Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 832
Filtrar
1.
Biochem Med (Zagreb) ; 30(1): 010701, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839721

RESUMO

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that can affect haemostasis. This study aimed to determine differences in platelet-related parameters between controls and COPD subjects. The hypothesis was that platelet indices are disturbed in COPD patients, and this would be accompanied by increased C-reactive protein (CRP), fibrinogen (Fbg) and white blood cells (WBC). Therefore, platelet count (Plt), platelet-related parameters - mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), platelet to lymphocyte ratio (PLR), Plt index as well as CRP, Fbg and WBC were assessed. Materials and methods: Study included 109 patients with stable COPD and 95 control subjects, recruited at Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb (Zagreb, Croatia). Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. Results: Platelet (P = 0.007) and PLR (P = 0.006) were increased, while other platelet indices were decreased in COPD patients compared to controls. Combined model that included PLR, PDW and WBC showed great diagnostic performances, and correctly classified 75% of cases with an AUC of 0.845 (0.788 - 0.892), P < 0.001. Comorbidities (cardiovascular or metabolic diseases) had no effect on investigated parameters, while inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) therapy increased MPV and PDW values in COPD patients. Conclusion: Platelet indices were altered in COPD patients and they could be valuable as diagnostic markers of COPD development, especially if combined with already known inflammatory markers.


Assuntos
Biomarcadores/sangue , Plaquetas/citologia , Doença Pulmonar Obstrutiva Crônica/patologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Leucócitos/citologia , Modelos Logísticos , Linfócitos/citologia , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
2.
Tidsskr Nor Laegeforen ; 139(17)2019 Nov 19.
Artigo em Norueguês | MEDLINE | ID: mdl-31746168

RESUMO

BACKGROUND: Since their introduction more than 50 years ago, use of ß-agonists for inhalation has been associated with increased mortality. Since the turn of the century, particular concern has been voiced regarding long-acting ß2-selective agonists. Our purpose was to investigate the evidence from recently published randomised trials of possible increased risks of death and serious adverse events related to exposure to these drugs. MATERIAL AND METHOD: A PubMed search identified ten clinical trials which fulfilled predefined inclusion criteria. RESULTS: The ten trials encompassed 66 664 patients. A total of 16 asthma-related deaths after exposure to long-acting ß2-selective agonists were recorded among 33 043 actively treated patients, whereas four such deaths were recorded among the 33 621 patients in the control groups. A single, large, pragmatic trial accounts for a majority of these fatalities. INTERPRETATION: Exposure to long-acting ß2-selective agonists is associated with a small increase in mortality. Whether concomitant use of inhalation steroids fully reverses this effect is not clear.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Asma , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas Adrenérgicos beta , Asma/tratamento farmacológico , Humanos , Esteroides
3.
FP Essent ; 486: 26-32, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31710455

RESUMO

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by cough, dyspnea, and sputum production caused by inhalation of harmful chemicals, such as tobacco smoke. COPD should be suspected in patients with a significant smoking history, shortness of breath, and sputum production. The diagnosis is made by spirometry. A forced expiratory volume in the first second of expiration to forced vital capacity (FEV1/FVC) ratio of less than 0.7 after bronchodilator administration confirms the diagnosis. Therapy for patients with stable COPD should include a bronchodilator, either a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). For patients who continue to experience dyspnea with a single bronchodilator, dual therapy with a LABA and LAMA is appropriate. For patients with continued exacerbations, inhaled corticosteroids can be added to LABA-LAMA therapy. Acute exacerbations are characterized by a worsening of symptoms that requires additional therapy. Short-acting beta2-agonists with or without short-acting muscarinic antagonists are the basic therapy for acute exacerbations of COPD. Systemic glucocorticoids have been shown to shorten exacerbations and improve lung function. Antibiotics have been shown to reduce rates of treatment failure and sputum purulence. Noninvasive mechanical ventilation is preferred for patients with respiratory failure.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
5.
Herz ; 44(6): 517-521, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297545

