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1.
Am J Respir Crit Care Med ; 203(1): 14-23, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385220

RESUMO

Rationale: Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guidelines, decisions, and policy.Objectives: The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement to clarify the role of observational studies-alongside randomized controlled trials (RCTs)-in informing clinical decisions in pulmonary, critical care, and sleep medicine.Methods: The committee examined the strengths of observational studies assessing causal effects, how they complement RCTs, factors that impact observational study quality, perceptions of observational research, and, finally, the practicalities of incorporating observational research into ATS clinical practice guidelines.Measurements and Main Results: There are strengths and weakness of observational studies as well as RCTs. Observational studies can provide evidence in representative and diverse patient populations. Quality observational studies should be sought in the development of ATS clinical practice guidelines, and medical decision-making in general, when 1) no RCTs are identified or RCTs are appraised as being of low- or very low-quality (replacement); 2) RCTs are of moderate quality because of indirectness, imprecision, or inconsistency, and observational studies mitigate the reason that RCT evidence was downgraded (complementary); or 3) RCTs do not provide evidence for outcomes that a guideline committee considers essential for decision-making (e.g., rare or long-term outcomes; "sequential").Conclusions: Observational studies should be considered in developing clinical practice guidelines and in making clinical decisions.


Assuntos
Pesquisa Biomédica/normas , Tomada de Decisão Clínica , Cuidados Críticos/normas , Assistência à Saúde/normas , Medicina Baseada em Evidências/normas , Estudos Observacionais como Assunto/normas , Doenças Torácicas/terapia , Humanos , Guias de Prática Clínica como Assunto , Sociedades Médicas , Estados Unidos
2.
Neurol Neurochir Pol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433902

RESUMO

AIM OF THE STUDY: SPACE, a prospective, non-interventional, open-label, multinational study, investigated physicians' and subjects' assessment of safety, efficacy, and health-related quality of life (HRQoL) following botulinum neurotoxin type A (BoNT-A) treatment to understand real-world clinical usage for the management of focal and multifocal spasticity. CLINICAL RATIONALE FOR THE STUDY: Treatment guidelines recommend the use of BoNT-A for the management of spasticity in adults. This study assessed how physicians use BoNT-A therapy in real-world clinical practice, and provided evidence on long-term safety and efficacy over a period of up to 2 years. MATERIALS AND METHODS: BoNT treatment-naïve adults with spasticity of any aetiology received any BoNT-A formulation at their physician's discretion, and were observed for ≤ 8 treatment cycles (≤ 2 years). Daily practice information, physician's global assessments of tolerability and efficacy, and HRQoL were documented. Incidences of adverse drug reactions or all adverse events were documented for non-Mexican subjects and for Mexican subjects, respectively, due to protocol differences based on local regulatory requirements. RESULTS: A total of 701 subjects were enrolled (safety population; nine countries). Physicians rated the tolerability of BoNT-A as 'very good' or 'good' for 88.2-97.4% of subjects throughout the study (subject numbers declined throughout this non-interventional study). Adverse drug reactions were reported for 16/600 (2.7%) of the non-Mexican subjects, with two considered to be 'definitely related' to treatment (injection-site haematoma, n = 1; botulism, n = 1). For 687 subjects, efficacy was rated 'very good' or 'good' by most physicians and subjects. Improvements in HRQoL were observed. CONCLUSIONS AND CLINICAL IMPLICATIONS: Throughout this 2-year study, BoNT-A treatment was generally well-tolerated, effective, and associated with an improved HRQoL. This study makes a valuable contribution to the broader understanding of how physicians use BoNT-A therapy to manage spasticity in real-world clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33500616

RESUMO

Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug-drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The AerosphereTM inhaler, formulated using co-suspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery.

