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1.
Rev Med Suisse ; 17(749): 1515-1519, 2021 Sep 08.
Artigo em Francês | MEDLINE | ID: mdl-34495587

RESUMO

Inhaled medication is the cornerstone of medical treatment of COPD. The efficacy of these treatments depends on the optimal use of inhalation devices. This requires not only an impeccable inhalation technique, but above all the selection of an inhaler adapted to the patient. In this article, we describe the specificities of the different inhalation devices and some of the patient's characteristics to be taken into account when selecting an inhaler, in particular the presence of cognitive disorders, impaired dexterity or insufficient inspiratory force.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Aerossóis/uso terapêutico , Desenho de Equipamento , Humanos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
2.
BMC Pulm Med ; 21(1): 278, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465321

RESUMO

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report. CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive. CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Diagnóstico Tardio , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Administração por Inalação , Corticosteroides/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Asma/patologia , Lavagem Broncoalveolar , COVID-19/complicações , COVID-19/terapia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502019

RESUMO

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Pulmão/patologia , Fator de Crescimento Neural/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/patologia , COVID-19/tratamento farmacológico , COVID-19/patologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/métodos , Fator de Crescimento Neural/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia
4.
Int J Chron Obstruct Pulmon Dis ; 16: 2397-2406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465987

RESUMO

Background: Beta-blockers have been proposed to improve COPD-related outcomes, yet studies report conflicting results. We aimed to investigate the effect of beta blockers on time-to-first exacerbation and all-cause mortality in high-risk COPD outpatients. Methods: All COPD outpatients managed at the Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Denmark in 2016 were followed for 3.5 years in this retrospective, registry-based cohort study. Outcomes were time-to-first acute exacerbation of COPD (AECOPD) or death. The association was estimated using time-varying crude and multivariable Cox proportional hazard regression adjusted for age, sex, BMI, use of COPD medication, smoking status, cardiovascular disease and COPD severity. Results: The cohort comprised 950 COPD outpatients, mean age 71 (SD 11) years, and FEV1 44% predicted (IQR 33%; 57%). The annual exacerbation rate was 0.88 (SD 1.68) and 211 patients (22%) had a history of hospitalization requiring AECOPD within 12 months. Of the enrolled patients, 247 (26%) were prescribed beta blockers. Beta-blocker use was associated, although with borderline significance, with increased all-cause mortality (HR 1.37 (95% CI, 0.99 to 1.89, p = 0.059)). On the other hand, beta blocker use did not reduce the risk of AECOPD (HR = 0.89 (95% CI 0.71 to 1.10; p = 0.270)), which remained non-significant after stratifying for severity of exacerbations. Conclusion: We found an association between beta blocker use and all-cause mortality in high-risk COPD outpatients. No association was found between beta blocker use and risk of AECOPD.


Assuntos
Pacientes Ambulatoriais , Doença Pulmonar Obstrutiva Crônica , Idoso , Estudos de Coortes , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
5.
Int J Chron Obstruct Pulmon Dis ; 16: 2407-2417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465988

RESUMO

Background: Recent studies evaluating the predictive value of different variables on future exacerbations suggest exacerbation history as the strongest predictor. We examined the effect of exacerbation history on subsequent events in a large sample population with over 250,000 COPD patients using up to 8 years of longitudinal healthcare data from Germany. Methods: Patients 40 years or older with any COPD diagnosis in primary or secondary care were included from 2011 to 2017 (index period) from healthcare insurance claims (Germany; WIG2 research database), with 12 months before index date as baseline and at least 12-month follow-up. Exacerbations during baseline were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization). Results: Patients without (category A), with one moderate (category B), or with either one severe or several baseline exacerbations (category C) experienced an average of 0.9 (CI 0.9-0.9), 1.9 (CI 1.9-1.9), and 6.3 (CI 6.1-6.3) exacerbations during the first 3 years of follow-up, respectively. By 8 years, 87.0% (CI 86.6-87.4), 70.5% (CI 69.9-71.0) and 49.1% (CI 48.9-49.3) of category C, B and A patients had experienced a subsequent exacerbation. Conclusion: Baseline exacerbations increased the likelihood of, and reduced time to subsequent exacerbations. Even patients without baseline exacerbations experienced exacerbations within three years, emphasizing the importance of adequate treatment in patients with less severe disease presentation as well.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Progressão da Doença , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos
6.
Int J Chron Obstruct Pulmon Dis ; 16: 2433-2443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465989