RESUMO

Chronic heart and lung diseases are very common in the elderly population. The combination of chronic heart failure and chronic obstructive pulmonary disease (COPD) is also common and, according to current guidelines, these patients should be treated for both diseases. In patients with heart failure, beta-blockers are very important drugs because their use is associated with significantly improved morbidity and mortality. These beneficial effects were documented in patients with and without COPD, although theoretically there is a risk for bronchoconstriction, particularly with non-beta1 selective blockers. In COPD patients, long-acting sympathomimetics (LABA) improve lung function, dyspnea, and quality of life and their combination with a beta-blocker makes sense from a pharmacological and a clinical point of view, because any potential arrhythmogenic effects of the LABA will be ameliorated by the beta-blocker. Inhaled tiotropium, a long-acting muscarinic antagonist (LAMA), has been extensively investigated and no safety concerns were reported in terms of cardiac adverse effects. The same applies for the other approved LAMA preparations and LAMA-LABA combinations. Severe COPD causes air-trapping with increasing pressures in the thorax, leading to limitations in blood return into the thorax from the periphery of the body. This causes a decrease in stroke volume and cardiac index and is associated with dyspnea. All these adverse effects can be ameliorated by potent anti-obstructive therapy as recently shown by means of a LABA-LAMA combination.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Interações de Medicamentos , Humanos , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida
6.
Respir Res ; 20(1): 141, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286970

RESUMO

There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease. This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls. However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials. Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Volume Expiratório Forçado/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Tolerância ao Exercício/fisiologia , Volume Expiratório Forçado/fisiologia , Humanos , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Resultado do Tratamento
9.
Ter Arkh ; 91(3): 76-85, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31094464

RESUMO

Currently, combinations of long-acting beta2-agonists and long-acting anticholinergics are considered as the basic therapy for majority of patients with chronic obstructive pulmonary disease (COPD). These combinations have different pharmacological characteristics and delivery devices that provides different clinical effects and new opportunities for personalized treatment of COPD. Aclidinium/formoterol fixed combination differs from other dual bronchodilators by twice-daily dosing regimen, good safety profile and a specific delivery system. Recent information on clinical efficacy and safety of aclidinium/formoterol combination in COPD patients is given in this article.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/uso terapêutico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Combinação de Medicamentos , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/efeitos adversos , Humanos , Pulmão/fisiopatologia , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Resultado do Tratamento , Tropanos/administração & dosagem , Tropanos/efeitos adversos
10.
Drugs ; 79(9): 997-1008, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31119643

RESUMO

Tiotropium/olodaterol (Stiolto® Respimat®; Spiolto® Respimat®) is an inhaled fixed-dose combination of the long-acting muscarinic antagonist tiotropium bromide (hereafter referred to as tiotropium) and the long-acting ß2-adrenergic agonist olodaterol. It is available in several countries, including the USA, Japan, China and those of the EU, where it is indicated for the long-term maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy of tiotropium/olodaterol 5/5 µg/day in patients with COPD was evaluated in phase III or IV trials of 6-52 weeks' duration. Tiotropium/olodaterol improved lung function to a greater extent than each of its individual components or placebo in 12- and 52-week trials. In 6-week trials, tiotropium/olodaterol provided greater lung function benefits over 24 h than the individual components, placebo or twice-daily fluticasone propionate/salmeterol. Tiotropium/olodaterol also demonstrated beneficial effects on health-related quality of life (HR-QoL), dyspnoea, inspiratory capacity, exercise endurance and the need for rescue medication. In an 8-week open-label trial, umeclidinium/vilanterol was superior to tiotropium/olodaterol for the primary endpoint of trough forced expiratory volume in 1 s. The tolerability profile of tiotropium/olodaterol was generally similar to that of the individual components. In conclusion, tiotropium/olodaterol provides a useful option for the maintenance treatment of COPD, with the convenience of once-daily administration via a single inhaler.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Benzoxazinas/farmacologia , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Fase IV como Assunto , Combinação de Medicamentos , Humanos , Antagonistas Muscarínicos/farmacologia , Qualidade de Vida , Brometo de Tiotrópio/farmacologia , Resultado do Tratamento
11.
Ter Arkh ; 91(1): 78-83, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090376

