Bronchodilator aminophylline may induce atrial or less often ventricular arrhythmias. The mechanism of this proarrhythmic side effect has not been fully explained. Modifications of inward rectifier potassium (Kir) currents including IK1 are known to play an important role in arrhythmogenesis; however, no data on the aminophylline effect on these currents have been published. Hence, we tested the effect of aminophylline (3-100 µM) on IK1 in enzymatically isolated rat ventricular myocytes using the whole-cell patch-clamp technique. A dual steady-state effect of aminophylline was observed; either inhibition or activation was apparent in individual cells during the application of aminophylline at a given concentration. The smaller the magnitude of the control IK1, the more likely the activation of the current by aminophylline and vice versa. The effect was reversible; the relative changes at -50 and -110 mV did not differ. Using IK1 channel population model, the dual effect was explained by the interaction of aminophylline with two different channel populations, the first one being inhibited and the second one being activated. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells could be simulated. We propose that the dual aminophylline effect may be related to the direct and indirect effect of the drug on various Kir2.x subunits forming the homo- and heterotetrameric IK1 channels in a single cell. The observed IK1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

• Klíčová slova
• Aminophylline, Arrhythmia, Dual effect, Fibrillation, Inward rectifier, Population channel model,
• MeSH
• aminofylin škodlivé účinky   MeSH
• bronchodilatancia škodlivé účinky   MeSH
• draslík farmakologie   MeSH
• draslíkové kanály dovnitř usměrňující * MeSH
• kardiomyocyty fyziologie   MeSH
• krysa rodu Rattus MeSH
• srdeční arytmie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminofylin MeSH
• bronchodilatancia MeSH
• draslík MeSH
• draslíkové kanály dovnitř usměrňující * MeSH

BACKGROUND: The Clinical COPD Questionnaire (CCQ) is a simple patient-reported tool to measure clinical control of chronic obstructive pulmonary disease (COPD). OBJECTIVE: This open-label, single-arm, non-interventional study (NCT03663569) investigated changes in CCQ score during treatment with tiotropium/olodaterol in clinical practice. METHODS: Data were included from consenting COPD patients, enrolled in Bulgaria, Czech Republic, Hungary, Israel, Lithuania, Poland, Romania, Russia, Slovenia, Switzerland and Ukraine, who were receiving a new prescription for tiotropium/olodaterol according to the treating physician in a real-world environment. The primary endpoint was the occurrence of therapeutic success, defined as a 0.4-point decrease in CCQ score after treatment with tiotropium/olodaterol for approximately 6 weeks. RESULTS: Overall, 4819 patients were treated; baseline and Week 6 CCQ scores were available for 4700 patients, mostly classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B (51.6%) or D (42.7%). After 6 weeks' treatment, 81.4% (95% confidence interval [95% CI] 80.24-82.49) of patients achieved therapeutic success; mean improvement in overall CCQ score was 1.02 points (95% CI 1.00-1.05). Improved CCQ score was seen in 92.2% of patients (95% CI 91.43-92.98), 2.5% had no change and 5.3% showed a worsening. When stratified by prior treatment, the greatest benefit was seen in treatment-naïve patients, with 85.7% achieving therapeutic success, compared with 79.5% of those pretreated with long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) and 74.2% of those pretreated with LABA or long-acting muscarinic antagonist (LAMA) monotherapy. Overall, rescue medication decreased by 1.25 puffs/day (95% CI 1.19-1.31) versus baseline. In total, 29 patients (0.6%) reported drug-related adverse events and 7 patients reported serious adverse events (0.15%). CONCLUSION: In 4700 COPD patients, 6 weeks' treatment with tiotropium/olodaterol, as initial treatment or follow-up to LAMA or LABA monotherapy or LABA/ICS, improved CCQ and decreased rescue medication use. The adverse event profile was consistent with the known safety profile of tiotropium/olodaterol.

