Townley, Robert G; Gendapodi, Pradeep R; Qutna, Nidal; Evans, Joseph; Romero, Francisco A; Abel, Peter

2009-03-01

Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists. The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease

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Asai K

2015-04-01

Full Text Available Kazuhisa Asai,1 Akihiro Kobayashi,2 Yukio Makihara,3 Malcolm Johnson4 1Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; 2Biomedical Data Sciences, 3Medical Affairs Respiratory Department, GlaxoSmithKline, Tokyo, Japan; 4Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250 in Japanese patients with chronic obstructive pulmonary disease (COPD. Patients and methods: Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26 or placebo (n=26 for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum, lung function, and health status (COPD Assessment Test [CAT] questionnaire were measured. Results: Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum, lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250 and n=10 (placebo. However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250 and 1.3% (placebo decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically

Adesão ao tratamento de manutenção em asma (estudo ADERE Compliance with maintenance treatment of asthma (ADERE study

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José Miguel Chatkin

2006-08-01

Full Text Available OBJETIVO: Avaliar a adesão ao tratamento preventivo de asma persistente moderada e grave. MÉTODOS: Médicos de vários Estados do país foram contactados para selecionar asmáticos persistentes moderados ou graves, maiores de doze anos. Os pacientes receberam salmeterol/fluticasona 50/250 µg diskus durante 90 dias (sendo orientados a retornarem as embalagens ao final do estudo para conferência da dosagem total utilizada. Receberam telefonemas da equipe do estudo no início e ao final de 90 dias para que fosse avaliada a adesão. Foi considerado como aderente ao tratamento o asmático que utilizou no mínimo 85% das doses prescritas. As variáveis estudadas foram sexo, idade, cor, estado civil, escolaridade, tabagismo atual, outras atopias, co-morbidades, gravidade da asma, uso de outras medicações e número de hospitalizações por asma. RESULTADOS: Foram incluídos 131 pacientes oriundos de quinze estados, com taxa geral de adesão de 51,9%. Houve diferença significativa na adesão quanto à gravidade da asma (maior adesão nos casos graves; p = 0,02. Não houve diferença estatisticamente significativa nas demais variáveis. CONCLUSÃO: A taxa geral de adesão ao tratamento de manutenção da asma foi baixa.OBJECTIVE: To determine the rate of compliance with preventive treatment of moderate and severe persistent asthma. METHODS: Physicians at various medical centers across the country were invited to nominate patients for participation in the study. Inclusion criteria were being over the age of 12 and presenting moderate or severe persistent asthma. Participating patients received salmeterol/fluticasone 50/250 µg by dry powder inhaler for 90 days and were instructed to return the empty packages at the end of the study as a means of determining the total quantity used. In order to evaluate compliance, a member of the research team contacted each patient via telephone at the study outset and again at the end of the 90-day study period

Salmeterol Oral Inhalation

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... your medications or monitor you carefully for side effects.tell your doctor if you have or have ever had irregular heartbeat, high blood pressure, hyperthyroidism (overactive thyroid), diabetes, seizures, or liver or heart ...

Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity.

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Bosak, Anita; Knežević, Anamarija; Gazić Smilović, Ivana; Šinko, Goran; Kovarik, Zrinka

2017-12-01

We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K i constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.

Effectiveness of the different methods of inhalation drugs delivery in children with bronchial asthma

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S.M. Nedelska

2017-02-01

Full Text Available Aim of the work — to evaluate the effectiveness of inhalation technique when using different types of inhalers (dry powder inhalers — Turbuhaler, Diskus, metered-dose inhalers, breath-actuated inhalers — Easyhaler. Materials and methods. 45 patients aged 6–17 years underwent the evaluation of inhalation technique accuracy with the use of In-Check-Dial — apparatus, which imitates the airway resistance that should be overcome during inspiration through different inhaler types, and measure inspiration velocity. Incidence of mistakes was studied in different age groups. Results. 80 % of children aged 6–7 years made mistakes while using Turbuhaler, 73.3 % — metered-dose inhaler, 60 % — Easyhaler. There were no mistakes in patients making inhalation by means of Diskhaler. 100 % of children aged 12–14 years incorrectly used metered-dose inhaler. Easyhaler was incorrectly used in 66.6 % of cases, Diskhaler — in 26.6 %. Among elder group, incidence of mistakes when making inhalations through Turbuhaler was lower — 40 % in 12–14-year-old group and 25 % — in 15–17-year-old (р < 0.05. Children of 15–17 years old are able to use Turbuhaler and Diskus (mistakes in 33.3 and 46.6 %, respectively. At the same time, none of the patients have done the correct inhalation by means of metered-dose inhaler, 93.3 % of the patients have mistakes when using Easyhaler. Conclusions. The incidence of mistakes depends on the age and inhaler type and reaches 26–100 %. Minimal quantity of mistakes is seen for Diskus (in all age groups, maxi­mal — for metered-dose inhaler. For the purpose of optimal inhaler choice in a child with bronchial asthma, it is advisable to measure the inspiratory flow with the help of In-Check-Dial before therapy administration.

Langsom by

DEFF Research Database (Denmark)

Jensen, Ole B.

2010-01-01

Dette kapitel vil foretage en kritisk diskussion af Citta Slow som byudviklingskoncept og forsøge at forholde sig til de bagvedliggende forestillinger og værdier. Særligt gøres dette med henblik på mobilitet som gennemgående tema. Kapitlet indeholder også en kort diskussion af den aktuelle diskus...

Comparative cost-effectiveness of a fluticasone-propionate/salmeterol combination versus anticholinergics as initial maintenance therapy for chronic obstructive pulmonary disease

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An

2010-12-01

Full Text Available Anand A Dalal1, Melissa H Roberts2, Hans V Petersen2, Christopher M Blanchette3, Douglas W Mapel41US Health Outcomes, GlaxoSmithKline, Research Triangle Park, NC; 2Division of Clinical and Outcomes Research, Lovelace Respiratory Research Institute, Albuquerque, NM; 3Kannapolis, North Carolina; 4Lovelace Clinic Foundation, Albuquerque, NM, USAPurpose: Relative costs and utilization-related outcomes of a fluticasone propionate 250 µg + salmeterol 50 µg combination (FSC, tiotropium bromide, and ipratropium as initial maintenance therapy in COPD have not been compared in a commercially-insured population.Methods: This retrospective, observational cohort study used health care claims data from January 2004 to June 2009 from a large administrative database for patients aged ≥40 years with COPD. Time-to-first COPD-related health care event beginning 30 days following therapy initiation with FSC (n = 16,684, ipratropium alone or in fixed dose combination with albuterol (n = 14,449, or tiotropium (n = 12,659 was estimated using Cox proportional hazard models that controlled for differences in patient demographic characteristics, health care utilization, and comorbidities at baseline. Mean adjusted costs and numbers of COPD-related health care encounters and prescription medication fills were compared among patients with 12 months of follow-up (FSC, n = 12,595; ipratropium, n = 10,617; tiotropium, n = 9126.Results: With FSC as the reference, risk for a COPD-related hospitalization and/or emergency department visit was significantly higher for ipratropium (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.50–1.79 and tiotropium (HR 1.29, CI 1.17–1.41. Mean adjusted 12-month COPD-related total health care costs were lower for FSC ($2068, standard deviation [SD] $1190 than for ipratropium ($2841, SD $1858 and tiotropium ($2408, SD $1511, both P < 0.05. Mean number of COPD-related hospitalizations, emergency department visits, and outpatient

Long acting β2 agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials

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Mensinkai Shaila

2004-08-01

Full Text Available Abstract Background The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD. We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. Methods After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1 ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC ≤ 88% of predicted, and Results Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2 and four were low quality (≤ 2. The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported. Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040. Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement, six reported less rescue inhaler usage (one reported no difference and five reported improved dyspnea scores (two reported no improvement. Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported. Conclusion In terms of clinical outcomes and safety, we could not find

Efeito de curto prazo do tiotrópio nos portadores de DPOC em tratamento com β2-agonista Short-term effect of tiotropium in COPD patients being treated with a β2 agonist

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Frederico Leon Arrabal Fernandes

2010-04-01

Full Text Available OBJETIVO: Avaliar o impacto de curto prazo do uso de tiotrópio em pacientes com DPOC grave e muito grave com queixas de dispneia apesar do tratamento com outros broncodilatadores. MÉTODOS: Estudo prospectivo incluindo pacientes com DPOC grave ou muito grave, com queixa de dispneia de pequenos esforços ou ao repouso. A cada 15 dias, o tratamento broncodilatador foi modificado: salmeterol, tiotrópio e associação salmeterol+tiotrópio. Ao final de cada regime, foram realizados testes de função pulmonar e teste de caminhada de seis minutos (TC6. Também foram avaliados o grau de dispneia e a capacidade de realização de atividades de vida diária. Para a avaliação das atividades de vida diária, foi utilizada a escala London Chest Activity of Daily Living (LCADL validado para uso no Brasil. RESULTADOS: Foram avaliados 52 pacientes. Desses, 30 completaram o estudo. A introdução de tiotrópio como monoterapia resultou em uma melhora significativa (p OBJECTIVE: To evaluate the short-term impact of tiotropium in patients with severe or very severe COPD who complain of dyspnea despite being currently treated with other bronchodilators. METHODS: A prospective study including patients with severe or very severe COPD and complaining of dyspnea at rest or on minimal exertion. Every 15 days, the bronchodilator treatment regimen was altered, from salmeterol to tiotropium to salmeterol+tiotropium. At the end of each regimen, pulmonary function tests and the six-minute walk test (6MWT were performed. The degree of dyspnea and the ability to perform activities of daily living were also assessed. To evaluate patient ability to perform activities of daily living, we employed the London Chest Activity of Daily Living (LCADL, validated for use in Brazil. RESULTS: We evaluated 52 patients, 30 of whom completed the study. The use of tiotropium in isolation resulted in significant improvement in dyspnea at baseline (mean Medical Research Council scale score

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

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Seidel Petra

2012-10-01

Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

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Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

2012-10-04

Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

β2-agonista de longa duração na doença pulmonar obstrutiva crônica (DPOC

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CAMPOS LUIZ EDUARDO MENDES

2000-01-01

Full Text Available No paciente com DPOC, os β2-agonistas de longa duração são capazes de produzir broncodilatação de intensidade semelhante à dos anticolinérgicos, mas, devido a sua propriedade lipofílica, a ação se prolonga por um período até 12 horas após a sua administração. Estudos comparativos entre salmeterol e formoterol sugerem eqüipotência entre 50mcg de salmeterol e 24 ou 12mcg de formoterol quando este é administrado respectivamente através do aerossol dosimetrado ou turbuhaler. É preciso considerar o tipo de inalador para se estabelecer a eqüipotência entre os dois agentes. Até mesmo pacientes com DPOC e cardiopatia associada podem fazer uso dos β2-agonistas de longa duração com segurança. O salmeterol, por ser agonista parcial, é mais seguro nesses casos de maior risco. A terapia broncodilatadora escalonada na DPOC pode ser revista. Brometo de tiotrópio é um novo anticolinérgico cuja ação pode se prolongar por mais de 1-3 dias e talvez seja o novo broncodilatador mais promissor na DPOC

Administrative claims analysis of asthma-related health care utilization for patients who received inhaled corticosteroids with either montelukast or salmeterol as combination therapy.

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Allen-Ramey, Felicia C; Bukstein, Don; Luskin, Allan; Sajjan, Shiva G; Markson, Leona E

2006-05-01

To compare asthma-related health care resource utilization among a matched cohort of asthma patients using inhaled corticosteroids (ICSs) plus either montelukast (MON) or salmeterol (SAL) as combination therapy for asthma, during a time prior to the availability of fixed-dose combinations of ICS/SAL. A retrospective analysis using the PHARMetrics patient-centric claims database was conducted for the period preceding the market introduction of combination fluticasone-SAL in September 2000. Patients had to meet the following criteria for inclusion in the study: they had to be between the ages of 4 and 55 years; they had to have been continuously enrolled for 2 years; they had to have initiated ICS/MON or ICS/SAL therapy between July 1, 1998, and June 30, 1999; and they had to have had either (a) a diagnosis of asthma (based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 493.xx) for 2 outpatient visits, 1 or more emergency department (ED) visits, or 1 or more hospitalizations within 1 year or (b) pharmacy claim records that contained a National Drug Code for an antiasthma medication (betaagonist, theophylline, ICS, cromolyn, or leukotriene) 2 or more times within 1 year. ICS/MON and ICS/SAL patients were matched 1 to 1 on age and propensity score. Outcomes included asthma-related hopitalizations and ED visits with ICD-9-CM codes of 493.xx, and oral corticosteroid (OCS) fills and short-acting beta-agonist (SABA) fills. Multivariate regression analyses were performed. Subgroup analyses based on sequential or concurrent initiation of combination therapy were also conducted. A total of 1,216 patients were matched (ICS/MON = 608; ICS/SAL= 608). Decreased odds of ED visits and/or hospitalizations were observed with ICS/MON (adjusted odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.35- 0.98) versus ICS/SAL. The odds of postindex OCS fills were not different for ICS/MON and ICS/SAL patients (adjusted OR = 1.04; 95

Modeling the impact of increased adherence to asthma therapy.

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Amory Schlender

Full Text Available BACKGROUND: Nonadherence to medications occurs in up to 70% of patients with asthma. The effect of improving adherence is not well quantified. We developed a mathematical model with which to assess the population-level effects of improving medication prescribing and adherence for asthma. METHODS: A mathematical model, calibrated to clinical trial data from the U.S. NHLBI-funded SOCS trial and validated using data from the NHLBI SLIC trial, was used to model the effects of increased prescribing and adherence to asthma controllers. The simulated population consisted of 4,930 individuals with asthma, derived from a sample the National Asthma Survey. Main outcomes were controller use, reliever use, unscheduled doctor visits, emergency department (ED visits, and hospitalizations. RESULTS: For the calibration, simulated outcomes agreed closely with SOCS trial outcomes, with treatment failure hazard ratios [95% confidence interval] of 0.92 [0.58-1.26], 0.97 [0.49-1.45], and 1.01 [0-1.87] for simulation vs. trial in the in placebo, salmeterol, and triamcinolone arms, respectively. For validation, simulated outcomes predicted mid- and end-point treatment failure rates, hazard ratios 1.21 [0.08-2.34] and 0.83 [0.60-1.07], respectively, for patients treated with salmeterol/triamcinolone during the first half of the SLIC study and salmeterol monotherapy during the second half. The model performed less well for patients treated with salmeterol/triamcinolone during the entire study duration, with mid- and end-point hazard ratios 0.83 [0.00-2.12] and 0.37 [0.10-0.65], respectively. Simulation of optimal adherence and prescribing indicated that closing adherence and prescription gaps could prevent as many as nine million unscheduled doctor visits, four million emergency department visits, and one million asthma-related hospitalizations each year in the U.S. CONCLUSIONS: Improvements in medication adherence and prescribing could have a substantial impact on

[Theoretical and practical assessment of Lille general practice and pharmacy students' knowledge about use of inhaler devices for asthma control].