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is mainly caused by smoking, and most patients with COPD are either former or current smokers. The optimal way to slow down disease progression and reduce overall mortality is for patients to stop smoking. Patients with COPD are known to have lower socio-economic status and to be more nicotine-dependent than most other smokers and therefore face difficulties when attempting to quit smoking. Pharmacological smoking cessation treatment is known to be the most effective. However, the extent to which this treatment is actually offered to Danish smokers with COPD is unknown. Aim: The aim of this study was to investigate if patients with COPD were more likely to redeem a prescription for smoking cessation medication compared with matched controls. Materials and Methods: The study was designed as a registry-based, non-interventional case-control study. All Danish patients with COPD (ICD-10-code J 44 chronic obstructive pulmonary disease) diagnosed between 2009 and 2015 were included (130,797 cases). Controls (252,216) were matched on age, gender and geography. Primary outcome was the number of redeemed prescriptions for smoking cessation medication. Results: We found that 12% of patients with COPD redeemed a prescription for smoking cessation medication during the eight-year study period. The odds ratio (OR) for redeeming a prescription on smoking cessation medicine was OR 6.22 for patients with COPD compared with their matched controls. We also found that patients with COPD were more likely to redeem smoking cessation medication if they were younger, female or single. Conclusion: There is substantial room for improvement with respect to pharmacological smoking cessation treatment in Danish patients with COPD. In-depth knowledge of factors contributing to the patients choice of smoking cessation treatment might allow for more personalized guidance of patients with COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Abandono do Hábito de Fumar , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Dispositivos para o Abandono do Uso de Tabaco , Vareniclina
7.
Int J Chron Obstruct Pulmon Dis ; 16: 2419-2431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471349

RESUMO

Background: Clinicians' selection of glucocorticoids during hospitalization of COPD patients is often based on the medical staff's judgment of the patient's condition, and there is no objective judgment standard. The purpose of this study was to investigate the outcome of severe COPD deterioration in patients treated with glucocorticoid and without glucocorticoid during hospitalization. Methods: This study was an observational cohort study. Data on hospitalization with severe COPD deterioration were collected and followed up for 1 year. One year after discharge, the re-hospitalization due to COPD was collected retrospectively. The patients were divided into glucocorticoid group and control group according to whether the patients were given glucocorticoid therapy or not when they were admitted to hospital for the first time. The primary outcome was rate of future COPD exacerbations, while the secondary outcome was hospital stay, treatment cost and COPD-related readmission time. These results are analyzed by using Poisson model and Cox regression model. Results: A total of 91 patients were enrolled in the study, including 39 in the control group and 52 in the glucocorticoid group. The annual rate of future COPD exacerbations in the glucocorticoid group was significantly lower than that in the control group (RR,0.50 [95% CI, 0.26-0.98]; P = 0.045). The risk of COPD recurrence in the glucocorticoid group was lower than that in the control group, as assessed in a time-to-first-event analysis (HR,0.46[95% CI 0.22-0.97]; P = 0.042). Subgroup analysis found that in patients with blood eosinophil <100 cells/µ l, the future annual severe exacerbation rate of glucocorticoid group was significantly lower than that in the control group (adjusted RR,0.37 [95% CI 0.17-0.83]; P = 0.016). Conclusion: The use of glucocorticoids during hospitalization in COPD can more effectively reduce the severe deterioration of COPD than without glucocorticoids.


Assuntos
Glucocorticoides , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Eosinófilos , Glucocorticoides/efeitos adversos , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos
8.
Adv Ther ; 38(9): 4815-4835, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34347255

RESUMO

INTRODUCTION: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD. METHODS: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening. RESULTS: The analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV1 at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: - 0.42 [- 0.63, - 0.20]; former: - 0.25 - 0.44, - 0.05]) and salmeterol (current: - 0.28 [- 0.49, - 0.06]; former: - 0.29 [- 0.49, - 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups. CONCLUSIONS: In current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Fumantes , Administração por Inalação , Álcoois Benzílicos , Broncodilatadores/uso terapêutico , Clorobenzenos/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/uso terapêutico , Resultado do Tratamento
9.
Adv Ther ; 38(9): 4847-4858, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34357561