RESUMO

AIM: The aim of the study. To estimate the effectiveness of clinical patients register implementation as well as to analyze different treatment and prophylactic programs on chronic obstructive pulmonary disease (COPD) patients' structure. MATERIALS AND METHODS: The COPD patient's register consists of 4257 cases. Spirometrical data were evaluated. Dynamic follow was performed on 567 COPD patients. Bronchodilator's therapy was estimated as well as combined inhaled corticosteroid/ long acting ß2-agonist medications and vaccination against pneumococcal infection. RESULTS: Computer program "Electronic polyclinic" proposed by the authors of this article is effective in precision of diagnostic decision making in cohort study, dynamic follow up after clinical symptoms, evaluation of instrumental and laboratory results, prophylactics and treatment effectiveness, "clinical patients registers" automatic formation using syndrome or nosological principle, checking the COPD patients in the group of those with bronchial obstruction. CONCLUSION: Positive effects of long-acting bronchodilator treatment on COPD exacerbation decreasing and more expressed effect of inhaled corticosteroid/ long acting ß2-agonists were confirmed. More interesting result was influence of vaccination against pneumococcal infection PCV13 (polyvalent conjugated vaccine) on exacerbation frequency and dyspnea severity.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Broncodilatadores/efeitos adversos , Broncodilatadores/uso terapêutico , Estudos de Coortes , Seguimentos , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sistema de Registros , Resultado do Tratamento
12.
J Korean Med Sci ; 34(15): e120, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31001937

RESUMO

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.


Assuntos
Asma/terapia , Termoplastia Brônquica , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Asma/diagnóstico , Asma/tratamento farmacológico , Broncoscopia , Feminino , Fluoroquinolonas/uso terapêutico , Fluticasona/uso terapêutico , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Xinafoato de Salmeterol/uso terapêutico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
13.
Artigo em Inglês | MEDLINE | ID: mdl-31015757

RESUMO

Purpose: The aim of this study was to investigate the comparative risks of budesonide/formoterol, versus placebo or monotherapies, for the treatment of patients with stable COPD. Materials and methods: We undertook a systematic search of the literature in PubMed, Embase, and the Cochrane Central Register of Controlled Trials, for randomized controlled trials (RCTs) comparing budesonide/formoterol with control regimens for the treatment of patients with stable COPD and at least 12 weeks of follow-up, meeting the inclusion criteria. Studies were reviewed, and OR with corresponding 95% CI was used to pool the results. Results: A total of eight studies involving 9,254 patients met the inclusion criteria of this meta-analysis. Compared with placebo, combination therapy with budesonide/formoterol was associated with a significantly higher risk of adverse effects including oral candidiasis (OR: 3.09, 95% CI: 1.95-4.91) and dysphonia (OR: 2.76, 95% CI: 1.40-5.44), but not pneumonia (OR: 0.94, 95% CI: 0.64-1.37) or bronchitis (OR: 1.36, 95% CI: 0.95-1.95). A similar pattern was also evident for the comparison of formoterol with budesonide/formoterol, with increased occurrence of oral candidiasis (OR: 2.72, 95% CI: 1.33-5.58) and dysphonia (OR: 4.13, 95% CI: 1.95-8.76); however, there were no significant differences in pneumonia (OR: 1.31, 95% CI: 0.98-1.74) or bronchitis (OR: 1.05, 95% CI: 0.83-1.31). In contrast, compared with budesonide, combined budesonide/formoterol was associated with similar risks of adverse effects, including pneumonia (OR: 1.20, 95% CI: 0.60-2.39), bronchitis (OR: 0.95, 95% CI: 0.41-2.20), oral candidiasis (OR: 0.79, 95% CI: 0.41-1.53), and dysphonia (OR: 1.00, 95% CI: 0.40-2.47). Conclusion: Combination therapy does not cause more adverse events, including pneumonia and bronchitis, than control (placebo, formoterol, or budesonide) treatment in patients with stable COPD, while there were higher risks of oral candidiasis and dysphonia compared with the non-inhaled corticosteroid group (placebo, formoterol).