Science.gov (United States)

Veylon, P; Rochoy, M; Gautier, S; Wallaert, B; Berkhout, C

2018-04-01

Asthma is a potentially serious chronic respiratory disease impacting patients quality of life. Satisfactory control requires proper use of inhaled devices. This study assesses general medical residents and pharmacy students knowledge about proper use of inhaled asthma devices. We evaluated knowledge of 43 general practice students and 43 pharmacy students in Lille for three inhaler devices (metered-dose inhaler, Turbuhaler ® and Diskus ® ) during individual interviews. Students were assessed on 8 proper use criterias for each device. General practice and pharmacy students are unfamiliar with proper use of inhaler devices. However, pharmacy students get better average scores than general practice students for all devices included in this study: 6.3/8 respected criterias against 5/8 for metered-dose inhaler; 5.3/8 against 3.2/8 for Turbuhaler ® ; and 6/8 against 4.3/8 for Diskus ® . Pharmacy students more frequently perform a demonstration of proper use to patients when a device is first prescribed or when a prescription is renewed; general practice students more frequently ask patients themselves to perform a demonstration of proper use. Introducing trainings workshops for inhaler devices to pharmacy and general practice students appears appropriate in order to promote therapeutic patient education, to increase asthma control and better patients life quality. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Estudo comparativo do manuseamento dos vários dispositivos de inalação utilizados em Portugal** Trabalho concotTente ao Premia Thome Villar/Boehringer Ingelhcim, 1999 (Secção A

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António Morais

2001-01-01

Full Text Available RESUMO: A terapêutica inalatória tern urn papel fundamental no tratamento das doençs respiratórias. Esta importância deve-se à administração directa do fármaco na area em tratamento, o que leva à necessidade de menores doses de farmaco, com menores efeitos secundários, um mais rápido início de acção e uma maior eficácia terapêutica do mesmo. Quando prescrevemos urn inalador, temos que ter em conta as varias caracteristicas quer do farmaco, quer do inalador, nomeadamente a facilidade com que este ultimo pode ser manuseado.O objectivo deste estudo foi o de pesquisar o grau de dificuldade exigido na realização da manobra inalat6ria dos vários inaladores existentes em Portugal, alem das preferencias em relação aos mesmos por parte da população estudada. Uma população de 80 individuos, com media de idades de 45 anos (24-78, sendo 49 (61,2% homens e 31 (38,8% mulhercs, sem anterior contacto com inaladores, apos a aprcsentação de 6 inaladores frequentementc utilizados em Portugal (MDI e os DPI's Rotahaler, Turbohaler, Diskus, Diskhaler e Aerolizer, escolhiam qual delcs eque achavam ser esteticamentc o mais c o menos atractivo. Seguidamente cram instruldos sobre a maneira correcta de inalar com os aparelhos de inalação incluidos no estudo. Apos a instrução de cada inalador, tinham 3 tentativas para inalar de forma correcta com o mcsmo. Após as manobras inalat6rias com os 6 inaladorcs, os individuos CSCOlhiam qual deles e que tinha sido o mais fáicil co mais difícil de manusear, e em caso de terem de efectuar terapêutica inalatória qual deles é que escolheriam é qual deles é que rejeitariam.O Disk us - 22 (27,5 % e o Aerolizer - 21 (26,2 % foram considerados os mais atractivos enquanto o Turbuhaler foi considcrado o menos atraente-18 (22,5 %. 0 Turbuhaler- 25 (31,2%, foi considerado como o mais facil de ser manuseado versus o MDI - 36

The association between glutathione S-transferase P1 ...

African Journals Online (AJOL)

Mahmoud I. Mahmoud

2011-08-10

Aug 10, 2011 ... B-adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care ... transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18(4):641–4.

Relief of dyspnoea by beta(2)-agonists after methacholine-induced bronchoconstriction

NARCIS (Netherlands)

van der Woude, HJ; Postma, DS; Politiek, MJ; Winter, TH; Aalbers, R

Virtually all asthma patients use bronchodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a

Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

NARCIS (Netherlands)

Broeders, M.E.A.C.; Molema, J.; Burnell, P.K.; Folgering, H.T.M.

2005-01-01

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles

Effects of two inhaled corticosteroid/long-acting beta-agonist combinations on small-airway dysfunction in mild asthmatics measured by impulse oscillometry

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Diong B

2013-08-01

Full Text Available Bill Diong,1 Kshitiz Singh,2 Rogelio Menendez31School of Engineering, Southern Polytechnic State University, Marietta, GA, USA; 2College of Science and Engineering, Texas Christian University, Fort Worth, TX, USA; 3Allergy and Asthma Research Center of El Paso, El Paso, TX, USABackground: We previously showed that the long-acting beta agonist (LABA salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS in 2- to 5-year-old children with reversible-airway disease within 15 minutes.Objective: We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5.Methods: Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol who had at least a 40% change in integrated low-frequency reactance postalbuterol were selected and randomized to receive either fluticasone propionate/salmeterol or budesonide/formoterol (15 subjects each. We collected three to six IOS replicates at baseline, at 5, 20, 40, 60, 120, and 240 minutes postdose at randomization, and after 4 weeks of twice-daily dosing. Blinded investigators calculated IOS frequency-dependent resistance and reactance (R5–R20 and AX, indicative of small-airway dysfunction, and also estimated the peripheral airway resistance (Rp and peripheral airway compliance (Cp, using a respiratory-impedance model.Results: At randomization visits, onset of action was detected as early as 5 minutes (t-test, P < 0.05 after fluticasone propionate/salmeterol by Cp, and within 5 minutes after budesonide/formoterol by R5–R20, AX, Rp, and Cp. However, after 4 weeks of dosing, only Rp was significantly different (from 60 to 120 minutes after fluticasone

Communication during pediatric asthma visits and child asthma medication device technique 1 month later.

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Sleath, Betsy; Carpenter, Delesha M; Ayala, Guadalupe X; Williams, Dennis; Davis, Stephanie; Tudor, Gail; Yeatts, Karin; Gillette, Chris

2012-11-01

This study investigated how provider demonstration of and assessment of child use of asthma medication devices and certain aspects of provider-patient communication during medical visits is associated with device technique 1 month later. Two hundred and ninety-six children aged 8-16 years with persistent asthma and their caregivers were recruited at five North Carolina pediatric practices. All of the medical visits were audio-tape recorded. Children were interviewed 1 month later and their device technique was observed and rated. If the provider asked the child to demonstrate metered dose inhaler technique during the medical visit, then the child was significantly more likely to perform a greater percentage of inhaler steps correctly 1 month later. Children with higher asthma management self-efficacy scores were significantly more likely to perform a greater percentage of diskus steps correctly. Additionally, children were significantly more likely to perform a greater percentage of diskus steps correctly if the provider discussed a written action plan during the visit. Children were significantly more likely to perform a greater percentage of turbuhaler steps correctly if they asked more medication questions. Providers should ask children to demonstrate their inhaler technique during medical visits so that they can educate children about proper technique and improve child asthma management self-efficacy. Providers should encourage children to ask questions about asthma medication devices during visits and they should discuss asthma action plans with families.

Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation

DEFF Research Database (Denmark)

Magnussen, Helgo; Watz, Henrik; Kirsten, Anne

2014-01-01

-controlled fashion, one group of patients continues to receive tiotropium, salmeterol and fluticasone, while the second group initiates stepwise withdrawal of fluticasone. The primary end point is time to first moderate or severe exacerbation following randomized treatment over 52 weeks. Lung function, symptoms...

Canadian Economic Evaluation of Budesonide-Formoterol as Maintenance and Reliever Treatment in Patients with Moderate to Severe Asthma

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Elizabeth Miller

2007-01-01

Full Text Available OBJECTIVES: To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents.

Combined inhalation of beta2 -agonists improves swim ergometer sprint performance but not high-intensity swim performance

DEFF Research Database (Denmark)

Kalsen, Anders; Hostrup, Morten; Bangsbo, Jens

2014-01-01

There is a high prevalence of asthma and airway hyperresponsiveness (AHR) in elite athletes, which leads to a major use of beta2 -agonists. In a randomized double-blinded crossover study, we investigated the effects of combined inhalation of beta2 -agonists (salbutamol, formoterol, and salmeterol...

Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study

DEFF Research Database (Denmark)

Celli, Bartolomé R; Thomas, Nicola E; Anderson, Julie A

2008-01-01

was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5-22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV(1) declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who...

Tiotropium in COPD: clinical outcomes and economic evidence

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Orietta Zaniolo

2010-03-01

Full Text Available Tiotropium bromide is a once-daily anticholinergic bronchodilator with duration of action of at least 24 hours. In clinical trials, tiotropium has been compared with placebo, ipratropium or salmeterol, the most frequently used long-acting β2 agonist. When compared with ipratropium or placebo in COPD management, tiotropium resulted associated with FEV1, dyspnoea and health-related quality of life (QoL improvement, along with reduced exacerbation and hospitalisation rates. In comparison to salmeterol, it proved to be superior in terms of lung function improvement and exacerbation risk reduction. Recently, the randomised, double-blind trial UPLIFT showed that 4 years of therapy with tiotropium were associated with improvements in lung function, QoL, and exacerbations, and with an effective reduction of mortality compared with control group in 5,993 patients with moderate to very-severe COPD. These encouraging clinical effects are to be traded against the pharmaceutical cost increase induced by the inclusion of tiotropium in routine care. However, published work indicates that this pharmaceutical cost increase may be totally or partially offset by the reduction in costs needed for exacerbations management and hospitalisations. Depending on the setting analysed, tiotropium is estimated to dominate ipratropium and salmeterol or to be associated with an incremental cost of less than € 2,500 per exacerbation avoided. An Italian model based on UPLIFT data shows that therapy including tiotropium induces an incremental cost of € 6,700 for year of life and of € 7,916 for Quality-adjusted Life Year gained, with respect to routine care alone. These values are much lower than commonly accepted thresholds and than cost/effectiveness results estimated for other long-acting bronchodilators. In conclusion, available evidence suggests that tiotropium may prove an appropriate therapeutic option with a largely affordable cost.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

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Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

2016-01-01

Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

OpenAIRE

Seidel Petra; Alkhouri Hatem; Lalor Daniel J; Burgess Janette K; Armour Carol L; Hughes J

2012-01-01

Abstract Background Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived ce...

Comparison of hospitalizations, emergency department visits, and costs in a historical cohort of Texas Medicaid patients with chronic obstructive pulmonary disease, by initial medication regimen.

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Rascati, Karen L; Akazawa, Manabu; Johnsrud, Michael; Stanford, Richard H; Blanchette, Christopher M

2007-06-01

Limited information is available on the relative outcomes and treatment costs of various pharmacotherapies for chronic obstructive pulmonary disease (COPD) in a Medicaid population. This study compared the effects of initial medication regimens for COPD on COPD-related and all-cause events (hospitalizations and/or emergency department [ED] visits) and COPD-related and all-cause costs. The study population was a historical cohort of Texas Medicaid beneficiaries aged 40 to 64 years with COPD-related medical costs (International Classification of Diseases, Ninth Revision, Clinical Modification codes 491.xx, 492.xx, 496.xx), 24 months of continuous Medicaid enrollment (12 months before and after the index prescription), and at least 1 prescription claim (index) for a combination product containing fluticasone propionate + salmeterol, an inhaled corticosteroid, salmeterol, or ipratropium between April 1, 2001, and March 31, 2003. The analyses of events employed Cox proportional hazards regression, controlling for baseline factors and preindex events. The analyses of costs used a 2-part model with logistic regression and generalized linear model to adjust for baseline characteristics and preindex utilization and costs. The study population included 6793 patients (1211 combination therapy, 968 inhaled corticosteroid, 401 salmeterol, and 4213 ipratropium). Only combination therapy was associated with a significantly lower risk for any COPD-related event (hazard ratio [HR] = 0.733; 95% CI, 0.650-0.826) and any all-cause event (HR = 0.906; 95% CI, 0.844-0.972) compared with ipratropium. COPD-related prescription costs were higher in all cohorts compared with the ipratropium cohort, but COPD-related medical costs were lower, offsetting the increase in prescription costs. For all-cause costs, prescription costs were higher in the combination-therapy cohort (+$415; P costs in the combination-therapy cohort (-$1735; P costs. In this historical population of Texas Medicaid

Treatment of bronchial asthma with low-level laser in attack-free period at children

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Ailioaie, C.; Ailioaie, Laura

2000-06-01

Bronchial asthma is a common disease in both the pediatric and adult populations, characterized by wide variations over short periods of time in resistance to airflow in intrapulmonary airways. A primary goal in the use of low- level laser therapy (LLLT) was the safe, effective and rapid palliation of symptoms owing to tracheal or bronchial obstruction. We have investigated the effects of LLLT comparatively with other modality trials in children's asthma. In the study were included 98 patients aged 10-18 years diagnosed with moderate or severe asthma, in attack- free period. The patients were divided into 3 groups. Group 1 received only laser therapy using extra meridian acupuncture points and scanning technique. Group 2 was treated only with inhaled Serevent 2 X 25 micrometers , two times daily, 3 months. Group 3 was tread with Theophylline retard in dosage of 15-mg/kg/12 h, 3 months. At the end of treatment we remarked a noticeable improvement of the clinical, functional and immunological characteristics at 83 percent of patients in group 1, comparatively with only 70 percent (group 2) and 53 percent (group 3). The LLLT had a very good action on bronchial patency , displayed an immunocorrecting action and is recommended in attack-free periods at children.

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

DEFF Research Database (Denmark)

Stempel, David A; Raphiou, Ibrahim H; Kral, Kenneth M

2016-01-01

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the ris...

Withdrawal of inhaled glucocorticoids and exacerbations of COPD

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Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

2014-01-01

fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

Long-acting beta(2)-agonists in management of childhood asthma

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Bisgaard, H

2000-01-01

This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

Radioactive metallic stent for the treatment of esophageal cancer in animal model and clinical trial

Energy Technology Data Exchange (ETDEWEB)

Park, K. B. [Korea Atomic Energy Research Institute, Taejeon (Korea); Lee, J. D. [Yonsei Univ., Seoul (Korea)

2000-03-01

The purpose of this study is to evaluate tissue response of self-expandable metallic stent covered Ho-166 in normal canine esophagus. Ho-166 was incorporated within polyurethan and covered over the outer surface of self-expandable metallic stents(diameter ; 18mm, length ; 40mm). Metallic stents with radioactivity of 4.0-7.8mCi (Group A), 1.0-1.8mCi (Group B) and 0.5-0.7mCi (Group C) were placed in normal mid-esophagus in twelve dogs (Group A), five (Group B) and another five dogs (Group C) respectively. Estimated radiation dose was 200-392Gy in Group A, 50-90Gy in Group B, and 25-35 Gy in Group C. The dogs were sacrified at two or three months later. In group A, mid-esophagus stricture, mucosal ulceration were found. Sereve fibrosis and degeneration of muscular propria, outer one half were found in three and complete fibrosis of esophageal wall in seven and fibrosis of esophageal wall and periesophageal soft tissue in two. In group B, glandular atrophy and submucosal fibrosis were found but muscular layer was intact. In group C, no histological change was demonstrated in three but submucosal inflammation and glandular atrophy with intact mucosa in two. Self-expandable metallic stent covered with Ho-166 may be used safely in esophagus without complication. 21 refs., 17 figs., 2 tabs. (Author)

Specifika současné ruské diskuse o Sovětském svazu

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Zdeněk Bělonožník

2014-06-01

Full Text Available The aim of the article is to introduce contemporary Russian discussion on the USSR and Russia in broader political and publicist context. Both positive and negative interpretations of the Russian/Soviet history will be presented. The text does not pretend to provide exhaustive list of the particular “schools” and “movements” nor does it offer historical dynamics or institutional background of the discussion. The author rather intends to single out certain basic schemes and arguments that circulate in the discussions, place them in broader frames and anticipate their potential political consequences. Particularly, the text concentrates on various versions of the patriotic thinking that has been receiving broad popularity in today Russia. As the author is convinced, due familiarity with the contemporary Russian debate may help to better understand Russian internal as well as foreign policy nowadays: as it becomes clear, rise of patriotism in academia, society and politics are inseparable phenomena. Secondly, some of the arguments promoted by the contemporary Russian authors may enrich Western (non-Russian sovietology and debate on socialist experiments as such. Last but not least, both content and form of the Russian academic discussion convincingly point at cultural conditionality of social and historical sciences. To some extent the discussion reminds perpetual Russian debate on national identity; cardinally new context in which it takes place however justifies attention paid to it.

Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

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van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

2014-01-01

Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

A systematic review of the cardiovascular risk of inhaled anticholinergics in patients with COPD

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Daniel E Hilleman

2009-06-01

Full Text Available Daniel E Hilleman,1 Mark A Malesker,1 Lee E Morrow,2 Dan Schuller21Department of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, USA; 2Division of Pulmonary and Critical Care Medicine, Creighton University School of Medicine, Omaha, Nebraska, USAAbstract: The long-term use of inhaled anticholinergic agents has recently been suggested to be associated with an excess risk of adverse cardiovascular (CV outcomes in patients with COPD. We identified 15 published studies that reported on the association between long-term inhaled anticholinergic use and adverse CV outcomes. Only 3 of the studies were adequately designed randomized controlled trials (RCTs. The first RCT that suggested that anticholinergic agents increased the risk of adverse CV outcomes was the Lung Health Study (LHS. Smokers randomized to inhaled ipratropium had a significantly increased risk of CV death than smokers receiving placebo. The LHS results have been questioned as the statistical tests used in the study were not adjusted for multiple tests and endpoints, a convincing dose-effect relationship between ipratropium use and the adverse CV outcomes was not established, and most of the CV deaths in the ipratropium group occurred in patients who were non-compliant to ipratropium. The Investigating New Standards for Prophylaxis in Reducing Exacerbations (INSPIRE was a RCT that compared the combination of salmeterol plus fluticasone against tiotropium in patients with COPD. All-cause mortality was significantly lower in the salmeterol plus fluticasone group (3% compared to the tiotropium group (6%. Fatal CV events occurred in 1% of the salmeterol plus fluticasone group compared to 3% in the tiotropium group. The INSPIRE trial was not designed to be a mortality trial, lacked adequate adjudication of fatal outcomes, and lacked a full intention-to-treat analysis of the data. The Understanding Potential Long-Term Impacts on Function

Mixing time effects on the dispersion performance of adhesive mixtures for inhalation.

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Floris Grasmeijer

Full Text Available This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de- agglomeration of the drug (and fine lactose particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables.

Mixing Time Effects on the Dispersion Performance of Adhesive Mixtures for Inhalation

Science.gov (United States)

Grasmeijer, Floris; Hagedoorn, Paul; Frijlink, Henderik W.; de Boer, H. Anne

2013-01-01

This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de-) agglomeration of the drug (and fine lactose) particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol) and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables. PMID:23844256

A asma e a DPOC na visão do pneumologista Asthma and COPD according to the pulmonologist

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Hisbello da Silva Campos

2009-04-01

Full Text Available OBJETIVO: Avaliar como o pneumologista vê o impacto da asma e da DPOC na sua clientela, e como ele vem tratando essas doenças. MÉTODOS: Inquérito com 227 pneumologistas participantes do VI Congresso de Asma e II Congressos Brasileiros de DPOC e de Tabagismo, realizados em 2007. RESULTADOS: As respostas dos pneumologistas mostraram que a DPOC é um problema de saúde pública igual ou maior que a asma, e que a DPOC causa inúmeros transtornos para o doente e para seus familiares. Na escolha do dispositivo inalatório, a simplicidade de uso é mais importante que o custo, havendo discreta predileção pelos sistemas Aeroliser® e Diskus®. A associação entre budesonida e formoterol foi a conduta terapêutica mais citada para o tratamento continuado do asmático sintomático, enquanto o brometo de tiotrópio foi o medicamento preferido pela maior parte para o tratamento continuado do portador de DPOC. A escolha do esquema para o tratamento continuado do asmático e do portador de DPOC é especialmente influenciada pela publicação de resultados de ensaios terapêuticos na literatura. CONCLUSÕES: A opinião do pneumologista sobre os temas abordados está de acordo com a literatura especializada.OBJECTIVE: To evaluate how pulmonologists view the impact that asthma and COPD has on their patients, as well as how they treat these diseases. METHODS: Survey including 227 pulmonologists participating in the VI Brazilian Asthma Conference, II Brazilian COPD Conference and II Brazilian Smoking Conference, all of which were held in 2007. RESULTS: According to the answers given by the pulmonologists, COPD is a public health problem of equal or greater importance than asthma, and COPD causes various disruptions in the lives of patients and their family members. When prescribing an inhalation device, pulmonologists feel that simplicity of use is more important than is the cost. There was a slight preference for the Aeroliser® and Diskus® systems. The

Long-acting β2-agonists in asthma

DEFF Research Database (Denmark)

Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten

2018-01-01

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without...... and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from...... mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue....

Evaluation of partial beta-adrenoceptor agonist activity.

Science.gov (United States)

Lipworth, B J; Grove, A

1997-01-01

A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

Analisi di costo efficacia nella terapia della BPCO

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Sergio Iannazzo

2005-12-01

Full Text Available Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV. OBJECTIVES: To analyze the economical and clinical impact of this recommendation, the affordability of its widespread application, as well as the relative pharmacoeconomical performance of the available options for severe and very severe COPD in Italy. METHODS: Published data on the Italian COPD population were fitted in a disease progression model based on a Markov chain representing severity stages and death. Alternative therapeutic options (salmeterol/ fluticasone - SF, formoterol/budesonide - FB, salmeterol alone - S, fluticasone alone - F and control - C were represented as competing arms in a decision tree. Efficacy data from international trials were expressed in terms of risk reduction. Clinical parameters used were number of exacerbations and symptom-free days. Direct and indirect costs were considered and valued according to present prices and tarifs. The analyses were conducted from National Health System, societal and patient perspectives with time horizons of 1,5, and 10 years, and lifelong. RESULTS: The yearly total direct costs of treating COPD patients in Italy is estimated in approximately 7 billion Euro, with a mean cost/patient/year around 2,400 Euro. Mean survival of the cohort is 11,5 years. The C and F strategies are dominated (i.e. are associated with worse outcomes and higher costs by all alternatives. S/F and F/B are the most effective strategies, with a slight clinical superiority of the latter, but are also marginally more expensive than S. Incremental cost/effectiveness of S/F vs. S is 679,55 Euro/avoided exacerbation and 3,31Euro/gained symptom-free day. CONCLUSIONS: The recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients, as compared with current

Hyperthyroidism complicating asthma treatment.

Science.gov (United States)

Zacharisen, M C; Fink, J N

2000-01-01

Asthma is one of the most common chronic medical conditions. The usual treatment includes quick relief bronchodilator medications of the sympathomimetic class and controller medications that may include the long-acting inhaled bronchodilator salmeterol. Mild adverse cardiac and central nervous system effects are common with these medications, requiring modifications in dose or occasionally switching to a different medication. Both asthma and thyroid disease are common disorders that occasionally occur together. Hyperthyroidism may exacerbate asthma. Many symptoms of hyperthyroidism are identical to the adverse effects of the commonly used inhaled bronchodilators and include tremor, nervousness, tachycardia, wide pulse pressure, palpitations, emotional lability, agitation, nightmares, aggressive behavior, and diarrhea. In this report we describe a patient with hyperthyroidism whose symptoms initially were thought to be adverse effects of the inhaled bronchodilator medications.

Injectable agents affecting subcutaneous fats.

Science.gov (United States)

Chen, David Lk; Cohen, Joel L; Green, Jeremy B

2015-09-01

Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

Hot topics from the Assemblies.

Science.gov (United States)

2015-03-01

INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD Authors: Rossi A, van der Molen T, Ricardo del Olmo, et al. Eur Respir J 2014; 44: 6, 1548-1556 SUMMARY: Inhaled corticosteroids (ICS) remain a highly controversial treatment for stable chronic obstructive pulmonary disease (COPD). Data linking high-dose ICS with complications, such as pneumonia and fractures, has necessitated a re-evaluation of their role in COPD management. Guidelines currently suggest ICS for patients with a forced expiratory volume in 1 s (FEV1) <50% predicted (or <60% in some regions) and a history of exacerbations. Nevertheless, it is well known that ICS and combination ICS/long-acting β-agonist (LABA) treatments are commonly used outside these groups. In view of the increasingly recognised dangers of ICS treatment, data demonstrating the safety of discontinuing ICS treatment is welcome.

Posílení postavení žen v rozvojovém světě: panelová diskuse

Czech Academy of Sciences Publication Activity Database

Formánková, Lenka

2008-01-01

Roč. 9, č. 2 (2008), s. 82-84 ISSN 1213-0028 R&D Projects: GA AV ČR 1QS700280503 Institutional research plan: CEZ:AV0Z70280505 Keywords : men and gender equality * feminization of poverty Subject RIV: AO - Sociology, Demography http://www.genderonline.cz

Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents

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Fabbri Leonardo M

2010-10-01

Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in

Tomáš Garrigue Masaryk v českých diskusích o literárním realismu

Czech Academy of Sciences Publication Activity Database

Hrdina, Martin

2014-01-01

Roč. 17, č. 1 (2014), s. 183-203 ISSN 1213-2144 R&D Projects: GA ČR GPP406/12/P839 Institutional support: RVO:68378068 Keywords : Masaryk, Tomáš Garrigue * Zola, Émile * literary realism * naturalism * empirical aesthetics Subject RIV: AJ - Letters, Mass-media, Audiovision

β2 agonists in athletes. An ergogenic aid? = β2 agonistas en deportistas. ¿Una ayuda ergogénica?

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Ospina Uribe, Carlos Fernando

2013-01-01

Full Text Available Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB. Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency, except salbutamol (maximum dose: 1.600 μg over 24 hours and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

Impact of different combinations of inhaled corticosteroids and long-acting sympathicomimetics on dental health of asthmatics.

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George Christoff

2012-07-01

Full Text Available The aim of the investigation is to study the effect of inhaled corticosteroids and long-acting sympathicomimetics on dental health in asthmatics. Thirty patients, from 20 to 55 years old, participate in the study. D-, M-, F- and DMFT indexes are determined in a 6 months period. All participants fill in a questionnaire. Asthmatics complain most frequently from oral dryness, take frequently sugar and soft drinks and visit irregularly dental practitioners. A significant increase in M-index is found out at the second visit. F-index increases considerably for patients treated with Beclometasone and Formoterol and D-index decreases significantly when treated with Budesonide and Formoterol. DMFT index increases considerably for all patients. Highest values of DMFT index are registered for patients treated with Fluticasone propionate and Salmeterol. Prolonged use of inhaled drugs with greater quantities of lactose leads to more impaired dental status in asthmatics and higher values of DMFT index.

February 2015 pulmonary case of the month: severe asthma

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Uppalapu S

2015-02-01

Full Text Available No abstract available. Article truncated at 150 words. History of present illness: A 50-year-old African-American woman with a history of asthma presented to the emergency department with a chief complaint of shortness of breath for 2 weeks. She reported some chest tightness, wheezing and dry cough. She denied fever, chills, myalgias or arthralgias at the time of admission. PMH, SH and FH: In addition to asthma, she has a past medical history of type 2 diabetes mellitus, hypertension, and multiple sclerosis. She admitted to social smoking but states she quit 6 to 7 months ago. She denies alcohol, recreational drug use, or a family history of early coronary artery disease, strokes or cancers. Medications: montelukast 10 mg daily; salmeterol/fluticasone 250/50 inhaled twice a day; albuterol inhaler as needed for shortness of breath; metformin 500 mg bid; dimethyl fumarate 240 mg bid; omega 3 fish oil; calcium carbonate 600 mg daily; naproxen 500 mg bid; lisinopril 10 mg daily ...

Acidity of unstimulated saliva and dental plaque in asthmatics, treated with inhaled corticosteroids and long-acting sympathicomimetics.

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Emilia Karova

2012-07-01

Full Text Available The number of asthmatics is continuously increasing all over the world. The aim of the study is to study the effect of different combinations of inhaled corticosteroids and long-acting sympathicomimetics on salivary and plaque pH in asthmatics with mild persistent asthma. The effect of different quantities of lactose, as gustatory corrector in the inhalers, is traced out.Thirty patients of both sexes, from 20 to 55 years old participated in the study. Salivary and plaque pH values are traced out in 30 minutes period after drug inhalation, at 6-months interval. It is found out that inhaled drugs cause significant decrease of initial salivary pH values, the lowest ones reported on first and fifth minute after the inhalation. The average salivary pH levels on the 30th minute remain significantly lower than initial ones.Most considerable changes in pH values are registered for patients treated with Fluticasone propionate and Salmeterol.

Moderní sport a problém ostatních Modern sport and the problem of others

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Kenji Ishigaki

2006-02-01

Full Text Available Otázka, kterou jsme chtěli v tomto příspěvku zkoumat, se týká způsobu, jakým se mezi atlety utváří soucit a společné porozumění. Naše diskuse o ostatních se neobrací k deontologickým problémům (např. měli bychom respektovat naše soupeře či technickým problémům (např. jak zajistit rovnost mezi atlety. Následující bod chceme předložit jako svůj závěr: "Základ sportovní etiky leží v tělesně založeném společenství s ostatními." The sports issue which we wanted to examine in this paper, by proposing the viewpoint of others, is the way in which sympathies and common understandings are established among athletes. Our discussion of others does not address deontological issues (we should respect our competitors, for instance or technical issues (how we ensure equality among athletes, for instance. We want to present the following point as our conclusion: "The foundation of sport ethics lies in body-based commonality with others."

Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle

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Shaikh N

2017-06-01

Full Text Available Nooreen Shaikh,1,2 Malcolm Johnson,3 David A Hall,4 Kian Fan Chung,1,2 John H Riley,3 Sally Worsley,5 Pankaj K Bhavsar1,2 1Experimental Studies, National Heart and Lung Institute, Imperial College London, 2Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, 3Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, 4Fibrosis and Lung Injury Development Planning Unit, GlaxoSmithKline, Stevenage, 5Respiratory Research & Development, GlaxoSmithKline, Uxbridge, UK Background: Intracellular mechanisms of action of umeclidinium (UMEC, a long-acting muscarinic receptor antagonist, and vilanterol (VI, a long-acting β2-adrenoceptor (β2R agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs. Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]. Cyclic adenosine monophosphate (cAMP was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2 messenger RNA using real-time quantitative polymerase chain reaction. Results: VI and salmeterol (10–12–10–6 M induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes attenuated VI-induced cAMP production (P<0.05, whereas pretreatment with UMEC (10–8 M, 1 hour restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus

HSP20 phosphorylation and airway smooth muscle relaxation

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Mariam Ba

2009-06-01

Full Text Available Mariam Ba1, Cherie A Singer1, Manoj Tyagi2, Colleen Brophy3, Josh E Baker4, Christine Cremo4, Andrew Halayko5, William T Gerthoffer21Department of Pharmacology, University of Nevada School of Medicine, Reno, NV, USA; 2Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA; 3Harrington Department of Biochemistry, Arizona State University, Tempe, AZ, USA; 4Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA; 5Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, MB, CanadaAbstract: HSP20 (HSPB6 is a small heat shock protein expressed in smooth muscles that is hypothesized to inhibit contraction when phosphorylated by cAMP-dependent protein kinase. To investigate this hypothesis in airway smooth muscle (ASM we showed that HSP20 was constitutively expressed as well as being inducible in cultured hASM cells by treatment with 1 µM isoproterenol or 10 µM salmeterol. In contrast, a mixture of proinflammatory mediators (interleukin-1β, tumor necrosis factor α, and interferon γ inhibited expression of HSP20 by about 50% in 48 hours. To determine whether phosphorylation of HSP20 is sufficient to induce relaxation, canine tracheal smooth muscle was treated with a cell permeant phosphopeptide that mimics the phosphorylation of HSP20. The HSP20 phosphopeptide antagonized carbacholinduced contraction by 60% with no change in myosin light chain phosphorylation. Recombinant full length HSP20 inhibited skeletal actin binding to smooth muscle myosin subfragment 1 (S1, and recombinant cell permeant TAT-HSP20 S16D mutant reduced F-actin filaments in cultured hASM cells. Carbachol stimulation of canine tracheal smooth muscle tissue caused redistribution of HSP20 from large macromolecular complexes (200–500 kDa to smaller complexes (<60 kDa. The results are consistent with HSP20 expression and macromolecular structure being dynamically regulated in airway

Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD

DEFF Research Database (Denmark)

Vestbo, Jørgen; Soriano, Joan B; Anderson, Julie A

2004-01-01

The prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing worldwide. Women may have greater susceptibility to COPD progression than men, and differences in efficacy and safety of respiratory medications by gender are largely unexplored. We aimed to determine whether...... the response to treatment in women with COPD differed from men in a large, 1-year double-blind trial ('TRISTAN'). In a sensitivity analysis, we compared 539 male and 180 female COPD patients, who were randomized to the saLmeterol/fluticasone combination 50/500mcg bid or placebo for 12 months. Combination...

Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

Science.gov (United States)

Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

2013-03-01

New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler.

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Holmes, Martin S; Seheult, Jansen N; O'Connell, Peter; D'Arcy, Shona; Ehrhardt, Carsten; Healy, Anne Marie; Costello, Richard W; Reilly, Richard B

2015-08-01

Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods. An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files. All exhalation factors had a statistically significant effect on drug delivery (pacoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%. Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.

Evaluation of pharmacotherapy of obstructive airway diseases in the Montenegrin outpatient care: comparison with two Scandinavian countries

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Duborija-Kovacevic Natasha

2012-06-01

Full Text Available Abstract Background This study is aimed at evaluating the pharmacotherapy of obstructive airway diseases (OAD in the Montenegrin outpatient care (MOC in 2010. Methods Data on the reimbursed drugs which were prescribed during the reference period were obtained from the National Database that was established within the Health Insurance Fund of Montenegro in 2004. We have applied the standard pharmacoepidemiologic methodology with the defined daily dose (DDD along with the Anatomical Therapeutic Chemical (ATC classification of drugs. Clinical entities of OAD were classified according to the International Classification of Diseases (ICD-Revision X. Results Prescribing and the subsequent use of drugs for OAD (ATC code R03 in 2010 was 18.18 DDD/1000inhabitants/day, much lower than in some developed countries. Fenoterol/ipratropium and salmeterol/fluticasone fixed combinations had the highest utilisation level, accounting for more than 50% of all OAD drugs. About 90% of OAD drugs were prescribed for COPD and asthma. Conclusions Obtained results indicate that there are still large differences in OAD drug utilisation in MOC when compared with developed countries, but also some improvement in pharmacological approach to the pharmacotherapy of OAD in comparison to the earlier period.

[Efficacy of regular or intermittent inhalation of corticosteroids in treatment of asthma and its effects on growth and development in children].

Science.gov (United States)

Li, Lin-Wei; Huang, Ying; Luo, Rong; Yan, Li; Li, Qu-Bei; Peng, Dong-Hong; Shu, Chang

2015-03-01

To observe the efficacy of regular or intermittent inhalation of salmeterol/fluticasone propionate (SM/FP) in the treatment of bronchial asthma and its effects on growth and development in children. A total of 112 children diagnosed with bronchial asthma between September 2012 and October 2013 were assigned to standardized treatment (standard group, n=56) and non-standardized treatment (intermittent group, n=56). Comparisons of clinical symptom scores and main pulmonary function indicators between the two groups were carried out before treatment and at 6 and 12 months after treatment. The growth velocity and changes in body mass index (BMI) were observed in the two groups. At 6 and 12 months after the treatment, the standard group had significantly reduced clinical symptom scores and significantly increased pulmonary function indicators (percentage of predicted peak expiratory flow, PEF%; percentage of forced expiratory volume in 1 second, FEV1%) (P0.05). Compared with intermittent inhalation, long-term regular inhalation of SM/FP performs better in controlling clinical symptoms and enhancing pulmonary function in children with asthma. Inhalation of SM/FP for one year reveals no apparent effect on the growth and development of these children.

Notes on testing equality and interval estimation in Poisson frequency data under a three-treatment three-period crossover trial.

Science.gov (United States)

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-01

When the frequency of event occurrences follows a Poisson distribution, we develop procedures for testing equality of treatments and interval estimators for the ratio of mean frequencies between treatments under a three-treatment three-period crossover design. Using Monte Carlo simulations, we evaluate the performance of these test procedures and interval estimators in various situations. We note that all test procedures developed here can perform well with respect to Type I error even when the number of patients per group is moderate. We further note that the two weighted-least-squares (WLS) test procedures derived here are generally preferable to the other two commonly used test procedures in the contingency table analysis. We also demonstrate that both interval estimators based on the WLS method and interval estimators based on Mantel-Haenszel (MH) approach can perform well, and are essentially of equal precision with respect to the average length. We use a double-blind randomized three-treatment three-period crossover trial comparing salbutamol and salmeterol with a placebo with respect to the number of exacerbations of asthma to illustrate the use of these test procedures and estimators. © The Author(s) 2014.

Přinese současná diskuse o rovnosti odměňování změny v Evropské legislativě?

Czech Academy of Sciences Publication Activity Database

Formánková, Lenka

2009-01-01

Roč. 10, č. 2 (2009), s. 74-76 ISSN 1213-0028 R&D Projects: GA ČR GA403/09/1839 Institutional research plan: CEZ:AV0Z70280505 Keywords : Gender pay gap * EU legislation * gender inequalities Subject RIV: AO - Sociology, Demography http://www. gender online.cz

Antonín Mandl – svědek diskusí mezi katolíky ve druhé polovině 60. let 20. století

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Vojtěch Novotný

2014-04-01

Full Text Available The general character of the memory of the contemporary witnesses and the fact that nearly no Christian samizdat of the 1960s has been preserved do not allow to offer a closer look to the topics discussed by the priests released from prison with their friends. We can only offer it through the witness of one of them, Antonín Mandl (1917–1972. His work from 1965 to 1967 is only a voice of an individual, but we can suppose that it echoes a broader debate, in which the experience of the earlier years has been confronted both with the contemporary form of the Czechoslovak society ruled by the Communist totalitarian regime and with the results of the Vatican Council II. The paper focuses on Mandl’s answer to the following three questions: In the relation to the Communism, is it proper to choose opposition, or collaboration? How should the priesthood in the contemporary society look like? What are the major axioms of Christian life, pastoral work and evangelisation?

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

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Vogelmeier CF

2018-04-01

Full Text Available Claus F Vogelmeier,1 Kenneth R Chapman,2 Marc Miravitlles,3 Nicolas Roche,4 Jørgen Vestbo,5 Chau Thach,6 Donald Banerji,6 Robert Fogel,6 Francesco Patalano,7 Petter Olsson,8 Konstantinos Kostikas,7 Jadwiga A Wedzicha9 1Member of the German Center for Lung Research (DZL, Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 2Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, ON, Canada; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Service de Pneumologie AP-HP, Cochin Hospital, University Paris Descartes (EA2511, Paris, France; 5Institute of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Novartis Sverige AB, Täby, Sweden; 9National Heart and Lung Institute, Imperial College London, London, UK Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY 110/50 µg with twice-daily salmeterol/fluticasone (SFC 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1 moderate/severe exacerbations according to prior exacerbation history and treatment, and 2 types of exacerbations according to health care resource utilization (HCRU during 1-year follow-up. Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75–0.93, ≥2 exacerbations (RR: 0.85, 95% CI: 0.70–1.03 and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74�

Effects of Salmeterol and Fluticasone Propionate Combination versus Fluticasone Propionate on Airway Function and Eosinophilic Inflammation in Mild Asthma

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Makoto Hoshino

2009-01-01

Conclusions: These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

Reklama v neziskovém sektoru: analýza recepce nekomerční reklamy v moderovaných skupinových diskusích

Czech Academy of Sciences Publication Activity Database

Kaderka, Petr

2006-01-01

Roč. 42, č. 2 (2006), s. 379-402 ISSN 0038-0288 R&D Projects: GA ČR(CZ) GD405/03/H053 Institutional research plan: CEZ:AV0Z90610518 Keywords : non-commercial advertising * focus group methodology * dialogue * Czech Subject RIV: AI - Linguistics Impact factor: 0.128, year: 2006

Development and validation of an UHPLC-MS/MS method for β2-agonists quantification in human urine and application to clinical samples.

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Bozzolino, Cristina; Leporati, Marta; Gani, Federica; Ferrero, Cinzia; Vincenti, Marco

2018-02-20

A fast analytical method for the simultaneous detection of 24 β 2 -agonists in human urine was developed and validated. The method covers the therapeutic drugs most commonly administered, but also potentially abused β 2 -agonists. The procedure is based on enzymatic deconjugation with β-glucuronidase followed by SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak resolution and rapid chromatographic separation, with reduced time and costs. The method was fully validated according ISO 17025:2005 principles. The following parameters were determined for each analyte: specificity, selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, matrix effect, recovery and carry-over. The method was tested on real samples obtained from patients subjected to clinical treatment under chronic or acute therapy with either formoterol, indacaterol, salbutamol, or salmeterol. The drugs were administered using pressurized metered dose inhalers. All β 2 -agonists administered to the patients were detected in the real samples. The method proved adequate to accurately measure the concentration of these analytes in the real samples. The observed analytical data are discussed with reference to the administered dose and the duration of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Single-inhaler combination therapy for maintenance and relief of asthma: a new strategy in disease management.

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Peters, Matthew

2009-01-01

When an adequate standard of asthma control is not achieved with maintenance treatment of inhaled corticosteroids, the addition of a long-acting beta(2)-adrenergic receptor agonist (LABA) bronchodilator is recommended. Using a combination product, salmeterol/fluticasone propionate (Seretide or Advair) or budesonide/formoterol (Symbicort) is preferred for convenience and avoids any risk that LABA might be used as monotherapy. As formoterol has a rapid onset of bronchodilator effect, the budesonide/formoterol combination can be used for both the maintenance and reliever components of asthma treatment (Symbicort SMART) and this is endorsed as an effective treatment by the Global Initiative for Asthma. The efficacy of this approach has been evaluated in a series of well conducted, controlled studies. Current control of asthma symptoms is improved or achieved with reduced total dose administration with Symbicort SMART compared with any reasonable alternate option. In every study, the risk of severe exacerbations was lower with Symbicort SMART than comparator treatment. Patients who benefit to the greatest extent are those with evidence of more severe asthma and greater exacerbation risk. When initiated in suitable patients in conjunction with appropriate education, Symbicort SMART is dominant in pharmacoeconomic terms. Symbicort SMART delivers improved asthma outcomes with lower treatment and social costs than any alternative.

CLINICAL AND ECONOMIC ANALYSIS OF THE LONG-TERM MAINTENANCE THERAPY BY COMBINED DRUGS OF BRONCHIAL ASTHMA IN SCHOOL CHILDREN, RESIDENTS OF THE RURAL REGIONS

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I.N. Ermakova

2011-01-01

Full Text Available The purpose of the study: selection of the supporting anti-asthma therapy (SAAT of the moderate asthma in school children, residents of the village with the lowest ratio of price and efficiency. The maximum frequency of achieving control of asthma was 64%. The spectrum of asthma medicines (drugs used in outpatient phase is represented. For 7 years, the proportion of the inhaled corticosteroid (ICS therapy in children with asthma has increased moderately by 5.5 times and was 66%, of which 2/3 was the combination of inhaled glucocorticosteroids. When using the combined drug salmeterol/fluticasone propionate (50/100 mkg during 3 months, after that fluticasone proionat during next 3 months as a level-controlled asthma the SAAT controlling BA increased 2 times. The cost of drugs accounted for 86% of direct medical costs (DMC, the cost of hospitalization decreased from 80 to 56% (DMC savings — 24%. The results of the analysis of «cost–effectiveness» SAAT allow to review the financial resources for health in favor of providing children with mild asthma inhaled high-performance combination that will improve the quality of medical care for children, residents of the rural regions.Key words: asthma, children, inhaled glucocorticosteriods, combined therapies, pharmacoeconomic analysis.

Impacto de las novedades terapéuticas para el tratamiento de la enfermedad pulmonar obstructiva crónica y el asma en atención primaria de Madrid, entre 1996 y 2005 Impact of new therapeutic products for the treatment of chronic obstructive pulmonary disease and asthma in primary care in Madrid between 1996 and 2005

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Cristina Rodríguez Escolar

2008-04-01

Full Text Available Objetivos: Analizar la tendencia de utilización de nuevos medicamentos para el tratamiento de las enfermedades obstructivas de las vías aéreas en atención primaria de Madrid entre 1996 y 2005, y evaluar su impacto en términos de oferta, consumo y costes. Métodos: Estudio de utilización de medicamentos de novedades terapéuticas del grupo R03 («medicamentos para enfermedades obstructivas de las vías aéreas» prescritos por médicos de atención primaria de Madrid, durante 1996 y 2005. Los datos de consumo y gasto a PVP provienen de la facturación de recetas. El consumo se expresa en dosis diarias definidas por 1.000 habitantes y día. Resultados: La oferta experimenta pocas variaciones cuantitativas aunque de gran interés cualitativo, al desaparecer fármacos sin utilidad terapéutica y comercializarse 6 novedades terapéuticas. En el año 2005, la utilización de estas últimas genera el 28,03% del total del consumo y el 79% de los costes. Las novedades de mayor impacto son salmeterol/fluticasona y tiotropio. Conclusiones: La oferta de medicamentos mejora cualitativamente al desaparecer los fármacos sin utilidad terapéutica. La prescripción de novedades terapéuticas tiene un gran impacto sobre el consumo total de los medicamentos del grupo R03 y, sobre todo, en los costes generados, dado su elevado su precio; sin embargo, aportan limitadas ventajas terapéuticas. Los nuevos medicamentos se han incorporado a gran velocidad a la prescripción.Objectives: To analyze the trend of use of new drugs for the treatment of chronic obstructive pulmonary disease in primary care of Madrid (Spain between 1996 and 2005, and to evaluate its impact in terms of supply, use and costs. Methods: Drug utilization study of new products of the R03 group (Anatomical Therapeutic Chemical Classificaction System: drugs for obstructive airway diseases prescribed by doctors of primary care of Madrid, during 1996 and 2005. Information on drug utilization and

Formoterol in the management of chronic obstructive pulmonary disease

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Paschalis Steiropoulos

2008-06-01

Full Text Available Paschalis Steiropoulos, Argyris Tzouvelekis, Demosthenes BourosDepartment of Pneumonology, University Hospital of Alexandroupolis, GreeceAbstract: Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD. There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β2-agonists, and long-acting β2-agonists such as formoterol. Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD. Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol. In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium. Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium. Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms. Formoterol has a favorable safety profile and is better tolerated than theophylline. Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD.Keywords: chronic obstructive pulmonary disease, formoterol, long-acting β2-agonists

Fluticasone furoate and vilanterol inhalation powder for the treatment of chronic obstructive pulmonary disease.