• Klíčová slova
• CCQ *, COPD *, Clinical COPD Questionnaire *, non-interventional study *, olodaterol *, tiotropium *,
• MeSH
• agonisté beta-2-adrenergních receptorů škodlivé účinky   MeSH
• antagonisté muskarinových receptorů škodlivé účinky   MeSH
• aplikace inhalační MeSH
• benzoxaziny terapeutické užití   MeSH
• bronchodilatancia škodlivé účinky   MeSH
• chronická obstrukční plicní nemoc * diagnóza   farmakoterapie   MeSH
• fixní kombinace léků MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• tiotropium bromid škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• klinické zkoušky MeSH
• Geografické názvy
• Bulharsko MeSH
• Česká republika MeSH
• Izrael MeSH
• Maďarsko MeSH
• Polsko MeSH
• Rumunsko MeSH
• Rusko MeSH
• Švýcarsko MeSH
• Názvy látek
• agonisté beta-2-adrenergních receptorů MeSH
• antagonisté muskarinových receptorů MeSH
• benzoxaziny MeSH
• bronchodilatancia MeSH
• fixní kombinace léků MeSH
• olodaterol MeSH Prohlížeč
• tiotropium bromid MeSH

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

• Klíčová slova
• LABA, LAMA, anticholinergic, dual bronchodilation, inhaled corticosteroid, tiotropium,
• MeSH
• agonisté beta-2-adrenergních receptorů aplikace a dávkování   škodlivé účinky   MeSH
• antagonisté muskarinových receptorů aplikace a dávkování   škodlivé účinky   MeSH
• aplikace inhalační MeSH
• bronchodilatancia aplikace a dávkování   škodlivé účinky   MeSH
• chronická obstrukční plicní nemoc diagnóza   farmakoterapie   patofyziologie   MeSH
• hormony kůry nadledvin aplikace a dávkování   škodlivé účinky   MeSH
• kvalita života MeSH
• lidé MeSH
• obnova funkce MeSH
• plíce účinky léků   patofyziologie   MeSH
• progrese nemoci MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• tolerance zátěže účinky léků   MeSH
• výsledek terapie MeSH
• zdravotní stav MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• agonisté beta-2-adrenergních receptorů MeSH
• antagonisté muskarinových receptorů MeSH
• bronchodilatancia MeSH
• hormony kůry nadledvin MeSH

Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.

• Klíčová slova
• Bronchitis, Emphysema, Exacerbation, Guidelines, Phenotypes, Prevention, Risk factors, Treatment,
• MeSH
• agonisté beta-2-adrenergních receptorů škodlivé účinky   terapeutické užití   MeSH
• antagonisté muskarinových receptorů škodlivé účinky   terapeutické užití   MeSH
• antibakteriální látky terapeutické užití   MeSH
• bronchodilatancia škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• chronická obstrukční plicní nemoc diagnóza   farmakoterapie   patofyziologie   MeSH
• expektorancia terapeutické užití   MeSH
• fenotyp MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• inhibitory fosfodiesterasy 4 terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• mukociliární clearance účinky léků   MeSH
• plíce účinky léků   patofyziologie   MeSH
• progrese nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• agonisté beta-2-adrenergních receptorů MeSH
• antagonisté muskarinových receptorů MeSH
• antibakteriální látky MeSH
• bronchodilatancia MeSH
• expektorancia MeSH
• hormony kůry nadledvin MeSH
• inhibitory fosfodiesterasy 4 MeSH

BACKGROUND: Umeclidinium and vilanterol, long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease, are primarily eliminated via the hepatic route; however, severe renal impairment may adversely affect some elimination pathways other than the kidney. OBJECTIVES: To evaluate the effect of severe renal impairment on the pharmacokinetics of umeclidinium and umeclidinium/vilanterol. METHODS: Nine patients with severe renal impairment (creatinine clearance <30 mL/min) and nine matched healthy volunteers received a single dose of umeclidinium 125 μg; and after a 7- to 14-day washout, a single dose of umeclidinium/vilanterol 125/25 μg. RESULTS: No clinically relevant increases in plasma umeclidinium or vilanterol systemic exposure (area under the curve or maximum observed plasma concentration) were observed following umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration. On average, the amount of umeclidinium excreted in 24 hours in urine (90% confidence interval) was 88% (81%-93%) and 89% (81%-93%) lower in patients with severe renal impairment compared with healthy volunteers following umeclidinium 125 μg and umeclidinium/vilanterol 125/25 μg administration, respectively. Treatments were well tolerated in both populations. CONCLUSION: Umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration to patients with severe renal impairment did not demonstrate clinically relevant increases in systemic exposure compared with healthy volunteers. No dose adjustment for umeclidinium and umeclidinium/vilanterol is warranted in patients with severe renal impairment.