4.
Respir Res ; 22(1): 25, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478491

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated. METHOD: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK. RESULTS: A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/µL. CONCLUSIONS: In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Retirada de Medicamento Baseada em Segurança/tendências , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Resultado do Tratamento , Reino Unido/epidemiologia
5.
J Asthma ; : 1-10, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33493074

RESUMO

Objective: In asthma, treatment effectiveness is strongly influenced by the quality of inhaler use. New devices such as Spiromax® have been specifically developed to improve ease of use. It is crucial to determine whether switching to such a device improves inhaler technique and clinical outcomes, and to identify factors associated with handling errors. Methods: This observational study assessed inhaler device handling errors in 1435 asthma patients recruited via 135 participating physicians in France, before and after switching therapy from the Symbicort Turbuhaler® or Seretide® Diskus® to DuoResp® Spiromax®. Patients received training in the use of their new device at baseline and were re-assessed after three months. Results: After three months of use, 67% of patients were using the DuoResp® Spiromax® with no handling errors, and 88% with no critical errors. The presence of comorbidities was associated with handling errors overall. Concurrent illness potentially affecting device handling and previous training were associated with critical device handling errors. Most patients (85.4%) preferred DuoResp® Spiromax® over their previous device. Levels of inadequately controlled or uncontrolled asthma were reduced from baseline among patients using DuoResp® Spiromax® (8.6% versus 64.6%), and were higher in patients with critical handling errors. Conclusions: Effective patient education, correct inhaler technique, treatment adherence and devices associated with high patient satisfaction are interrelated factors key to the successful delivery of inhaled asthma therapy. Inhaler technique and patient device satisfaction should be routinely assessed in treated patients with uncontrolled asthma. Supplemental data for this article can be accessed at publisher's website.

6.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33263033

RESUMO

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system.

7.
Int J Chron Obstruct Pulmon Dis ; 15: 2739-2750, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149571

RESUMO

Purpose: This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations. Patients and Methods: A historical cohort study was conducted using data from the UK's Optimum Patient Care Research Database. Patients with COPD ≥40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated. Results: A total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV1 <80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94-1.09]), acute respiratory events (IRR = 0.98 [0.92-1.04]), acute OCS courses (IRR = 1.01 [0.91-1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90-1.09]), but not for mMRC (OR = 0.93 [0.69-1.27]) or risk of pneumonia (HR = 0.50 [0.14-1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness. Conclusion: This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.

8.
Ann Phys Rehabil Med ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33152520

RESUMO

BACKGROUND: Botulinum toxin injection (BTI) reduces muscle hyperactivity but its effect on active upper limb function is limited. Intensive rehabilitation could optimize the effects; however, outpatient post-stroke rehabilitation is usually not intensive. One solution could be self-rehabilitation. OBJECTIVES: The aim of this randomized controlled trial was to determine the effects of a self-rehabilitation program combined with BTI on upper limb function in individuals with chronic hemiparesis. METHODS: Thirty-three outpatients were randomly allocated to receive either BTI + self-rehabilitation (R group: n=17) or BTI alone (C group: n=16). Outcomes evaluated just before the BTI and 4 weeks later included: Wolf Motor Function Test (WMFT time - Primary Outcome), Action Research Arm Test, fatigue and quality of life. RESULTS: Change in WMFT was not different between groups at 4 weeks (WMFT time: -14% for R group, -4 % for C group. WFMT score: +12 % for R group, 0 % in C group). WFMT time and score improved significantly (-14 %, p=0.01 and +12 %, p=0.02 respectively) in the R group only. In addition, the proportion of patients with improved WMFT time and scores was higher in the R group (71% improved score, 77% improved time, C group 43% improved score, 50% improved time). Passive range of shoulder flexion (p=0.03) and wrist extension (p=0.01) also improved only in the R group. No other variables changed significantly. Compliance was excellent; average daily training time was greater than that prescribed. CONCLUSIONS: The addition of a self-rehabilitation program to BTI did not significantly improve functional outcomes more than BTI alone, however movement quality and speed only improved in the self-rehabilitation group. Participants in the self-rehabilitation group trained more than they were asked to, suggesting they found the program worthwhile. These clinically relevant findings justify larger-scale studies into the effects of self-rehabilitation to enhance the effects of BTI.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33211970