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Glucocorticoides/uso terapêutico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/efeitos adversos , Combinação Budesonida e Fumarato de Formoterol/efeitos adversos , Glucocorticoides/efeitos adversos , Humanos , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento
14.
Ann Allergy Asthma Immunol ; 123(1): 57-63.e2, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028894

RESUMO

BACKGROUND: In 2004, the landmark Gaining Optimal Asthma Control (GOAL) study demonstrated that most patients can achieve asthma control through sustained treatment and that adding a long-acting ß2-adrenoreceptor agonist to an inhaled corticosteroid (ICS) is more effective than ICS alone in this regard. Definitions of asthma control have since evolved, and the consequent implications for the GOAL study findings are unclear. OBJECTIVE: To evaluate the efficacy of fluticasone propionate and salmeterol and fluticasone propionate alone in achieving and maintaining asthma control, as derived from the Global Initiative for Asthma (GINA) 2016 report. METHODS: In total, 3416 patients were stratified by prior medication (ICS-naive [stratum 1], low-dose ICS [stratum 2], or medium-dose ICS [stratum 3]) and randomized to receive fluticasone propionate and salmeterol or fluticasone propionate. The primary end point was the proportion of patients achieving well-controlled or partly controlled asthma; secondary end points included the proportion of patients achieving well-controlled asthma. Control was evaluated during the last 4 weeks of each dose titration. RESULTS: In all strata, more patients achieved well-controlled or partly controlled asthma with fluticasone propionate and salmeterol vs fluticasone propionate alone (stratum 1: 91% vs 85%; P = .003; stratum 2: 86% vs 82%; P = .07; and stratum 3: 76% vs 66%; P < .001), as well as patients with well-controlled asthma (stratum 1: 64% vs 56%; P = .005; stratum 2: 59% vs 41%; P < .001; and stratum 3: 40% vs 22%; P < .001). CONCLUSION: A markedly higher proportion of patients with uncontrolled asthma in each stratum achieved control according to GINA 2016 criteria compared with the original study criteria. The proportion of patients achieving control remained greater with fluticasone propionate and salmeterol than with fluticasone propionate alone.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Fluticasona/uso terapêutico , Xinafoato de Salmeterol/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada/métodos , Humanos
15.
Expert Opin Pharmacother ; 20(9): 1075-1085, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30983423

RESUMO

INTRODUCTION: Inhaled corticosteroid/long-acting ß-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients. Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed. Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Androstadienos/uso terapêutico , Álcoois Benzílicos/uso terapêutico , Clorobenzenos/uso terapêutico , Combinação de Medicamentos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Androstadienos/farmacologia , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia
16.
Mol Med Rep ; 19(5): 4027-4034, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942450

RESUMO

MicroRNAs (miRNAs) are non­coding RNAs of ~22 nucleotides in length, which serve an important role in numerous diseases. Asthma is a chronic airway inflammatory disease, which is the most common chronic disease among children. The role of miRNA (miR)­16 in asthma is unclear. The objective of the present study was to examine the underlying molecular mechanism of the involvement of miR­16 in asthma. A total of 72 volunteers diagnosed with asthma consented to participate in the study, of whom 52 participants were identified to be sensitive to salmeterol and 20 participants were identified to be resistant to salmeterol. Receiver operating characteristic (ROC) curve analysis was performed to compare the expression levels of serum miR­16 between the sensitive and resistant groups, and to confirm the association between the expression level of serum miR­16 and forced expiratory volume in 1 sec (FEV1). In silico analysis, a luciferase assay, reverse transcription­quantitative polymerase chain reaction analysis and western blotting were performed to elucidate the molecular mechanism underlying the role of miR­16 in asthma. ROC results demonstrated that the serum miR­16 level may function as a biomarker to predict the response to salmeterol therapy, and the miR­16 expression level displayed a significant negative correlation with FEV1. According to the in silico analysis, adrenoreceptor ß­2 (ADRB2) was a direct target of miR­16, and it was further confirmed by luciferase assay that 25 nM miR­16 mimic had an inhibitory effect on the luciferase activity of the wild­type ADRB2 3' untranslated region (UTR); the inhibitory effect on the luciferase activity of the wild­type ADRB2 3'UTR was stronger with 50 nM miR­16 mimic, and strongest with 75 nM miR­16 mimic, whereas the luciferase activity of the mutant ADRB2 3'UTR in cells was similar following treatment with 0, 25, 50 or 75 nM miR­16 mimic. miR­16 reduced the mRNA and protein expression levels of ADRB2 in a dose­dependent manner. These results identified that miR­16 may be used as a predictive biomarker of therapeutic response in asthma.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Asma/tratamento farmacológico , MicroRNAs/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Regiões 3' não Traduzidas , Adolescente , Adulto , Antagomirs/metabolismo , Área Sob a Curva , Asma/metabolismo , Asma/patologia , Criança , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , MicroRNAs/genética , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Curva ROC , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/genética , Xinafoato de Salmeterol/farmacologia , Xinafoato de Salmeterol/uso terapêutico , Regulação para Cima , Adulto Jovem
17.
J Pharmacol Exp Ther ; 369(2): 188-199, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30819762