RESUMO

INTRODUCTION: The Salford Lung Studies (SLS) were real-world randomised controlled trials set within UK primary care that assessed the effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol versus continuing usual care in patients with chronic obstructive pulmonary disease or asthma. Data were collected for a relatively short period, limiting the study of long-term outcomes. To broaden the capture of SLS patients' data, we undertook the Extended SLS (Ext-SLS), aiming to better understand the patient disease journey and the effects of treatment in a real-world setting, through collection of patient-level data. Here, we present study design information and the challenges and learnings gathered in creating the Ext-SLS. METHODS: The Ext-SLS was intended to augment the SLS by collecting retrospective and prospective (up to 10 years from consent) primary and secondary care electronic health record (EHR) data and patient questionnaires. After ethics approval, general practitioners (GPs) obtained consent from SLS patients remotely (mean 3.2 years post-SLS completion). To facilitate GPs identifying eligible patients, a novel EHR-based approach flagged SLS patients who were alive and registered with their original GP. An automated system sent consent forms/questionnaires to patients. Medical data were collected via EHRs; primary care data were extracted from GPs' systems whilst secondary care data were sourced from the UK NHS. RESULTS: Of the 75 GP sites from the SLS, 35 (47%) declined Ext-SLS participation leaving 4158 potentially eligible patients; 1169 (28%) patients were excluded as GPs could not confirm them as SLS participants or due to incapacity. Of 2989 patients invited, 1189 (40%) consented. CONCLUSIONS: Developing an EHR-based trial extension was achieved, with reasonable consent rates amongst invited patients. The resulting Ext-SLS is a unique and valuable research resource. Leveraging EHRs and technology reduced GP burden, facilitating participation. Initiation of extension studies prior to study close-out may help increase GP and patient participation.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Corrida , Humanos , Pulmão , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
10.
Int J Chron Obstruct Pulmon Dis ; 16: 2227-2242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354348

RESUMO

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition affecting 10% of the global population over 45 years. Currently, there are no disease-modifying treatments, with current therapies treating only the symptoms of the disease. COPD is an inflammatory disease, with a high infiltration of leukocytes being found within the lung of COPD patients. These leukocytes, if not kept in check, damage the lung, leading to the pathophysiology associated with the disease. In this review, we focus on the main leukocytes found within the COPD lung, describing how the release of chemokines from the damaged epithelial lining recruits these cells into the lung. Once present, these cells become active and may be driven towards a more pro-inflammatory phenotype. These cells release their own subtypes of inflammatory mediators, growth factors and proteases which can all lead to airway remodeling, mucus hypersecretion and emphysema. Finally, we describe some of the current therapies and potential new targets that could be utilized to target aberrant leukocyte function in the COPD lung. Here, we focus on old therapies such as statins and corticosteroids, but also look at the emerging field of biologics describing those which have been tested in COPD already and potential new monoclonal antibodies which are under review.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Remodelação das Vias Aéreas , Humanos , Leucócitos , Pulmão , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/tratamento farmacológico
11.
BMJ Open ; 11(8): e049675, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348953

RESUMO

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting ß2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands. METHODS: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively. RESULTS: Treatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer's incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries. CONCLUSIONS: Based on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Finlândia , Humanos , Países Baixos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Suécia , Brometo de Tiotrópio/uso terapêutico , Resultado do Tratamento
12.
BMJ Open ; 11(8): e049515, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353802

RESUMO

INTRODUCTION: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate. METHODS AND ANALYSIS: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission. ETHICS AND DISSEMINATION: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04682899.


Assuntos
Infecções Bacterianas , Doença Pulmonar Obstrutiva Crônica , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Humanos , Pacientes Internados , Estudos Multicêntricos como Assunto , Pró-Calcitonina , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Indian J Med Res ; 153(4): 465-474, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34380793

RESUMO

Background & objectives: Upregulation of matrix metalloproteinases (MMPs) is related to the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed at assessing the tolerability and impact of long-term use of MMP inhibitor doxycycline in COPD. Methods: A cohort of COPD patients was randomized to continue a uniform COPD treatment with or without add-on long-term oral doxycycline. The lung exacerbations (spirometry), adverse events and health status (COPD Assessment Test score) were noted at 3, 6, 9 and 12 months of therapy. Measurement of the serum MMP-2, and 9 and high-sensitive C-reactive protein (hs-CRP) levels was done at the start of the study and at three months, whenever possible. Results: There were 27, 19, 13 and 10 patients with add-on doxycycline group and 22, 19, 11 and 7 patients with COPD treatment alone at 3, 6, 9 and 12 months of treatment respectively. The improvement was obvious and mostly (at 6 and 12 months) significant (P >0.05) for lung function parameters [forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF25-75)] and universal for health status at all measurements, with an overall 26.69 per cent reduction in exacerbations. The analysis with the lung function changes in the available population with protocol violation also supported the same trend. The concomitant reduction in serum MMP-9 (P =0.01), MMP-2 (P =0.01) and hs-CRP (P =0.0001) levels (n=21) at three months was also significant. The adverse reactions with add-on doxycycline appeared acceptable. Interpretation & conclusions: Long-term doxycycline appears well tolerated and seems to improve lung function, health status and exacerbations in COPD. The claim needs further scientific validations.