RESUMO

Currently the diagnosis of chronic obstructive pulmonary disease (COPD) requires the demonstration of airflow limitation, defined as a post-bronchodilator FEV1/FVC <0.7, a measurement that remains methodologically robust and widely available. FEV1 is one of the most powerful predictors of clinically relevant outcomes including symptoms, exacerbations and mortality. However, reliable data suggest that respiratory symptoms, in particular chronic bronchitis, airway abnormality and emphysema detected using modern imaging techniques such as computed tomography (CT), and certain physiologic measures including rapid decline in FEV1 and DLCO are present among individuals who do not meet spirometric criteria for COPD. These abnormalities may help to identify individuals at increased risk for developing airflow limitation in the future. Here, we review the evidence that support the use of the term "pre-COPD" in individuals with symptoms (e.g., "Non-Obstructive Chronic Bronchitis" (NOCB)), physiologic (e.g., low DLCO) and/or imaging abnormalities (e.g. CT emphysema) but spirometry in the normal range, who are at risk of developing COPD defined by a reduced FEV1/FVC ratio. We acknowledge, however, that further research on early disease in young individuals will be critical to develop a clinically operable definition of "pre-COPD" that demonstrates good sensitivity and specificity. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

11.
J Appl Physiol (1985) ; 129(6): 1257-1266, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002379

RESUMO

Chronic obstructive pulmonary disease (COPD) in never-smokers exposed to organic dusts is still poorly characterized. Therapeutic strategies in COPD are only evaluated in smoking-related COPD. Understanding how never-smokers with COPD behave during exercise is an important prerequisite for optimal management. The objective of this study was to compare physiological parameters measured during exercise between never-smokers with COPD exposed to organic dusts and patients with smoking-related COPD matched for age, sex, and severity of airway obstruction. Healthy control subjects were also studied. Dyspnea (Borg scale), exercise tolerance, and ventilatory constraints were assessed during incremental cycle cardiopulmonary exercise testing in COPD patients at mild to moderate stages [22 exposed to organic dusts: postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z score -2.44 ± 0.72 and FEV1 z score -1.45 ± 0.78; 22 with smoking-related COPD: FEV1/FVC z score -2.45 ± 0.61 and FEV1 z score -1.43 ± 0.69] and 44 healthy control subjects (including 22 never-smokers). Despite the occurrence of similar significant dynamic hyperinflation, never-smoker COPD patients exposed to organic dusts had lower dyspnea ratings than those with smoking-related COPD. They also had better ventilatory efficiency, higher peak oxygen consumption and peak power output than smoking-related COPD patients, all these parameters being similar to control subjects. Differences in exercise capacity between the two COPD groups were mainly driven by better ventilatory efficiency stemming from preserved diffusion capacity. Never-smokers exposed to organic dusts with mild to moderate COPD have better exercise capacities, better ventilatory efficiency, and better diffusion capacity than matched patients with smoking-related COPD.NEW & NOTEWORTHY It is unknown whether or not never-smokers with chronic obstructive pulmonary disease (COPD) behave like their smoking counterparts during exercise. This is the first study showing that never-smokers with mild to moderate COPD [defined by a postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < lower limit of normal] have preserved exercise capacities. They also have lower exertional dyspnea than patients with smoking-related COPD. This suggests that the two COPD groups should not be managed in the same way.

13.
Environ Res ; 188: 109847, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32846639

RESUMO

BACKGROUND: Although farming is often considered a risk factor for COPD, data regarding the burden and characteristics of COPD in dairy farmers are sparse and conflicting. OBJECTIVES: To characterize COPD in dairy farmers. METHODS: 4788 subjects entered two parallel COPD screening programs, one in agricultural workers and one in general practice from 2011 to 2015. Subjects with COPD were invited to participate in the characterization phase of the study. Those who accepted were included in two subgroups: dairy farmers with COPD (DF-COPD) (n = 101) and non-farmers with COPD (NF-COPD) (n = 85). Patients with COPD were frequency-matched with subjects with normal spirometry for age, sex and tobacco smoking (pack-years and status) (DF-controls n = 98, NF-controls n = 89). All subjects from these four groups underwent lung function and exercise testing, questionnaires and blood analysis. RESULTS: The frequency of COPD in dairy farmers was 8.0% using the GOLD criterion and 6.2% using the lower limit of normal criterion and was similar in non-farming subjects (7.3% and 5.2%, respectively) although dairy farmers had lower tobacco consumption (screening phase). DF-COPD had better pulmonary function, exercise capacity and quality of life, fewer symptoms and comorbidities than NF-COPD, and higher levels of some Th2 biomarkers (MCP-2, periostin) (characterization phase). In farmers, COPD was not related to occupational exposure factors, supporting the role of host factors. CONCLUSION: COPD secondary to organic dust exposure (dairy farming) appears less severe and associated with fewer comorbidities than COPD secondary to tobacco smoking.