RESUMO

The anabolic effects of ß 2-adrenoceptor (ß 2-AR) agonists on skeletal muscle have been demonstrated in various species. However, the clinical use of ß 2-AR agonists for skeletal muscle wasting conditions has been limited by their undesired cardiovascular effects. Here, we describe the preclinical pharmacological profile of a novel 5-hydroxybenzothiazolone (5-HOB) derived ß 2-AR agonist in comparison with formoterol as a representative ß 2-AR agonist that have been well characterized. In vitro, 5-HOB has nanomolar affinity for the human ß 2-AR and selectivity over the ß 1-AR and ß 3-AR. 5-HOB also shows potent agonistic activity at the ß 2-AR in primary skeletal muscle myotubes and induces hypertrophy of skeletal muscle myotubes. Compared with formoterol, 5-HOB demonstrates comparable full-agonist activity on cAMP production in skeletal muscle cells and skeletal muscle tissue-derived membranes. In contrast, a greatly reduced intrinsic activity was determined in cardiomyocytes and cell membranes prepared from the rat heart. In addition, 5-HOB shows weak effects on chronotropy, inotropy, and vascular relaxation compared with formoterol. In vivo, 5-HOB significantly increases hind limb muscle weight in rats with attenuated effects on heart weight and ejection fraction, unlike formoterol. Furthermore, changes in cardiovascular parameters after bolus subcutaneous treatment in rats and rhesus monkeys are significantly lower with 5-HOB compared with formoterol. In conclusion, the pharmacological profile of 5-HOB indicates superior tissue selectivity compared with the conventional ß 2-AR agonist formoterol in preclinical studies and supports the notion that such tissue-selective agonists should be investigated for the safe treatment of muscle-wasting conditions without cardiovascular limiting effects.


Assuntos
Benzotiazóis/química , Benzotiazóis/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Segurança , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/química , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anabolizantes/efeitos adversos , Anabolizantes/química , Anabolizantes/farmacologia , Anabolizantes/uso terapêutico , Animais , Benzotiazóis/efeitos adversos , Benzotiazóis/uso terapêutico , Células CHO , Cricetulus , Coração/efeitos dos fármacos , Humanos , Hipertrofia/tratamento farmacológico , Cinética , Macaca mulatta , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Miócitos Cardíacos/efeitos dos fármacos , Ratos
18.
Eur J Clin Pharmacol ; 75(7): 1025-1032, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30903196

RESUMO

PURPOSE: A subset of patients with chronic obstructive pulmonary disease (COPD) experience a decrease in exacerbation frequency, leading to a diminished need for treatment with inhaled corticosteroids (ICS). We investigated prescribing and discontinuation patterns of long-acting bronchodilators and ICS in COPD patients according to exacerbation frequency. METHODS: Using the nationwide Danish health registries, we conducted a drug utilization study among patients who had at least two exacerbations or one hospitalization due to an exacerbation during 2011-2012. This study population was stratified according to consistency of exacerbation occurrence after 12, 24, 36, and 48 months of follow-up and the groups were described according to use of ICS, long-acting ß2-agonists (LABA), and long-acting anticholinergics (LAMA), and combinations thereof. RESULTS: We identified 29,010 COPD exacerbators during 2011-2012. Upon inclusion, 70% received ICS-containing regimens, in combination with LABA (23%) or both LABA and LAMA (41%). The proportion of prevalent users of ICS-containing regimens decreased to 56% during follow-up among exacerbation-free individuals, while it increased to 86% in individuals who experienced at least one exacerbation annually. Persistence to ICS-containing regimens was 58% after 4 years in individuals without exacerbations compared to 74% among those with annual exacerbations. Similar patterns were observed for triple therapy which was the most extensively used drug combination regardless of consistency of exacerbation occurrence. CONCLUSIONS: The extensive use of ICS and the relatively high persistence to ICS-containing regimens in individuals who had a decrease in exacerbation occurrence highlight a need for the development and implementation of de-escalation strategies in clinical practice.