• Klíčová slova
• GSK573719, chronic obstructive pulmonary disease, exposure, long-acting beta2 agonist, long-acting muscarinic antagonist,
• MeSH
• agonisté beta-2-adrenergních receptorů aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• antagonisté muskarinových receptorů aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• aplikace inhalační MeSH
• benzylalkoholy aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• bronchodilatancia aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• chinuklidiny aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• chlorbenzeny aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• dospělí MeSH
• eliminace ledvinami MeSH
• fixní kombinace léků MeSH
• jednoduchá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci ledvin diagnóza   metabolismus   MeSH
• plocha pod křivkou MeSH
• práškové inhalátory MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Maďarsko MeSH
• Názvy látek
• agonisté beta-2-adrenergních receptorů MeSH
• antagonisté muskarinových receptorů MeSH
• benzylalkoholy MeSH
• bronchodilatancia MeSH
• chinuklidiny MeSH
• chlorbenzeny MeSH
• fixní kombinace léků MeSH
• GSK573719 MeSH Prohlížeč
• vilanterol MeSH Prohlížeč

UNLABELLED: We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. CONCLUSION: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.

• MeSH
• agonisté adrenergních beta-receptorů škodlivé účinky   terapeutické užití   MeSH
• bronchiální astma farmakoterapie   metabolismus   patofyziologie   MeSH
• bronchodilatancia škodlivé účinky   terapeutické užití   MeSH
• budesonid škodlivé účinky   terapeutické užití   MeSH
• dítě MeSH
• dvojitá slepá metoda MeSH
• ethanolaminy škodlivé účinky   terapeutické užití   MeSH
• fixní kombinace léků MeSH
• formoterol fumarát MeSH
• hydrokortison krev   moč   MeSH
• kombinovaná farmakoterapie MeSH
• kvalita života MeSH
• lidé MeSH
• usilovný výdechový objem účinky léků   MeSH
• vrcholová exspirační průtoková rychlost účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• agonisté adrenergních beta-receptorů MeSH
• bronchodilatancia MeSH
• budesonid MeSH
• ethanolaminy MeSH
• fixní kombinace léků MeSH
• formoterol fumarát MeSH
• hydrokortison MeSH

The authors compared in a prospective study the bronchodilatating and undesirable effects of combined inhalation treatment (phenoterol + ipratropium bromide) in the treatment of patients with exacerbation of chronic obstructive pulmonary disease, using different dosages. The patients were divided at random into two groups--group one inhaled berodual sol 3.5 ml/day (i.e. 1.75 mg phenoteroli + 0.875 mg ipratropii bromidium), the second group had a dose of double size. During the trial the authors monitored the peak expiration rate, the heart and respiration rate, blood gases and the subjective state of dyspnoea, using a 10 cm line. By comparison of bronchodilatating and undesirable effects they reached the conclusion that a daily dose of 3.5 ml berodual sol. is sufficiently effective. Increasing the daily dose to 7 ml did not produce a greater therapeutic effect nor increase the risk of undesirable effects.

• MeSH
• aplikace inhalační MeSH
• bronchodilatancia aplikace a dávkování   škodlivé účinky   MeSH
• fenoterol aplikace a dávkování   škodlivé účinky   MeSH
• ipratropium aplikace a dávkování   škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• obstrukční plicní nemoci farmakoterapie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• bronchodilatancia MeSH
• fenoterol MeSH
• ipratropium MeSH

The bronchodilatating effect of one single dose of Berotec, Berodual and Atrovent, has been studied in 28 patients suffering from bronchial asthma. All three drugs had a beneficial bronchodilatating effect lasting for 300 minutes. There were no statistically significant changes between the drugs studied.

• MeSH
• bronchiální astma farmakoterapie   MeSH
• bronchodilatancia * škodlivé účinky   MeSH
• deriváty atropinu farmakologie   MeSH
• dospělí MeSH
• fenoterol škodlivé účinky   farmakologie   MeSH
• fixní kombinace léků škodlivé účinky   farmakologie   MeSH
• ipratropium škodlivé účinky   farmakologie   MeSH
• lidé MeSH
• pulz účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• bronchodilatancia * MeSH
• deriváty atropinu MeSH
• fenoterol, ipratropium drug combination MeSH Prohlížeč
• fenoterol MeSH
• fixní kombinace léků MeSH
• ipratropium MeSH