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Matera, Maria Gabriella; Capuano, Annalisa; Cazzola, Mario

2015-02-01

Fluticasone furoate/vilanterol (FF/VI) is a novel inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) fixed dose combination that, by simplifying the dosing schedule, allows, for the first time in a member of the ICS/LABA class, a shift from twice-daily to once-daily treatment. FF/VI is delivered via a novel, single-step activation, multi-dose dry powder inhaler for oral inhalation, Ellipta. Regrettably, there are no head-to-head trials that have shown superiority in the safety or efficacy of FF versus other ICSs, but evidence shows that VI has a quicker onset of effect versus salmeterol. However, the clinical utility of this effect in a maintenance medication is still questionable. Furthermore, benefits of FF/VI over twice-daily ICS/LABA comparator have not been shown yet and, in addition, its adverse event profile is generally consistent with the known class effects of an ICS/LABA fixed dose combination. In particular, there is an increase in the risk of pneumonia among patients treated with FF/VI relative to VI, mainly among those who benefit most from FF/VI. Nevertheless, the interesting pharmacological profiles of both FF and VI, the possibility that FF/VI can be administered once-daily, and the attractive characteristics of Ellipta are important features that could help FF/VI to be a successful combination in the treatment of chronic obstructive pulmonary disease.

Efficacy of perioperative administration of long-acting bronchodilator on postoperative pulmonary function and quality of life in lung cancer patients with chronic obstructive pulmonary disease. Preliminary results of a randomized control study

International Nuclear Information System (INIS)

Suzuki, Hidemi; Sekine, Yasuo; Yoshida, Shigetoshi; Suzuki, Makoto; Shibuya, Kiyoshi; Takiguchi, Yuichi; Tatsumi, Koichiro; Yoshino, Ichiro

2010-01-01

Long-acting bronchodilators are recommended as a first-line treatment for chronic obstructive pulmonary disease (COPD), although their effects for postoperative lung cancer patients with COPD are still not well known. A prospective randomized trial was used to examine the efficacy of bronchodilators on postoperative pulmonary function and quality of life (QOL). Twenty lung cancer patients with COPD who had lobectomies were randomized. A control group (n=10) did not receive bronchodilators. An experimental group (n=10) received tiotropium and salmeterol. Patients were divided into two COPD grades: stage I COPD and stage II-III COPD. Results for pulmonary function, 6-minute walking test, and the St. George's Respiratory Questionnaire (SGRQ) were compared. Diaphragmatic motion on dynamic magnetic resonance imaging was also analyzed. The patient demographics were similar in the two groups. Except for pulmonary function results at 2 weeks, no other parameters were significantly different. However, in stage II-III COPD, forced expiratory volume in 1 second, forced vital capacity, inspiratory capacity, the total score of the SGRQ, and diaphragmatic motion in the experimental group (n=5) were significantly better than those in the control group (n=4) at various time points (all P<0.05). The daily inhalation of bronchodilators was effective for maintaining the respiratory function and QOL in lung cancer patients with moderate to severe COPD. (author)

Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

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van den Berge Maarten

2012-06-01

Full Text Available Abstract Background Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD. We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. Methods In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF, and salbutamol use and assessed their course during exacerbations. Results There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively, whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. Conclusions Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.

Management of chronic obstructive pulmonary disease: moving beyond the asthma algorithm.

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Gordon, Erin; Lazarus, Stephen C

2009-11-01

For many years, chronic obstructive pulmonary disease (COPD) was considered a disease of fixed airflow obstruction for which there was no good treatment. Out of desperation and frustration, health care providers extrapolated from asthma to COPD, and standard asthma therapy was adopted without evidence for efficacy. In recent years, we have gained a better understanding of the pathophysiologic differences between asthma and COPD, and prospective controlled trials have provided a rationale for therapy. Smoking cessation is critically important, both as primary prevention and as an effective way to slow the decrease in lung function in patients with established disease. beta(2)-Adrenergic and anticholinergic agonists improve lung function and relieve symptoms in most patients. Tiotropium improves exercise tolerance and quality of life and reduces exacerbations and hospitalizations. The increase in lung function seen with tiotropium is sustained with continued use over at least 3 to 4 years. Inhaled corticosteroids decrease exacerbations and improve quality of life, and their effect seems greatest in patients with lower lung function and in exacerbation-prone patients. There is no evidence that inhaled corticosteroids alone affect mortality, despite the reduction in exacerbations and increased risk of pneumonia. In some patient populations, inhaled fluticasone, salmeterol, or the combination might slow the rate of loss of lung function. Rather than reflexively using effective asthma therapy in the patient with COPD, current and future therapy for COPD is increasingly evidence based and targeted to specific inflammatory pathways that are important in patients with COPD.

Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

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Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

2017-01-01

Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r 2 values ranged between 0.46 and 0.90 and the secondary OA increased the r 2  values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r 2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Pitfalls associated with the therapeutic reference pricing practice of asthma medication.

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Kalo, Zoltan; Abonyi-Toth, Zsolt; Bartfai, Zoltan; Voko, Zoltan

2012-07-20

Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our

SERUM LEVEL OF LIPIDS, APOLIPOPROTEINS AND VITAMIN D IN CHILDREN AT HIGH RISK OF CORONARY ARTERY DISEASE

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M BASHTAM

2002-06-01

of total and LOL cholesterol, triglyceride and APO B100 in boys are higher than girls are. Instantly in girls, mean ApoA1 and HDL cholesterol are higher than boys are. In addition, in neither case nor control group"s vitamin D showed significat relationship with total, LDL and HDL cholesterol and triglyceride (P > 0.05. Discussion. Generally, as optimum level of vitamin D is regulated by sereval environmental, genetic and metabolic factors, it is necessary to clear the real role of antioxidant vitamin Dfor decreasing CAD occurence especially in Iran.

Where current pharmacological therapies fall short in COPD: symptom control is not enough

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N. Roche

2007-09-01

Full Text Available Chronic obstructive pulmonary disease (COPD is a common and progressive condition that is currently the fourth leading cause of death worldwide. There is now a large body of evidence indicating that both pulmonary and systemic inflammation are present in patients with stable COPD and may underlie both respiratory symptoms and common comorbidities of this disease. Smoking cessation and long-term oxygen therapy have been shown to change the course of COPD and recent results obtained with the combination of fluticasone and salmeterol have indicated that it could decrease mortality and slow the decline in lung function in patients with this disease. However, some pharmacological treatments can significantly improve dyspnoea, exercise tolerance, limitations in activity, rate of exacerbations and quality of life (e.g. long-acting bronchodilators and inhaled corticosteroids combined with a long-acting beta2-agonist. The ability of these agents to modify the rate of disease progression remains to be firmly established in large-scale, long-term trials. The concept of disease modification itself in COPD may need to be revisited and more precisely defined in terms of markers and clinical outcomes, including extrarespiratory manifestations: agents that durably affect symptoms, activities, exacerbations and quality of life should probably be considered as disease modifiers. It is also reasonable to suggest that early diagnosis and treatment of patients with COPD might be the first and potentially most important disease-modifying intervention. There is clearly a need for new therapies that directly target the specific inflammatory processes underlying chronic obstructive pulmonary disease and its pulmonary and extrapulmonary manifestations.

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease.

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Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel Fm; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter Ma

2016-01-01

The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland-Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of -0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis.

An analysis of the utilisation and expenditure of medicines dispensed for the management of severe asthma.

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McGowan, B

2009-03-01

There are approximately 6,300 people in Ireland with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and with a fast growing elderly population the incidence of COPD is likely to increase. This study examines the prescribing patterns of medicines dispensed for the management Asthma\\/COPD in patients over the age of 35 years using the HSE-Primary Care Reimbursement Services (PCRS) prescribing databases. The HSE-PCRS pharmacy claims data, which covers all those over 70 years of age and means tested for those less than 70 years, was analysed for the years 2005\\/2006. Approximately 26,548 (17.9%) of patients who were prescribed a respiratory drug received inhaled short-acting beta2 agonists in combination with a regular standard-dose inhaled corticosteroid. A further 5,044 (3.4%) were also prescribed a regular inhaled long-acting beta2 agonist (salmeterol or formoterol). A total of 2506 patients (6.2%) on combination therapy were co-prescribed four different anti-asthmatic treatments inclusive of oral prednisolone. A small proportion of the patients prescribed a respiratory drug were co-prescribed nicotine replacement therapy (n = 5177, 3.5%). In total there were 9,728 (6.2%) patients prescribed a mucolytic drug in combination with a respiratory drug and the rate of co-prescribing with antibiotics was 22%. COPD is a debilitating disease that is primarily caused by smoking and is therefore largely preventable. The HSE-PCRS pharmacy claims data is a valuable tool for helping to assess the burden of this disease in the Irish context.

A designated centre for people with disabilities operated by St Aidan's Day Care Centre Limited, Wexford

LENUS (Irish Health Repository)

McGowan, B

2009-03-01

There are approximately 6,300 people in Ireland with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and with a fast growing elderly population the incidence of COPD is likely to increase. This study examines the prescribing patterns of medicines dispensed for the management Asthma\\/COPD in patients over the age of 35 years using the HSE-Primary Care Reimbursement Services (PCRS) prescribing databases. The HSE-PCRS pharmacy claims data, which covers all those over 70 years of age and means tested for those less than 70 years, was analysed for the years 2005\\/2006. Approximately 26,548 (17.9%) of patients who were prescribed a respiratory drug received inhaled short-acting beta2 agonists in combination with a regular standard-dose inhaled corticosteroid. A further 5,044 (3.4%) were also prescribed a regular inhaled long-acting beta2 agonist (salmeterol or formoterol). A total of 2506 patients (6.2%) on combination therapy were co-prescribed four different anti-asthmatic treatments inclusive of oral prednisolone. A small proportion of the patients prescribed a respiratory drug were co-prescribed nicotine replacement therapy (n = 5177, 3.5%). In total there were 9,728 (6.2%) patients prescribed a mucolytic drug in combination with a respiratory drug and the rate of co-prescribing with antibiotics was 22%. COPD is a debilitating disease that is primarily caused by smoking and is therefore largely preventable. The HSE-PCRS pharmacy claims data is a valuable tool for helping to assess the burden of this disease in the Irish context.

The influence of secondary processing on the structural relaxation dynamics of fluticasone propionate.

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Depasquale, Roberto; Lee, Sau L; Saluja, Bhawana; Shur, Jagdeep; Price, Robert

2015-06-01

This study investigated the structural relaxation of micronized fluticasone propionate (FP) under different lagering conditions and its influence on aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25°C, 75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60°C, 44% RH) for 14 days. Physicochemical, surface interfacial properties via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of the FP samples were characterized. Particle size, surface area, and rugosity suggested minimal morphological changes of the lagered FP samples, with the exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo surface reconstruction with a reduction in surface rugosity. LH and HH lagering reduced the levels of amorphous content over 90-day exposure, which influenced the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB analysis suggested that LH and HH lagering led to different interfacial interactions with lactose monohydrate but an increasing adhesive affinity with SX. HT lagering led to no detectable levels of the amorphous disorder, resulting in an increase in the adhesive interaction with lactose monohydrate. APSD analysis suggested that the fine particle mass of FP and SX was affected by the lagering of the FP. In conclusion, environmental conditions during the lagering of FP may have a profound effect on physicochemical and interfacial properties as well as product performance of binary and tertiary carrier-based DPI formulations.

K oprávnění svědka odepřít výpověď podle Ô 100 odstavec 2 trestního řádu [diskuse

Czech Academy of Sciences Publication Activity Database

Pipek, Jiří

2002-01-01

Roč. 49, č. 2 (2002), s. 40-45 ISSN 1210-6348 Institutional research plan: CEZ:AV0Z7068917 Keywords : testimony * refusal of testimony * Criminal Procedure : discussion Subject RIV: AG - Legal Sciences

Combination Therapy for Airflow Limitation In COPD

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Jafar Aslani

2012-08-01

Full Text Available Background and the purpose of the study Existing evidence confirms that no pharmacologic agent ameliorates the decline in the lung function or changes the prognosis of chronic obstructive pulmonary disease (COPD. We tried a critical combination therapy for management of COPD. Methods Current or past smoker (passive or active COPD patients with moderate to severe COPD who did not respond to primitive therapy (i.e., oral prednisolone (50 mg in the morning for 5 days; with Beclomethasone Fort (3 puff q12h, totally 1500 micrograms/day, Salmeterol (2 puffs q12h, 50 micrograms/puff and ipratropium bromide (4 puffs q8h for two months, enrolled to study. Furthermore they were received N-Acetylcysteine (1200 mg/daily, Azithromycin (tablet 250 mg/every other day and Theophylline (100 mg BD.Results The study group consisted of 44 men and 4 women, with a mean age and standard deviation of 63.6+/-12.7 years (range 22-86 years. Thirteen of 48 patients (27.0% was responder based on 15% increasing in FEV 1 (27.7+/-7.9 after 6.7+/-6.1 months (57.9+/-12.9 year old. There were statistically significant differences in age and smoking between responders and nonresponders (P value was 0.05 and 0.04 respectively. There was no difference in emphysema and air trapping between two groups (p=0.13. Conclusion Interestingly considerable proportion of patients with COPD can be reversible using combination drug therapy and patients will greatly benefit from different and synergic action of the drugs. The treatment was more effective in younger patients who smoke less.

Childhood asthma clusters and response to therapy in clinical trials.

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Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

2014-02-01

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Doping and respiratory system.

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Casali, L; Pinchi, G; Puxeddu, E

2007-03-01

Historically many different drugs have been used to enhance sporting performances. The magic elixir is still elusive and the drugs are still used despite the heavy adverse effects. The respiratory system is regularly involved in this research probably because of its central location in the body with several connections to the cardiovascular system. Moreover people are aware that O2 consumption and its delivery to mitochondria firstly depend on ventilation and on the respiratory exchanges. The second step consists in the tendency to increase V'O2 max and to prolong its availability with the aim of improving the endurance time and to relieve the fatigue. Many methods and substances had been used in order to gain an artificial success. Additional oxygen, autologous and homologous transfusion and erythropoietin, mainly the synthetic type, have been administered with the aim of increasing the amount of oxygen being delivered to the tissues. Some compounds like stimulants and caffeine are endowed of excitatory activity on the CNS and stimulate pulmonary ventilation. They did not prove to have any real activity in supporting the athletic performances. Beta-adrenergic drugs, particularly clenbuterol, when administered orally or parenterally develop a clear illicit activity on the myosin fibres and on the muscles as a whole. Salbutamol, terbutaline, salmeterol and formoterol are legally admitted when administrated by MDI in the treatment of asthma. The prevalence of asthma and bronchial hyperactivity is higher in athletes than amongst the general population. This implies that clear rules must be provided to set a correct diagnosis of asthma in the athletes and a correct therapy to align with the actual guidelines according to the same rights of the "other" asthmatic patients.

Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use.

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Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M; Huang, Jidong; Miller, Kay; Emery, Sherry L; Alexander, G Caleb

2015-07-01

The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Four Food and Drug Administration-approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.04), but there was no relationship with hospitalizations or outpatient encounters. Among this population, DTCA was associated with higher prescription sales and asthma-related emergency department use.

Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

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Nicolini Gabriele

2011-07-01

Full Text Available Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS and long acting beta-agonists (LABA. Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7% received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F pressurized metered dose inhaler (pMDI, 25 (22.5% fluticasone-salmeterol (FP/S dry powder inhaler (DPI, and 33 (29.7% budesonide-formoterol (BUD/F DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.