Assuntos
Doxiciclina , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Doxiciclina/efeitos adversos , Volume Expiratório Forçado , Humanos , Pulmão , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Capacidade Vital
14.
Biomed Khim ; 67(4): 352-359, 2021 Jul.
Artigo em Russo | MEDLINE | ID: mdl-34414894

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterized by reduced sensitivity of cells to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin and a low dose theophylline have a significant impact on molecular mechanisms leading to corticosteroid resistance. The aim of this study was to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of GCs on the production of cytokines by NK and NKT-like blood cells of COPD patients. Whole blood cells from COPD patients (n=21) were incubated in the presence of budesonide (10 nM), azithromycin (10 µg/mL), theophylline (1 µM), or their combinations and stimulated with phorbol myristate acetate (50 ng/mL). Intracellular production of proinflammatory cytokines in NK (CD3-CD56+) and NKT-like (CD3+CD56+) blood cells was analyzed by flow cytometry. Budesonide reduced synthesis of interleukin 4 (IL-4), CXCL8, tumor necrosis factor α (TNFα) by NK and NKT-like cells, as well as production of interferon γ (IFNγ) by NK cells. Azithromycin suppressed production of IL-4 and CXCL8 by NK and NKT-like cells, and theophylline inhibited IL-4 synthesis by these lymphocytes. The combination of azithromycin and budesonide had a more pronounced inhibitory effect on the production of IL-4 and CXCL8 by NK and NKT-like cells than the effect of these drugs alone. The combination of theophylline and budesonide suppressed synthesis of IL-4 and CXCL8 by NK and NKT-like cells, as well as the production of TNFα and IFNγ by NK cells stronger than budesonide alone. The obtained results demonstrate the benefits for the combined use of GCs with theophylline at a low dose or azithromycin to suppress the inflammatory process in patients with COPD.


Assuntos
Glucocorticoides , Doença Pulmonar Obstrutiva Crônica , Azitromicina/farmacologia , Citocinas , Humanos , Células Matadoras Naturais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/farmacologia
15.
Rev Assoc Med Bras (1992) ; 67Suppl 1(Suppl 1): 97-101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34406300

RESUMO

OBJECTIVE: Failure to achieve high levels of medication adherence in obstructive lung diseases is a major cause of uncontrolled disease. The purpose of this study is to reveal clinicians' opinions on the level of patient adherence and the change in adherence during the COVID-19 pandemic. METHODS: A questionnaire containing multiple-choice questions about treatment adherence in patients with obstructive lung diseases was voluntarily applied to doctors working in a tertiary hospital for chest diseases. RESULTS: Eighty-one doctors (mean age, 37.2 years [standard deviation, 9.7 years]; 57 (70.4%) women) answered the questionnaires. Almost all clinicians participating in the study reported that they always or frequently asked patients if they adhered to treatment. Most clinicians think that in 20-50% of patients with asthma and less than 20% of patients with chronic obstructive pulmonary disease, a decrease in medication adherence appears in the first year of treatment. Most clinicians think the main reason for patients with obstructive lung diseases not adhering is patients' reluctance to be treated regularly. Regarding the impact of the COVID-19 pandemic on patients' drug adherence, 43.2% of clinicians observed that adherence increased after the start of the pandemic. CONCLUSIONS: Adherence to medication is not at the desired levels in patients with obstructive lung diseases. However, when faced with a serious health threat, such as the COVID-19 pandemic, patients realize the severity of their illness and begin using their treatments more regularly.


Assuntos
COVID-19 , Doença Pulmonar Obstrutiva Crônica , Adulto , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Pandemias , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , SARS-CoV-2
16.
BMJ Open ; 11(8): e053446, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452971

RESUMO

INTRODUCTION: Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (ß)-blockers. There is observational evidence that cardioselective ß-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective ß-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective ß-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity. METHODS AND ANALYSES: This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV1) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months. ETHICS AND DISSEMINATION: The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital. TRIAL REGISTRATION NUMBERS: NCT03917914; CTRI/2020/08/027322.


Assuntos
Bisoprolol , Doença Pulmonar Obstrutiva Crônica , Bisoprolol/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Clin Drug Investig ; 41(9): 785-794, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333742

RESUMO

BACKGROUND AND OBJECTIVE: In asthma, symptom control is a primary goal that is not consistently met with available treatment options. The first commercially available fixed-dose combination in a single inhaler of a long-acting beta-agonist (indacaterol, IND), an inhaled corticosteroid (mometasone furoate, MF) and a long-acting muscarinic antagonist (glycopyrronium, GLY) has shown promising clinical results in phase III trials. The aim of the present study is to evaluate the cost-utility of IND/GLY/MF fixed-dose combination relative to a combination of salmeterol/fluticasone and tiotropium or salmeterol/fluticasone or IND/MF in adult patients with asthma, from the Italian Health Service (NHS) perspective. METHODS: A two-state and 4-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/GLY/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from the literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/GLY/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating the impact of uncertainty on input parameters. RESULTS: IND/GLY/MF is associated with a higher quality of life [+ 0.25 quality-adjusted life-year (QALY)] than salmeterol/fluticasone plus tiotropium, with an incremental cost of -€3213.90. The incremental cost-utility ratio indicates dominance. At a threshold of €5000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.21 QALY) than salmeterol/fluticasone, with an incremental cost of €2547.76. Incremental cost-utility ratio results in €11,897 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.34 QALY) than IND/MF, with an incremental cost of €4745.91. Incremental cost-utility ratio results in €14,088 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. CONCLUSION: The results indicate that IND/GLY/MF is cost effective against the considered comparators in a cohort representative of adult patients with asthma in Italy.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Acetatos/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Combinação de Medicamentos , Glicopirrolato , Humanos , Indanos , Furoato de Mometasona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Quinolonas , Resultado do Tratamento
18.
J Fam Pract ; 70(5): 244-246, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34410915

RESUMO

This RCT provided valuable insights as to whether CRP-guided prescribing could safely reduce antibiotic use during acute COPD exacerbations.


Assuntos
Antibacterianos/farmacologia , Proteína C-Reativa/análise , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Antibacterianos/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue
19.
Int J Chron Obstruct Pulmon Dis ; 16: 2327-2336, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413641

RESUMO

Background: The study investigated if a web-based clinical decision-support system (CDSS) tool would improve general practitioners' (GPs) accuracy of diagnosis and classification of patients with chronic obstructive pulmonary disease (COPD), and whether nonpharmacological and pharmacological treatment would be better aligned with the COPD guidelines. Methods: GPs were randomized to either a single use of the CDSS or continuing standard of care. The clinical recommendations of the CDSS were based on the GOLD guidelines and provided suggestions for treatment and management of COPD. Data were collected digitally from GPs and patients in both groups using a tablet computer. A follow-up questionnaire was sent to the GPs 1 year after the conclusion of the study. Results: A total of 25 GPs (31% women, mean age 41 years) participated, 12 randomized to using the CDSS tool and 13 followed standard of care when assessing their next five to ten COPD patients. In sum, 149 patients with presumed COPD were included (88 CDSS group, 61 standard-of-care group). In the CDSS group, no COPD misdiagnoses occurred, 98% received vaccine recommendations, and all smokers (n=39) received smoking-cessation advice. The standard-of-care group had 23% misdiagnosis (P<0.001), only 67% received vaccine recommendations (P<0.001), and 87% smoking-cessation advice (P=0.022. All told, 31% of patients did not receive medication as recommended according to guidelines, with no significant differences between the groups. GPs rated the CDSS as very useful. Mean usage time was 3 minutes, 26 seconds. A majority (13 of 19, 68%) of the GPs continued using the CDSS after the conclusion of the study. CAT score identified twice as many patients as having more symptoms than the mMRC, indicating the added value of the multi-item questionnaire. Conclusion: Use of the CDSS was associated with preventing misdiagnosis of COPD and improved adherence to recommended nonpharmacological measures, but a single use did not improve pharmacological treatment considerations.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Clínicos Gerais , Doença Pulmonar Obstrutiva Crônica , Erros de Diagnóstico , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Inquéritos e Questionários
20.
Int J Chron Obstruct Pulmon Dis ; 16: 2363-2373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429594

RESUMO

Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids. Azithromycin can contribute to exacerbation prevention. Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators. This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD. The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea. To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre. Experimental preclinical data confirmed these effects in vitro and in animal models. At present, RPL554/ensifentrine is the only agent of this family in clinical development. It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD. Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients. The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect. Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents. However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality.


Assuntos
Inibidores da Fosfodiesterase 4 , Doença Pulmonar Obstrutiva Crônica , Animais , Broncodilatadores/efeitos adversos , Humanos , Inibidores da Fosfodiesterase 3/efeitos adversos , Inibidores da Fosfodiesterase 4/efeitos adversos , Diester Fosfórico Hidrolases/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida
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