Assuntos
Exposição Ocupacional , Doença Pulmonar Obstrutiva Crônica , Indústria de Laticínios , Fazendeiros , Humanos , Exposição Ocupacional/efeitos adversos , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Qualidade de Vida , Fatores de Risco , Espirometria
14.
Respir Med ; 171: 106105, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32858497

RESUMO

BACKGROUND: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females. METHODS: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis. RESULTS: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV1%, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69-1.96) and 1.73 (1.50-2.00), respectively. CONCLUSIONS: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients.

15.
Clin Chest Med ; 41(3): 485-494, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800201

RESUMO

Inhaled therapy remains the cornerstone of chronic obstructive pulmonary disease pharmacologic care, but some systemic treatments can be of help when the burden of the disease remains high. Azithromycin, phosphodiesterase-4 inhibitors, and mucoactive agents can be used in such situations. The major difficulty remains in the identification of the optimal target populations. Another difficulty is to determine how these treatments should be positioned in the global treatment algorithm. For instance, should they be prescribed in addition to other antiinflammatory agents or should they replace them in some cases? Research is ongoing to identify new therapeutic targets.


Assuntos
Anti-Inflamatórios/uso terapêutico , Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Broncodilatadores/farmacologia , Humanos
16.
Science ; 369(6504): 718-724, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32661059

RESUMO

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-ß and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Interferon alfa-2/metabolismo , Interferon-alfa/metabolismo , Interferon beta/metabolismo , Pneumonia Viral/imunologia , Adulto , Idoso , Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Estado Terminal , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Inflamação , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Pandemias , Pneumonia Viral/virologia , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral
17.
BMJ Open ; 10(7): e035811, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611741

RESUMO

OBJECTIVES: Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. DESIGN: A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results. SETTING: COPD exacerbation management in France. PARTICIPANTS: 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. RESULTS: 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. CONCLUSIONS: This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients. STUDY REGISTRATION: The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.

18.
Int J Chron Obstruct Pulmon Dis ; 15: 1545-1555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669840

RESUMO

Background: Comorbidities including cardiovascular diseases are very common in chronic obstructive pulmonary disease (COPD) secondary to tobacco smoking and contribute to the overall severity of the disease. In non-smoking COPD, which accounts for about 25% of COPD cases worldwide, current knowledge on the frequency and determinants of comorbidities remains scarce. The aims of the current study were to assess the frequency of major comorbidities and to evaluate their determinants in a group of non-selected patients with mild-to-moderate COPD who were exposed to organic dust (dairy farmers), to tobacco smoking, or to both, and in controls without COPD who were exposed to organic dust (dairy farmers), or to tobacco smoking, or to both, or who were without exposure. Patients and Methods: A total of 4665 subjects (2323 dairy farmers and 2342 non-farmers) including 355 patients with COPD and 4310 controls with normal spirometry were recruited through a large COPD screening program. Self-reported physician-diagnosed diseases with plausible links to COPD were recorded in this cross-sectional study. Results: Whatever the exposure, cardiovascular comorbidities were not more frequent in patients with COPD than their counterparts without airflow limitation. A higher risk of major cardiovascular comorbidities was associated with tobacco smoking and a lower risk was associated with exposure to organic dusts. Conclusion: Tobacco smoking (but not COPD) is associated with higher frequency of cardiovascular comorbidities. By contrast, being a dairy farmer exposed to organic dusts is associated with a lower frequency of the same comorbidities. This reinforces the crucial need for controlling established cardiovascular risk factors even in patients with mild-to-moderate COPD.

19.
Eur J Pharm Sci ; 153: 105472, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682074

RESUMO

This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 µg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 µg per actuation) radiolabelled with 99mTc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.

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