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Kaur, Manminder; Holden, Neil S; Wilson, Sylvia M; Sukkar, Maria B; Chung, Kian Fan; Barnes, Peter J; Newton, Robert; Giembycz, Mark A

2008-09-01

In diseases such as asthma, airway smooth muscle (ASM) cells play a synthetic role by secreting inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, or IL-8 and by expressing surface adhesion molecules, including ICAM-1. In the present study, PGE(2), forskolin, and short-acting (salbutamol) and long-acting (salmeterol and formoterol) beta(2)-adrenoceptor agonists reduced the expression of ICAM-1 and the release of GM-CSF evoked by IL-1beta in ASM cells. IL-1beta-induced IL-8 release was also repressed by PGE(2) and forskolin, whereas the beta(2)-adrenoceptor agonists were ineffective. In each case, repression of these inflammatory indexes was prevented by adenoviral overexpression of PKIalpha, a highly selective PKA inhibitor. These data indicate a PKA-dependent mechanism of repression and suggest that agents that elevate intracellular cAMP, and thereby activate PKA, may have a widespread anti-inflammatory effect in ASM cells. Since ICAM-1 and GM-CSF are highly NF-kappaB-dependent genes, we used an adenoviral-delivered NF-kappaB-dependent luciferase reporter to examine the effects of forskolin and the beta(2)-adrenoceptor agonists on NF-kappaB activation. There was no effect on luciferase activity measured in the presence of forskolin or beta(2)-adrenoceptor agonists. This finding is consistent with the observation that IL-1beta-induced expression of IL-6, a known NF-kappaB-dependent gene in ASM, was also unaffected by beta(2)-adrenoceptor agonists, forskolin, PGE(2), 8-bromo-cAMP, or rolipram. Collectively, these results indicate that repression of IL-1beta-induced ICAM-1 expression and GM-CSF release by cAMP-elevating agents, including beta(2)-adrenoceptor agonists, may not occur through a generic effect on NF-kappaB.

Indacaterol for chronic obstructive pulmonary disease: systematic review and meta-analysis.

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Vincent C H Chung

Full Text Available BACKGROUND: Inhaled bronchodilators are the first-line therapy for COPD. Indacaterol is a novel addition to existing long-acting bronchodilators. OBJECTIVES: Systematic review of randomized controlled trials (RCT ON efficacy and safety of indacaterol as compared: 1 with placebo at different dosages, 2 with existing bronchodilators; (3 as add-on treatment to tiotropium. METHODS: We searched 13 electronic databases, including MEDLINE, EMBASE and CENTRAL, and contacted the manufacturer for unpublished data. Primary outcome was mean FEV1 change at 12(th week, secondary outcomes included changes in SGRQ, TDI and BODE index at 6 months, exacerbation at 1 year, and worsening of symptoms. RESULTS: Twelve eligible RCTs of moderate risk of bias included data from 10,977 patients. Compared to placebo, indacaterol improved FEV1 by a weighted mean difference (WMD of 0.16 L (95%CI: 0.15, 0.18 L, p<0.001, homogeneously above the minimally important difference of 0.10 L. It offered clinically relevant improvement in all secondary outcomes except exacerbation. Magnitude of benefit did not differ significantly by dosage, but one treatment related death was reported at 300 ug. Efficacy of Indacaterol was similar to formoterol and salmeterol (FEV1 WMD = 0.04 L, 95%CI: 0.01 L, 0.07 L, p = 0.02; and tiotropium (FEV1 WMD = 0.01 L, 95%CI: -0.01, 0.03 L, p = 0.61. The use of indacaterol on top of tiotropium yielded additional improvement on FEV1 (WMD = 0.07 L, 95%CI: 0.05 L, 0.10 L, p<0.001. CONCLUSION: Indacaterol is safe and beneficial for patients with COPD at dosage ≤150 ug. It may serve as a good alternative to existing bronchodilators, or as an add-on to tiotropium for unresponsive patients. Use of higher dosage requires further justification.

Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use

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Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M.; Huang, Jidong; Miller, Kay; Emery, Sherry L.

2015-01-01

Rationale: The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. Objectives: To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. Methods: This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Measurements and Main Results: Four Food and Drug Administration–approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.04), but there was no relationship with hospitalizations or outpatient encounters. Conclusions: Among this population, DTCA was associated with higher prescription sales and asthma-related emergency

[Influence of education level on self-evaluation and control of patients with bronchial asthma].

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Zhao, Hai-jin; Cai, Shao-xi; Tong, Wan-cheng; Li, Wen-jun; Fu, Liang

2008-05-01

To investigate the effect of education on self-evaluation and control level in patients with bronchial asthma. Seventy-five asthmatic patients with the initial diagnosis in line with the American Thoracic Society criteria, including 46 with junior high school education or below (group A) and 29 with senior high school education or above (group B), were asked to complete a survey to assess their symptoms and asthma attacks. Asthma control test (ACT) and peak expiratory flow rate (PEFR) evaluation were performed 8, 12 and 24 weeks after salmeterol/fluticasone therapy. Step-down treatment was administered according to GINA guidelines. The self-evaluation of the patients was assessed according to ACT score, physical signs and pulmonary function. An ACT score over 19 indicate well controlled condition. The effect of education on the self-evaluation and control level of bronchial asthma was assessed. The two groups had similar basal level of pulmonary function (FEV1). Eight weeks after the therapy, 29 patients in group A had ACT score over 19, including 11 with high control level; in group B, 17 had ACT score over 19, of whom 4 showed high control level. There was no significant difference between the two groups in control levels and self-evaluation (P>0.05). At 12 weeks, 37 patients in group A had ACT score over 19, with 17 having high control level; 22 patients in group B had ACT score over 19, 4 showing high control level; the two groups were similar in the control levels (P>0.05) but showed significant difference in self-evaluation (Pevaluation (Peducation level may play a role in self-evaluation and control level of bronchial asthma, but its impact differs in the course of the treatment.

Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant

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Nawrocki-Raby Béatrice

2010-01-01

Full Text Available Abstract Background Staphylococcus aureus releases virulence factors (VF that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting β2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal combined with a corticosteroid (fluticasone propionate, FP was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. Methods A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. Results When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFα. Conclusions Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting β2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of β2 adrenergic receptor agonist and glucocorticoid.

Současná diskuse o sexuální výchově v České republice a stanovisko Římskokatolické církve k této problematice

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Procházková, Petra

2014-01-01

This work deals with sex education in the Czech Republic and Roma Catholic's concept of sex education. The first part is focused on concept of sexuality, the definition of sex education, its objectives, principles and methods in relation to the concept of education institutions and selected experts. It also includes a description of the historical context of the development of education. The second part is devoted to the Roman Catholic's view of human sexuality, sexual pedagogy, the role of p...

CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in guinea pigs.

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Sekioka, Tomohiko; Kadode, Michiaki; Yonetomi, Yasuo; Kamiya, Akihiro; Fujita, Manabu; Nabe, Takeshi; Kawabata, Kazuhito

2017-01-05

CysLT 1 receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT 2 receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT 2 receptor-mediated LTC 4 -induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC 4 is rapidly converted to LTD 4 by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor. In anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment, i.v. LTC 4 -induced bronchoconstriction was almost completely inhibited by montelukast, a CysLT 1 receptor antagonist, but not by BayCysLT 2 RA, a CysLT 2 receptor antagonist. The inhibitory effect of montelukast was diminished by treatment with S-hexyl GSH, whereas the effect of BayCysLT 2 RA was enhanced with increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung tissue isolated from LTC 4 -/S-hexyl-GSH-treated guinea pigs revealed air-trapping expansion, particularly at the alveolar site. Inhaled LTC 4 in conscious guinea pigs treated with S-hexyl GSH increased both airway resistance and airway hyperinflation. On the other hand, LTC 4 -induced air-trapping was only partially suppressed by treatment with the bronchodilator salmeterol. Although montelukast inhibition of LTC 4 -induced air-trapping was weak, treatment with BayCysLT 2 RA resulted in complete suppression of this air-trapping. Furthermore, BayCysLT 2 RA completely suppressed LTC 4 -induced airway vascular hyperpermeability. In conclusion, we found in this study that CysLT 2 receptors mediate LTC 4 -induced bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is therefore believed that CysLT 2 receptors contribute to asthmatic response involving air-trapping. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical utility and development of the fluticasone/formoterol combination formulation (Flutiform® for the treatment of asthma

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Tan RA

2014-09-01

Full Text Available Ricardo Antonio Tan,1 Jonathan Corren2 1California Allergy and Asthma Medical Group, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Pharmacologic treatment of asthma should be done with a stepwise approach recommended in treatment guidelines. If inhaled corticosteroids (ICSs alone are not adequate, ICSs in combination with long-acting β-agonists (LABAs are now established and widely used as the next step in effective controller therapy. Fixed-dose ICS/LABA combinations in a single device are the preferred form of delivery and improve compliance by enabling patients to get symptom relief from the LABA while receiving the anti-inflammatory benefits of ICSs. Fluticasone propionate/formoterol fumarate is one of the newest fixed-dose combinations. It has been in use in Europe in 2012, but is still under regulatory review in the US. Fluticasone is a synthetic ICS with potent anti-inflammatory effects, while formoterol is a selective β2-adrenergic receptor agonist with a rapid onset of bronchodilation within 5–10 minutes and a 12-hour duration of action. Fluticasone/formoterol has shown superior efficacy when compared to fluticasone or formoterol alone in multiple well-designed studies. The combination has shown comparable or “noninferior” benefits in lung function, clinical symptoms, and asthma control when compared with fluticasone and formoterol administered concurrently in separate inhalers. Fluticasone/formoterol provides similar efficacy with fluticasone/salmeterol, but with more rapid symptom relief. It has been compared directly with budesonide/formoterol with comparable results. Fluticasone/formoterol is well tolerated, with no unusual or increased safety concerns versus each individual component or other available ICS/LABA combinations. Fluticasone/formoterol is the latest entry into a relatively crowded market of branded fixed-dose preparations. Upcoming generic fixed-dose combinations and once-daily agents

Effect of β2-adrenergic receptor gene (ADRB2 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response

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Ambrose Helen J

2012-05-01

Full Text Available Abstract Background Evidence suggests that variation in the length of the poly-C repeat in the 3′ untranslated region (3′UTR of the β2-adrenergic receptor gene (ADRB2 may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3′UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response. Methods In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735, sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed. Results Poly-C repeat genotypes were assigned in 97% (2,192/2,250 of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients’ pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype. Conclusions The extensive sequence diversity present in the poly

ASM-024, a piperazinium compound, promotes the in vitro relaxation of β2-adrenoreceptor desensitized tracheas.

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Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-Adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024

Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety

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Cássio C. Ibiapina

2004-12-01

Full Text Available OBJETIVO: Rever a literatura sobre o hidrofluoralcano como propelente dos inaladores de dose medida contendo medicamentos empregados na asma. FONTES DOS DADOS: O levantamento bibliográfico foi realizado em bancos de dados eletrônicos - MEDLINE, MDConsult, HighWire, Medscape e LILACS - e por pesquisa direta - referentes aos últimos 15 anos -, utilizando-se as seguintes palavras-chaves: hidrofluoralcano, asma e infância. SÍNTESE DOS DADOS: Foram selecionados 43 artigos originais abordando a questão da substituição do clorofluorcarbono pelo hidrofluoralcano. Este gás mostrou-se como uma alternativa de propelente segura, com deposição pulmonar de 50 a 60% e eficácia significativa quando comparado com placebo (p OBJECTIVE: To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs. SOURCES OF DATA: Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out. SUMMARY OF THE FINDINGS: 43 original articles on the replacement of clorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < 0.003 in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers. CONCLUSIONS: Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced

Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

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Eva Wex

Full Text Available Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR, have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01. Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001. In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve

Magnetic resonance imaging (MRI) of the TMJ: Influence on therapy and inter-observer agreement of two radiologists; Magnetresonanztomographie (MRT) des Kiefergelenkes: Einfluss auf Therapieentscheidung und Uebereinstimmung zweier Auswerter

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Vahlensieck, M.; Okweschokwu, S. [Radiologie Haydnhaus, Bonn (Germany); Greven, M. [Medeco Zahnklinik, Bonn (Germany)

2002-11-01

Uebereinstimmungen wurden mittels kappa-Statistik geprueft. Ergebnisse: In 56% wurde eine Aenderung des Therapieplans nach MRT registriert. Eine messbare Konkordanz in der Auswertung fand sich fuer anteriore Diskusposition (kappa 0,44), transversale Diskusposition (kappa 0,46) und Kondylusstellung (0,45). Eine schlechte Konkordanz fand sich bei Signalveraenderungen des Diskus (kappa 0,14) und der bilaminaeren Zone (0,24), knoechernen Veraenderungen (0,13) und Zusatzbefinden (0,29). Diskussion: Die MRT des Kiefergelenkes hat einen messbaren Einfluss auf das therapeutische Vorgehen bei kraniomandibulaerer Dysfunktion (Internal Derangement). In der MRT-Beurteilung der Kriterien Diskusposition und Kondylusstellung kann von einer validen Reproduzierbarkeit ausgegangen werden. In der Beurteilung der Signalintensitaeten sowie knoecherner Veraenderungen ist mit einer deutlichen Untersucherabhaengigkeit zu rechnen. (orig.)

Patient perspectives on fluticasone–vilanterol versus other corticosteroid combination products for the treatment of asthma

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Bollmeier SG

2016-05-01

Full Text Available Suzanne G Bollmeier, Theresa R Prosser St Louis College of Pharmacy, St Louis, MO, USA Objective: Fluticasone furoate (FF, an inhaled corticosteroid (ICS, and vilanterol (VI, a long-acting beta2 receptor agonist (LABA, is a new combination used in an Ellipta® device. This article compares FF–VI to other ICS–LABA combinations available, particularly emphasizing product selection from the patient perspective. Data sources: A PubMED and EMBASE search completed in October 2015 identified trials using the MeSH terms “fluticasone”, “vilanterol”, and “asthma”. Additional information was gathered from references cited in the identified publications, the manufacturer, package insert, and ClinicalTrials.gov registry. Study selection/data extraction: Preference was given to randomized controlled clinical trials. Animal trials, trials for COPD, and non-English sources were excluded. Data synthesis: Seven efficacy trials of FF–VI in asthma were identified. Only one (24 weeks trial compared FF–VI to another ICS–LABA combination (fluticasone propionate–salmeterol. Primary outcomes (usually lung function and secondary outcomes (eg, quality of life and symptom scores were comparable. In three FF–VI safety trials, the type and frequency of common adverse reactions (ie, thrush and dysphonia were similar to those in clinical trials. Over 90% of subjects rated the Ellipta® device as “easy to use” and demonstrated correct device technique initially and at 4 weeks. Conclusion: Individuals may have drug- and device-specific preferences that should be incorporated into therapeutic decision making. Limited data indicate that clinical and patient-oriented efficacy/safety outcomes of FF–VI are likely comparable to other available combinations for adults with asthma. Patient-friendly features include once-daily dosing, flexibility of dose timing, and design/ease of the use of the device. Additional larger and long-term comparative

Bronchodilator treatment of stable COPD: long-acting anticholinergics

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W. Vincken

2005-09-01

Full Text Available Since airflow obstruction in chronic obstructive pulmonary disease (COPD is to some extent reversible, bronchodilators play an important role in the maintenance treatment of COPD the more they reduce hyperinflation and, as a result, improve dyspnoea and exercise capacity. Since parasympathetic activity is the dominant reversible component of airflow obstruction in COPD, inhaled short-acting anticholinergic agents (SAAC, in particular ipratropium, became an efficient and safe first-line treatment, especially when combined with a short-acting beta2-adrenergic receptor agonist. Even better results were obtained when combining the SAAC ipratropium to a long-acting beta2-adrenergic receptor agonist (LABA, once they became available. Recently, tiotropium bromide, the first of a new class of selective and long-acting anticholinergic agents was introduced for once-daily maintenance treatment of COPD patients. Several large long-term randomised clinical trials comparing tiotropium to placebo as well as to the SAAC ipratropium and the LABA salmeterol, have confirmed the long-acting and superior bronchodilator effect of tiotropium without any evidence of drug tolerance developing. These studies also have clearly demonstrated that tiotropium positively affects several other important health outcomes, such as dyspnoea sensation, exercise capacity, utilisation of rescue bronchodilators, health-related quality of life, COPD exacerbations and hospitalisations because of exacerbations. The improvement in these real-life outcomes appears related to the reduction in both static and dynamic hyperinflation. In all these studies, tiotropium was well tolerated and safe; the only relevant side-effect encountered being dry mouth, usually mild and often transitory. Finally, it has been shown that the combination of tiotropium with a LABA affords superior bronchodilatation than both agents alone, indicating that both classes of long-acting bronchodilators should be

[Efficacy on chronic obstructive pulmonary disease at stable stage treated with cutting method and western medication].

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Xu, Jian-hua; Xu, Bin; Deng, Yan-qing

2014-10-01

To compare the difference in clinical efficacy on chronic obstructive pulmonary disease (COPD) at stable stage in the patients among the combined therapy of cutting method and western medication (combined therapy), simple cutting method and simple western medication. One hundred and twenty cases of COPD were randomized into three groups, 40 cases in each one. In the cutting method group, for excessive phlegm pattern/syndrome, Feishu (BL 13), Danzhong (CV 17), Dingchuan (EX-B 1) and Yuji (LU 10) were selected as the main acupoints, and Lieque (LU 7) and Pianli (LI 6) were as the supplementary acupoints. For the pattern/syndrome of failure to consolidate kidney primary, Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4) and Yuji (LU 10) were selected as main acupoints, and Jueyinshu (BL 14) and Zusanli (ST 36) were as the supplementary acupoint. Three acupoints were selected alternatively in each treatment and the cutting method was applied once every 10 days. Three treatments made one session. Two sessions of treatment were required. In the western medication group, salbutamol sulfate aerosol, one press (200 μg/press) was used each night, as well as salmeterol xinafoate and fluticasone propionate powder for inhalation, one inhalation each night. The treatment of 1 month made one session. Two sessions were required. In the combined therapy group, the cutting method and western medication were applied in combination. The results of clinical symptom score, lung function test, arterial blood gas analysis, degree of inflation as well as clinical efficacy were observed before and after treatment in each group. Except the degree of lung inflation, the clinical symptom score, indices of lung function test, partial pressure of arterial blood gas (PaO2) and partial pressure of carbon dioxide (PaCO2) were all obviously improved after treatment as compared with those before treatment in each group (all Psyndrome differentiation and the combined therapy with western medication

Cost-effectiveness analysis of three different combinations of inhalers for severe and very severe chronic obstructive pulmonary disease patients at a tertiary care teaching hospital of South India.

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Altaf, Mohammed; Zubedi, Ayesha Mubeen; Nazneen, Fareesa; Kareemulla, Shaik; Ali, Syed Amir; Aleemuddin, N M; Hannan Hazari, Md Abdul

2015-01-01

This study aims at simplifying the practical patient management and offers some general indications for pharmacotherapeutic choice by the implementation of (Global Initiative for Chronic Lung Disease) guidelines. This study was designed to evaluate the clinical and economic consequences of salmeterol/fluticasone (SF), formoterol/budesonide (FB), and formoterol/fluticasone (FF) in severe and very severe chronic obstructive pulmonary disease (COPD) patients. The aim was to find out the most cost-effective drug combination between the three combinations (SF/FB/FF) in COPD patients. A prospective observational comparative study (cost-effectiveness analysis), in which 90 severe (30 ≤ forced expiratory volume in 1 s [FEV1] days (SFDs), number of moderate and severe exacerbations, Number of days of hospitalization and direct, indirect, and total cost to assess the cost-effectiveness of SF/FB/FF. Comparison of cost and effects was done during the period of 6 months of using SF/FB/FF. The average FEV1 for Group I, Group II, and Group III subjects at initial visit was 33.47%, 33.73%, and 33.20% and was increased to 36.60%, 35.8%, and 33.4%, respectively. A 3% increment in FEV1 was reported for Group I subjects (SF) and was highly significant statistically (t = -8.833, P = 0.000) at 95% CI. For Group II subjects (FB), a 2% increment in FEV1 was reported and was highly significant statistically (t = -9.001, P = 0.000) at 95% CI. For Group III (FF) subjects 0.2% increment in FEV1. The overall mean total cost for Group I, Group II, and Group III subjects during the 6 months period was found to be Rs. 29,725/-, Rs. 32,602/- and Rs. 37,155/-. Incremental cost-effectiveness of FB versus SF was Rs. 37,781/- per avoided exacerbation and Rs. 661/-per SFD. This study highlights the favorable therapeutic performance of combined inhaled bronchodilators and corticosteroids (SF/FB/FF), thus suggesting that healthcare costs would be also affected positively. Results from our study showed

The Normality of EU Sport Policy Studies: Disciplinary Locus in Political Science, Sport Science or Elsewhere?

Directory of Open Access Journals (Sweden)

Jacob Kornbeck

2014-05-01

Full Text Available The Normality of EU Sport Policy Studies: Disciplinary Locus in Political Science, Sport Science or Elsewhere? Mainstream European integration research has shown that research on the EU tends to follow the conjunctures of European integration itself. This realisation has led to some debate on which branch of political science – international relations or government – or indeed other academic disciplines is/are the most appropriate locus for such research. The paper takes these debates one step further by looking at the occurrence of ‘EU & sport’ studies within the wider field of EU studies. The main material used comes from the ECLAS database. Findings lead to a discussion of whether ‘EU & sport’ studies should rather be for EU specialists or for sport specialists and a plea for disciplinary normalisation whereby sport science would need to get more directly involved (without necessarily overwriting political science. Some ideas are added regarding the need for a mapping of Central & Eastern European scholarship. Normalita politických studií EU v oblasti sportu: místo v oborech politologie, sportovních vědách či jinde? Hlavní integrační proudy v evropském výzkumu dokumentují, že výzkum v EU má tendenci zkoumat evropskou integraci jako takovou. Toto poznání vedlo k diskusi, v kterém oboru politologie – mezinárodní vztahy či vláda – nebo i v jiných akademických disciplínách je nejvhodnější místo pro takový výzkum. Stať se pokouší posunout tyto diskuse o krok dále tím, že studie o „EU a sportu“ se posuzují v širším záběru EU studií. Hlavní informační zdroje pocházejí z databáze ECLAS. Naše zjištění vedou k diskusi o problematice „EU a sportu“ v tom smyslu, zda by tyto studie měly být spíše určeny odborníkům EU, nebo sportovním specialistům. Důležitá je otázka disciplinární začlenění této problematiky, s širším zapojením sportovních věd (aniž by

Cine MRI of the temporomandibular joint in comparison to static MRI and axiography; Cine-MRT des Kiefergelenks im Vergleich zur konventionellen MRT und Achsiographie

Energy Technology Data Exchange (ETDEWEB)

Beer, A.; Rummeny, E.J. [Inst. fuer Roentgendiagnostik der Technischen Univ. Muenchen, Klinikum rechts der Isar (Germany); Kolk, A.; Neff, A. [Klinik und Poliklinik fuer Mund-Kiefer-Gesichtschirurgie der Technischen Univ. Muenchen, Klinikum rechts der Isar (Germany); Hof, N. [Abt. fuer Diagnostische und Interventionelle Radiologie/Nuklearmedizin, Krankenhaus Dritter Orden, Muenchen-Nymphenburg (Germany); Treumann, T. [Roentgeninstitut, Kantonshospital Luzern (Switzerland)

2004-04-01

diskoligamentaeren Komplexes war in der Gruppe der funktionsgestoerten Gelenke die sMRT der cMRT ueberlegen (Sensitivitaet sMRT 85%, cMRT 76%), waehrend sich bei den Probanden kein signifikanter Unterschied zeigte (Sensitivitaet sMRT 97,4%, cMRT 98,3%). Die in der sMRT und cMRT ermittelten Funktionsdaten korrelierten signifikant untereinander sowie auch mit den entsprechenden achsiographischen Referenzwerten (r=0,90). In der sMRT stellte sich die durchschnittliche Diskus- und Kondylusmobilitaet 6% bzw. 10% hoeher als in der cMRT (p=0,001) bei leicht hoeherer Varianz (v=0,043 vs 0,38) dar. Die HKN-Werte stimmten in beiden MRT-Verfahren und mit der Achsiographie mit jeweils r=0,94 am besten ueberein. Schlussfolgerung: Die Cine-MRT ist in ihrer Genauigkeit mit der Achsiographie vergleichbar und stellt als dynamische Untersuchung eine wertvolle Ergaenzung zur konventionellen statischen MRT dar. (orig.)

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

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Rodriguez-Roisin R

2016-08-01

Full Text Available Roberto Rodriguez-Roisin,1 Kay Tetzlaff,2,3 Henrik Watz,4 Emiel FM Wouters,5 Bernd Disse,2 Helen Finnigan,6 Helgo Magnussen,4 Peter MA Calverley7 1Respiratory Institute, Servei de Pneumologia, Hospital Clínic IDIBAPS-CIBERES, Universitat de Barcelona, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 3Department of Sports Medicine, University of Tübingen, Tübingen, Germany; 4Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 5Department of Respiratory Medicine, University Hospital Maastricht, Maastricht University, Maastricht, the Netherlands; 6Department of Biostatistics and Data Sciences, Boehringer Ingelheim, Bracknell, UK; 7Institute of Ageing and Chronic Disease, Aintree University Hospital, Liverpool, UK Abstract: The WISDOM study (NCT00975195 reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume

Fluticasone-formoterol: a systematic review of its potential role in the treatment of asthma

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Prosser TR

2015-06-01

Full Text Available Theresa R Prosser, Suzanne G Bollmeier St Louis College of Pharmacy, St Louis, MO, USA Background: The purpose of this systematic review is to summarize and evaluate the available published data regarding the efficacy and safety of a combination product containing fluticasone propionate/formoterol (FP-F in order to establish its potential role compared with other inhaled combination corticosteroid/long-acting beta2 receptor agonists for the maintenance treatment of asthma.Methods: A PubMed and EMBASE search was conducted using the terms “fluticasone propionate”, “formoterol fumarate”, “Flutiform®”, and “asthma” in July 2014 to identify trials using this combination specifically for the treatment of asthma. Additional information was gathered from references cited in the identified publications, the package insert, and the ClinicalTrials.gov registry. All randomized controlled clinical trials for humans in asthma were evaluated for inclusion. Data from animal trials, clinical trials for chronic obstructive pulmonary disease, and non-English sources were excluded.Results: Seven short-term safety and efficacy trials of FP-F compared with its individual components and two comparison trials of FP-F versus other combination products were identified. Generally, the incidence of drug-related adverse events was low and consistent with previously reported drug class-related adverse events (ie, pharyngitis, dysphonia, and headache. The combination of FP-F was shown to be noninferior to fluticasone propionate/salmeterol for improving predose forced expiratory volume at one second (FEV1 and 2 hours post dose FEV1. FP-F was also noninferior to budesonide/formoterol in improving predose FEV1. Other clinical endpoints, including various symptom scores, asthma control, quality of life, and subjects’ assessment of the medications were not significantly different.Conclusion: Poor asthma control is common. The data from short-term studies

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

Science.gov (United States)

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

Leczenie skojarzone astmy wziewnymi glikokortykosteroidami i β2-agonistami

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Iwona Grzelewska-Rzymowska

2009-09-01

Full Text Available Dokonany w tym artykule przegląd badań ocenia dowody dotyczące leczenia astmy kombinacją wziewnych glikokortykosteroidów (wGKS i długo działających β2-agonistów (LAβA. Za leki pierwszego wyboru w astmie uznaje się wGKS. Integralną częścią leczenia astmy są β2-agoniści, najsilniejsze leki rozszerzające oskrzela. Obecnie dostępne są dwa leki z grupy długo działających β2-agonistów – formoterol i salmeterol. W kilku badaniach klinicznych udowodniono, że kombinacja wGKS i LAβA stanowi skuteczną i bezpieczną opcję w leczeniu astmy. Raporty GINA zalecają dodanie LAβA do małych i średnich dawek wGKS, co pozwala na uzyskanie kontroli astmy. Także z badań klinicznych uzyskaliśmy wiedzę, że kombinacja wGKS i LAβA daje większe korzyści w kontroli objawów astmy niż dwukrotnie większa dawka wGKS. Astma jest przewlekłą chorobą zapalną z rozwojem nadreaktywności oskrzeli. Przebieg kliniczny astmy jest zazwyczaj inny u różnych chorych, a nawet u tej samej osoby. W praktyce klinicznej choremu zaleca się podawanie stałych dawek wGKS, odpowiednich do stopnia ciężkości astmy, lub kombinacji wGKS i LAβA dwa razy dziennie i dodatkowo krótko działającego β2-agonisty „według potrzeby” (lub „na żądanie” dla złagodzenia objawów astmy. Ostatnio wprowadzono nowy model stosowania kombinacji wGKS i LAβA (budezonid/formoterol – tzw. SMART (Single Maintenance and Reliever Therapy. Jest to połączenie leków według koncepcji SMART stosowane zarówno w leczeniu przewlekłym dwa razy dziennie, jak i „według potrzeby” dla złagodzenia objawów bez dodatkowego stosowania leków tylko przynoszących ulgę. Badania kliniczne wykazały, że metoda SMART zmniejsza ryzyko ostrych zaostrzeń i jest dobrze tolerowana. Metoda ta ma korzystne działanie u pacjentów, u których utrzymują się objawy astmy pomimo leczenia kombinacją leków stosowanych tylko w leczeniu przewlekłym.

Cost-effectiveness analysis of a fixed-dose combination of indacaterol and glycopyrronium as maintenance treatment for COPD

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Chan M

2018-04-01

Full Text Available Ming-Cheng Chan,1,* Elise Chia-Hui Tan,2 Ming-Chin Yang3,* 1Section of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 2National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, Republic of China; 3Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Objective: The aim of this study was to evaluate the cost-effectiveness of the long-acting beta-2 agonist (LABA/long-acting muscarinic antagonist (LAMA dual bronchodilator indacaterol/glycopyrronium (IND/GLY as a maintenance treatment for COPD patients from the perspective of health care payer in Taiwan. Patients and methods: We adopted a patient-level simulation model, which included a cohort of COPD patients aged ≥40 years. The intervention used in the study was the treatment using IND/GLY, and comparators were tiotropium or salmeterol/fluticasone combination (SFC. Data related to the efficacy of drugs, incidence of exacerbation, and utility were obtained from clinical studies. Direct costs were estimated from claims data based on the severity of COPD. The cycle length was 6 months (to match forced expiratory volume in 1 second [FEV1] data, and the time horizons included 1, 3, 5, 10 years, and lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results. Costs were expressed in US dollars with a discount rate of 3.0%. Results: Compared to tiotropium and SFC, the incremental cost-effectiveness ratios (ICERs per quality-adjusted life year (QALY gained of patients treated with IND/GLY were US$5,987 and US$14,990, respectively. One-way sensitivity analysis revealed that the improvement in FEV1 provided by IND/GLY, the distribution of patients with regard to the severity of COPD, and acute exacerbation rate ratio were the key

Leczenie astmy wziewnymi glikokortykosteroidami i długo działającymi β2-agonistami – leczenie podtrzymujące i doraźne

Directory of Open Access Journals (Sweden)

Iwona Grzelewska-Rzymowska

2014-03-01

Full Text Available Autorzy przedstawiają niektóre problemy dotyczące wziewnego leczenia astmy kombinacją wziewnych glikokortykosteroidów (wGKS i długo działających β2-agonistów (LAβA, określanego jako leczenie podtrzymujące i doraźne (LPiD. Od 2006 roku międzynarodowe zalecenia dotyczące terapii astmy i jej zapobiegania (GINA – Globalna Inicjatywa dla Astmy rekomendują małe dawki wGKS jako pierwszą linię leczenia chorych na łagodną, przewlekłą astmę (drugi stopień leczenia i średnie dawki wGKS lub kombinację wGKS z LAβA jako preferowane leczenie astmy umiarkowanej (trzeci stopień leczenia. Wziewne glikokortykosteroidy stanowią główne leki w astmie, ponieważ są skuteczne w kontrolowaniu objawów choroby i wskaźników spirometrycznych. Salmeterol i formoterol (LAβA wywierają przede wszystkim działanie rozszerzające oskrzela, które utrzymuje się ponad 12 godzin. Ta grupa leków jest bardzo ważna w leczeniu astmy, pozwala bowiem na zmniejszenie dawki wGKS. Fundamentalną cechą astmy jest zapalenie, które dotyczy dużych i małych dróg oddechowych (o średnicy mniejszej niż 2 mm. Zajęcie małych oskrzeli jest powiązane z ciężkością choroby. W badaniach epidemiologicznych wykazano, że astma nie jest dostatecznie kontrolowana nie tylko w badaniach klinicznych, ale również w real-life. Nowy model terapii astmy, wykorzystujący budezonid oraz formoterol, określony jako leczenie podtrzymujące i doraźne, okazał się skuteczny i dobrze tolerowany. Poprawiał podatność pacjentów na terapię, zmniejszał ryzyko jej przerwania i poprawiał kliniczny przebieg astmy. Technologia Modulate pozwoliła na zmniejszenie cząstek dwupropionianu beklometazonu i formoterolu (BDP/F w połączeniu, co umożliwiło uzyskanie homogennego rozkładu cząstek leku w całym drzewie oskrzelowym. Ostatnio ta superdrobnocząstkowa formulacja BDP/F była oceniana u chorych na astmę według modelu LPiD. Wykazano, że leczenie kombinacj

Examining 30-day COPD readmissions through the emergency department

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Rezaee ME

2017-12-01

Full Text Available Michael E Rezaee,1 Charlotte E Ward,2,3 Bonita Nuanez,1 Daniel A Rezaee,4 Jeffrey Ditkoff,1,5 Alexandra Halalau1,6 1Oakland University William Beaumont School of Medicine, Rochester, MI, 2Center for Healthcare Studies, Feinberg School of Medicine, Northwestern University, 3Center for Health Statistics, University of Chicago, Chicago, IL, 4Primary Care, Brigham and Women’s Hospital, Boston, MA, 5Emergency Medicine, 6Internal Medicine, Beaumont Health, Royal Oak, MI, USA Background: Thirty-day readmission in COPD is common and costly, but potentially preventable. The emergency department (ED may be a setting for COPD readmission reduction efforts.Objective: To better understand COPD readmission through the ED, ascertain factors associated with 30-day readmission through the ED, and identify subgroups of patients with COPD for readmission reduction interventions.Patients and methods: A retrospective cohort study was conducted from January 2009 to September 2015 in patients with COPD of age ≥18 years. Electronic health record data were abstracted for information available to admitting providers in the ED. The primary outcome was readmission through the ED within 30 days of discharge from an index admission for COPD. Logistic regression was used to examine the relationship between potential risk factors and 30-day readmission.Results: The study involved 1,574 patients who presented to the ED within 30 days on an index admission for COPD. Of these, 82.2% were readmitted through the ED. Charlson score (odds ratio [OR]: 3.6; 95% CI: 2.9–4.4, a chief complaint of breathing difficulty (OR: 1.6; 95% CI: 1.1–2.6, outpatient utilization of albuterol (OR: 4.1; 95% CI: 2.6–6.4, fluticasone/salmeterol (OR: 2.3; 95% CI: 1.3–4.2, inhaled steroids (OR: 3.8; 95% CI: 1.3–10.7, and tiotropium (OR: 1.8; 95% CI: 1.0–3.2, as well as arterial blood gas (OR: 4.4; 95% CI: 1.3–15.1 and B-type natriuretic peptide (OR: 2.2; 95% CI: 1.4–3.5 testing in the

Spondilitis Tuberkulosa Cervical

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Roni Eka Saputra

2015-05-01

Full Text Available Abstrak Spondilitis tuberkulosa servikalis adalah penyakit yang cukup jarang dijumpai, hanya berkisar 2-3% dariseluruh kasus spondilitis tuberkulosa. Gambaran klinis sangat bervariasi, mulai dari gejala ringan dan tidak spesifikhingga komplikasi neurologis yang berat. Seorang wanita berusia 29 tahun datang dengan keluhan lemah keempatanggota gerak yang semakin memberat dalam 10 hari terakhir yang didahului oleh nyeri leher yang menjalar ke bahudan lengan sejak 6 bulan sebelumnya. Nyeri awalnya dirasakan sebagai keterbatasan gerakan leher saat menolehkesamping kiri dan kanan serta menundukkan kepala. Nyeri dirasakan semakin berat dengan pergerakan danberkurang jika istirahat. Pasien mengalami penurunan berat badan sejak 2 bulan terakhir. Tidak dijumpai riwayat batukatau nyeri dada. Pemeriksaan neurologis menunjukkan kelemahan  pada keempat ekstremitas. Hasil laboratoriumditemukan peningkatan Laju Endap Darah (LED. Rontgen foto toraks dalam batas normal. Roentgen foto cervicalmenunjukkan destruksi setinggi C5. MRI cervical menunjukkan destruksi pada korpus C5-6 dengan penyempitan padadiscus intervertebrae C5-6 disertai dengan  massa/abses paravertebral dengan penekanan ke posterior. MRI Thorakaltampak destruksi corpus verebre T4,5 dengan diskus intervertebralis yang menyempit. Sugestif suatu spondilitistuberkulosa. Pasien dilakukan tindakan pembedahan anterior corpectomi melalui microscopic surgery dengan graftdari iliac sinistra, serta insersi anterior plate 1 level. Hasil pemeriksaan patologi anatomi menunjukkan spodilitis TBCkaseosa. Pada spondilitis vertebre T4,5 dilakukan laminectomi, debridement costotrasversektomi, dan stabilisasidengan pedicle screw T2, T3, dan T5. Pasien diterapi dengan obat antituberkulosis. Keadaan pasien saat ini, pasiensudah bisa beraktifitas normal dengan motorik dan sensorik baik. Spondilitis tuberkulosa merupakan bentuktuberkulosa tulang yang paling sering dijumpai. Spondilitis tuberkulosa cervical berkisar 2

Výběrová šetření a analýza agregátních dat - diskuse na téma použitelnosti různých přístupů v komparativních analýzách politického chování

Czech Academy of Sciences Publication Activity Database

Kostelecký, Tomáš; Čermák, Daniel

2003-01-01

Roč. 39, č. 4 (2003), s. 529-550 ISSN 0038-0288 R&D Projects: GA ČR GA403/00/1713 Institutional research plan: CEZ:AV0Z7028912 Keywords : surveys * aggregate data analysis * ecological fallacy Subject RIV: AO - Sociology, Demography Impact factor: 0.063, year: 2003

O formoterol e uma dose média/ elevada de corticosteróides inalados são mais eficazes do que uma dose elevada de corticosteróides na asma moderada e grave

Directory of Open Access Journals (Sweden)

G. Mitchell

2003-05-01

do estudo. Este efeito pode dever-se ao antagonismo funcional do formoterol à contracção do músculo liso, à sua capacidade de estabilizar os mastócitos ou de reduzir o edema da parede brônquica.As exacerbações ligeiras e moderadas ocorreram com maior frequência no grupo sob altas doses de CT inalados. Estes resultados foram sobreponíveis aos observados anteriormente em doentes com asma ligeira submetidos à associação formoterol/budesonido (dose baixa/intermédia ou a doses elevadas deste último fármaco. Também neste estudo se verificou um maior número de exacerbações no segundo grupo.Elevadas doses de CT inalados estão relacionadas com significativos efeitos suprarrenais. Assim, a associação de um β2 agonista de longa acção (formoterol permite o controlo da doença sem necessidade de doses altas de CT inalados. Neste estudo, o quociente cortisol/creatinina urinário foi significativamente menor no grupo sob corticoterapia em dose elevada do que nos indivíduos submetidos a terapêutica combinada, traduzindo uma maior supressão do risco hipotalâmico-hipofisário no primeiro caso. Estes achados vieram confirmar a observação de que o dipropionato de beclometasona na dose≥1500 μg/dia exerce um efeito supressor significativo na libertação de cortisol endógeno.A terapêutica combinada de CT inalados e β2 agonistas de longa acção permitiu um bom controlo da asma brônquica, comparativamente a baixas doses de CT, e conduziu à administração dos fármacos inalados em doses fixas através de um dispositivo único. Ringdal e colaboradores compa-raram a eficácia do salmeterol 50 μg/ fluticasona 250 μg utilizando Diskus duas vezes/dia com o formoterol 12 μg/ budesonido 500 μg administrados separadamente através do Turbohaler duas vezes/ /dia. A primeira associação foi significativamente superior na

O formoterol e uma dose média/ elevada de corticosteróides inalados são mais eficazes do que uma dose elevada de corticosteróides na asma moderada e grave

Directory of Open Access Journals (Sweden)

G. Mitchell

2004-09-01

do estudo. Este efeito pode dever-se ao antagonismo funcional do formoterol à contracção do músculo liso, à sua capacidade de estabilizar os mastócitos ou de reduzir o edema da parede brônquica.As exacerbações ligeiras e moderadas ocorreram com maior frequência no grupo sob altas doses de CT inalados. Estes resultados foram sobreponíveis aos observados anteriormente em doentes com asma ligeira submetidos à associação formoterol/budesonido (dose baixa/intermédia ou a doses elevadas deste último fármaco. Também neste estudo se verificou um maior número de exacerbações no segundo grupo.Elevadas doses de CT inalados estão relacionadas com significativos efeitos suprarrenais. Assim, a associação de um β2 agonista de longa acção (formoterol permite o controlo da doença sem necessidade de doses altas de CT inalados. Neste estudo, o quociente cortisol/creatinina urinário foi significativamente menor no grupo sob corticoterapia em dose elevada do que nos indivíduos submetidos a terapêutica combinada, traduzindo uma maior supressão do risco hipotalâmico-hipofisário no primeiro caso. Estes achados vieram confirmar a observação de que o dipropionato de beclometasona na dose≥1500 μg/dia exerce um efeito supressor significativo na libertação de cortisol endógeno.A terapêutica combinada de CT inalados e β2 agonistas de longa acção permitiu um bom controlo da asma brônquica, comparativamente a baixas doses de CT, e conduziu à administração dos fármacos inalados em doses fixas através de um dispositivo único. Ringdal e colaboradores compararam a eficácia do salmeterol 50 μg/ fluticasona 250 μg utilizando Diskus duas vezes/dia com o formoterol 12 μg/ budesonido 500 μg administrados separadamente através do Turbohaler duas vezes/ /dia. A primeira associação foi significativamente superior na

Úvodník

Directory of Open Access Journals (Sweden)

Jana Dlouhá

2013-10-01

Full Text Available Vážení čtenáři Envigogiky, jak máme ve zvyku, představujeme nové právě vycházející číslo (2013/VIII/3 v souvislostech širších, dosvědčujících směr našeho společného usilování. V tomto podzimním čase se dotkneme často diskutovaného problému elit a jejich postavení v současné společnosti výkonu, a pravidelně opakovaných námitek, že současná společnost elity jakoby nepotřebuje, a ani nevytváří[1]. Intelektuální elitou je vždy míněna vrstva lidí s rozhledem, sečtělých, schopných uvažovat v souvislostech; to vše jsou schopnosti vznikající ve svobodě – nejen smýšlení, tedy názoru a jeho vyjádření, ale především myšlení samého. Tato svoboda potřebuje otevření časového prostoru, kdy myšlení je samo sebou – může volně plynout, aniž by naráželo na své, či spíše vnější „produktivní“ nároky. Čas pro čtení, rozvažování či dokonce rozjímání chybí stále více, což je spojeno s nedůvěrou, že by takové počínání mohlo vůbec „k něčemu vést“. Také environmentální vzdělání vede v tomto ohledu bitvu předem ztracenou – pokouší se vyvzdorovat tento volný čas v systému požírajícímu naše děti již v útlém věku, a obhájit jej proti soustavnému nároku na vytváření nových znalostí. Jenomže co to je znalost: správně zodpovězená položka v dotazníku, výsledek testu? Souvisí v naší „znalostní společnosti“ opravdu přímo s (osobním úspěchem? Skutečné poznání je třeba nejen nabýt, ale také pro sebe strávit, vystavit zkoušce při střetu se skutečností, obhájit v diskusi… To vše postupně zdegenerovalo v pouhou schopnost použít je pro tvorbu požadovaného produktu, ať jím je publikovaný text, prezentace, nebo jen ukončená vzdělávací jednotka vykazatelná v CV. Že by se dalo poznávat „jen tak“, při četbě, procházkách krajinou a diskusích s přáteli, se zd

Revisão sistemática do efeito dos broncodilatadores na capacidade para o exercício em doentes com DPOC

Directory of Open Access Journals (Sweden)

J.J.W. Liesker

2002-03-01

éfico significativo na maior parte dos estudos, quer sobre o exercício com cargas incrementais quer com cargas constantes, com uma tendência para um efeito mais benéfico quando são utilizadas doses mais elevadas (superior a 80 μg. Não foram analisados estudos com o tiotrópio.Em mais de dois terços dos estudos, os agentes β2 agonistas com início de acção rápido apresentaram efeitos favoráveis à capacidade para o exercício. Surpreendentemente, o efeito dos β2 agonistas de longa duração (salmeterol e formoterol foi menos claro nos estudos realizados.A maior parte dos estudos realizados com as teofilinas não demonstraram efeitos significativos sobre a capacidade para o exercício.O número de estudos realizado é insuficiente para poder comparar, de forma directa, as diferentes classes de broncodilatadores, com vista a uma escolha racional, mas, em conjunto, o número de estudos favoráveis ao uso dos anticolinérgicos e dos agonistas β2 adrenérgicos é superior ao número de estudos favoráveis ao uso das teofilinas na melhoria da capacidade para o exercício.Alguns estudos utilizaram uma combinação de dois tipos de broncodilatadores, e demonstraram melhoria da capacidade para o exercício, quando comparados com o uso dos broncodilatadores em monoterapia ou com o placebo. São exemplo o uso combinado de salbutamol com brometo de ipratrópio na prova de marcha e no exercício com cargas crescentes, ou o uso de ipratrópio com teofilina.A maior parte dos estudos que utilizou a avaliação da dispneia reportou melhoria com o uso dos bron-codilatadores, mesmo quando esta não se acompanhou de melhoria da limitação do débito das vias aéreas ou da capacidade para o exercício. Os broncodilatadores utilizados nestes estudos foram os anticolinérgicos e os agonistas β2 adrenérgicos.Em cinco dos seis estudos que compararam o efeito dos broncodilatadores em exerc