Assuntos
Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Dinamarca , Progressão da Doença , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Antagonistas Muscarínicos/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Nephrology (Carlton) ; 24(5): 497-503, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848004

RESUMO

Beta2-adrenergic receptor (ß2 -AR) is a G-protein-coupled adrenergic receptor family member, whose clinical significance has been extensively investigated in lung, cardiovascular and muscular diseases, but its role in kidney biology remains understudied. In this review, we discuss some of the recent studies, where the effect of agonist/antagonist-mediated activation/inhibition of ß2 -AR on disease pathogenesis process was studied, and highlighted the role of ß2 -AR in kidney biology. The expression of ß2 -AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules ß2 -AR is involved in Na-ATPase activity and transcellular Na-transport through protein kinase-C activation; whereas in cultured podocytes, it was associated with depolarization of the membrane. The animal studies further revealed that ß2 -AR activation by short-acting ß2 agonists attenuated monocyte activation, pro-inflammatory and pro-fibrotic responses through ß-arrestin2 dependent NF-kB inactivation in diabetic kidney disease; in contrast, activation by long-acting ß2 agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC-1α dependent mitochondrial biogenesis. In conclusion, the activation of ß2 -AR may present a rapidly developing therapeutic target for renal diseases.


Assuntos
Lesão Renal Aguda/metabolismo , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/patologia , Lesão Renal Aguda/fisiopatologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Fármacos Renais/uso terapêutico , Transdução de Sinais
20.
J Bronchology Interv Pulmonol ; 26(2): 137-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30829895

RESUMO

BACKGROUND: Bronchial thermoplasty (BT) is a novel bronchoscopic therapy for severe uncontrolled asthma unresponsive to standard pharmacological treatments, including inhaled corticosteroids and long-acting beta-2 agonists. Although several studies have shown that BT improves asthma control, the optimal predictors of BT response remain unknown. PATIENTS AND METHODS: We reviewed 10 consecutive asthma patients treated with BT at Kanazawa University Hospital between January 2016 and March 2018 and attempted to identify factors that correlated with a positive BT response. RESULTS: All patients had the most severe persistent asthma according to the 2017 Japanese guidelines for adult asthma and were uncontrolled despite adequate treatments including high-dose inhaled corticosteroids and long-acting beta-2 agonists. Six patients had significant improvement in asthma control evaluated with the Asthma Control Questionnaire-6. Eight patients showed a significant improvement in asthma-specific health-related quality of life evaluated with the Asthma Quality of Life Questionnaire. The number of severe asthma exacerbations decreased in 6 patients. The maintenance dose of oral corticosteroids decreased in 1 patient. There were no severe adverse events related to the procedure. Six patients showed a positive BT response, and all 4 patients with increased cough receptor sensitivity to capsaicin responded to BT. No other factors, including age, smoking status, body mass index, age of asthma onset, disease duration, blood eosinophil count, total serum immunoglobulin E, prebronchodilator forced expiratory volume in 1 second, reversibility to beta-2 agonist, or fractional exhaled nitric oxide, were associated with a positive BT response. CONCLUSION: Increased cough receptor sensitivity to capsaicin may predict a positive BT response.


Assuntos
Asma/cirurgia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Idoso , Asma/tratamento farmacológico , Asma/fisiopatologia , Termoplastia Brônquica , Capsaicina , Tosse/fisiopatologia , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fármacos do Sistema Sensorial
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA