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1.
COPD ; : 1-2, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31423849

RESUMO

The diagnosis of chronic obstructive pulmonary disease (COPD), a global health problem, is challenging in resource-constrained settings. Spirometry with an obstructive pattern after the administration of bronchodilators is required for the diagnosis of COPD. Existing COPD treatment guidelines, largely derived from studies performed in populations of cigarette-smokers, recommend pharmacologic interventions with a tendency to include new-and expensive-drugs as first line agents. As the different factors that cause nonsmokers to develop COPD lead to different phenotypes of disease, COPD severity and treatment efficacy cannot be extrapolated to be the same as in the population of smokers. In so doing, current global initiatives may carry risks when trying to over simplify diagnostic approaches and push for standardization of treatment algorithms that are not context-specific. Future work to mitigate the global burden of COPD needs to address the need for new epidemiological data, especially in areas where tobacco use is less prevalent and environmental factors such as domestic air pollution is common.

2.
Respir Res ; 20(1): 166, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340825

RESUMO

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and cardiovascular disease is a major cause of death in COPD. The current literature indicates that changes in cardiovascular risk during pulmonary rehabilitation (assessed using aortic stiffness) are heterogeneous suggesting that there may be sub-groups of patients who do and do not benefit. OBJECTIVES: To investigate the characteristics of COPD patients who do and do not experience aortic stiffness reduction during pulmonary rehabilitation, examine how changes relate to physical activity and exercise capacity, and assess whether changes in aortic stiffness are maintained at 6 weeks following rehabilitation. METHODS: We prospectively measured arterial stiffness (aortic pulse-wave velocity), exercise capacity (Incremental Shuttle Walk Test) and physical activity (daily step count) in 92 COPD patients who started a six week pulmonary rehabilitation programme, 54 of whom completed rehabilitation, and 29 of whom were re-assessed six weeks later. RESULTS: Whilst on average there was no influence of pulmonary rehabilitation on aortic stiffness (pre- vs. post pulse-wave velocity 11.3 vs. 11.1 m/s p = 0.34), 56% patients responded with a significant reduction in aortic stiffness. Change in aortic stiffness (absolute and/or percentage) during rehabilitation was associated with both increased physical activity (rho = - 0.30, p = 0.042) and change in exercise capacity (rho = - 0.32, p = 0.02), but in multivariable analysis most closely with physical activity. 92% of the responders who attended maintained this response six weeks later. CONCLUSION: Elevated aortic stiffness in COPD is potentially modifiable in a subgroup of patients during pulmonary rehabilitation and is associated with increased physical activity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03003208. Registered 26/12/ 2016.

3.
Thorax ; 74(9): 898-905, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273049

RESUMO

In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago.An ECOPD is 'an acute worsening of respiratory symptoms that results in additional therapy'. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment.

6.
J Clin Immunol ; 39(1): 45-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30547383

RESUMO

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

7.
Respir Med ; 145: 206-211, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30509710

RESUMO

INTRODUCTION: Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or "over-reading" is resource intensive and the impact is unclear. OBJECTIVES: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. METHODS: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. RESULTS: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. CONCLUSION: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW.

8.
Eur Respir J ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30464016

RESUMO

Bronchopulmonary Dysplasia(BPD) is a major complication of preterm birth that leads to lifelong respiratory morbidity. The EPICure study has investigated the longitudinal health outcomes of infants born extremely preterm (<26 weeks-gestation). Our aim was to characterise the airway microbiome in young adults born extremely preterm (EP), with and without neonatal BPD, in comparison to matched term-born controls.Induced sputum was collected from 92 young adults age 19 years (51 EP and 41 controls). Typical respiratory pathogens were detected using quantitative-PCR. 16S-rRNA gene sequencing was completed on 74 samples (29 EP with BPD, 9 EP without BPD and 36 controls).The preterm group with BPD had the least diverse bacterial communities. The relative-abundance of Bacteriodetes, particularly Prevotella melaninogenica was significantly lower in the preterm group compared to controls. This decline was balanced by a nonsignificant increase in Firmicutes. Total Prevotella relative-abundance correlated with FEV1 z-score (ρ=0.272; p<0.05). Typical respiratory pathogens loads and prevalence were similar between groups.In conclusion, extremely preterm birth is associated with a significant dysbiosis in airway microbiome in young adulthood regardless of neonatal BPD status. This is characterised by a shift in the community composition away from Bacteriodetes as manifested in a significant drop in Prevotella relative-abundance.

11.
Trials ; 19(1): 571, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340648

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings. METHODS/DESIGN: We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD. DISCUSSION: This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings. TRIAL REGISTRATION: NCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).

12.
Eur Respir Rev ; 27(149)2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30282634

RESUMO

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently occur together and their coexistence is associated with worse outcomes than either condition alone. Pathophysiological links between COPD and CVD include lung hyperinflation, systemic inflammation and COPD exacerbations. COPD treatments may produce beneficial cardiovascular (CV) effects, such as long-acting bronchodilators, which are associated with improvements in arterial stiffness, pulmonary vasoconstriction, and cardiac function. However, data are limited regarding whether these translate into benefits in CV outcomes. Some studies have suggested that treatment with long-acting ß2-agonists and long-acting muscarinic antagonists leads to an increase in the risk of CV events, particularly at treatment initiation, although the safety profile of these agents with prolonged use appears reassuring. Some CV medications may have a beneficial impact on COPD outcomes, but there have been concerns about ß-blocker use leading to bronchospasm in COPD, which may result in patients not receiving guideline-recommended treatment. However, there are few data suggesting harm with these agents and patients should not be denied ß-blockers if required. Clearer recommendations are necessary regarding the identification and management of comorbid CVD in patients with COPD in order to facilitate early intervention and appropriate treatment.

13.
BMJ Open Respir Res ; 5(1): e000276, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018764

RESUMO

Introduction: Chronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George's Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing. Methods: The SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants. Results: In total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p<0.001). The cross-validated c statistic for SGRQ total score predicting COPD was 0.87 (95% CI 0.75 to 1.00). SGRQ total score was associated with COPD severity (forced expiratory volume in 1 s per cent of predicted), with an r coefficient of -0.60 (-0.75, -0.39). SGRQ score was associated with dyspnoea (OR 1.05/point; 1.01, 1.09) and cough (1.07; 1.03, 1.11). Conclusion: Our Luganda language SGRQ accurately distinguishes between COPD-positive and negative community members in rural Uganda. Scores were correlated with COPD severity and were associated with odds of dyspnoea and cough. We find that it can be successfully used as a respiratory questionnaire for obstructed adults in Uganda.

14.
Med Sci (Basel) ; 6(2)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29865214

RESUMO

20% of chronic obstructive pulmonary disease (COPD) patients admitted to hospital because of an 'exacerbation' will have consolidation visible on a chest X-ray. The presence of consolidation is associated with higher mortality. Imperfect definitions of COPD exacerbation and pneumonia, and incomplete and imperfect diagnostic tests, have resulted in a debate about whether these episodes are best thought of as 'exacerbation with consolidation' or 'pneumonia in a person with COPD'. With the current views that exacerbations are not all identical, and that they can be 'phenotyped' to identify episodes with different prognosis and treatment response, perhaps these episodes are best-considered a phenotype of exacerbation. Whatever the terminology, the important clinical message is to recognise that those with consolidation have higher mortality, and likely different responses to treatment.

15.
Am J Respir Crit Care Med ; 198(3): 329-339, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29779416

RESUMO

RATIONALE: There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations. OBJECTIVES: To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD). METHODS: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 µg once daily) or continuation of triple therapy (tiotropium [18 µg] once daily plus combination of salmeterol/fluticasone propionate [50/500 µg] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints. MEASUREMENTS AND MAIN RESULTS: A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of -26 ml (95% confidence interval, -53 to 1 ml) with confidence limits exceeding the noninferiority margin of -50 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with ≥300 blood eosinophils/µl at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups. CONCLUSIONS: In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/µl suggests that these patients are likely to benefit from triple therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).

16.
Artigo em Inglês | MEDLINE | ID: mdl-29551894

RESUMO

Purpose: Inappropriate use of an inhaled corticosteroid (ICS) for COPD has clinical and economic disadvantages. This retrospective analysis of The UK Health Improvement Network (THIN) database identified factors influencing treatment escalation (step-up) from a long-acting muscarinic antagonist (LAMA) to triple therapy (LAMA + long-acting ß-agonist-ICS). Secondary objectives included time to step up from first LAMA prescription, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grouping (2011/2013, 2017), and Medical Research Council (MRC) grade prior to treatment escalation. Materials and methods: Data were included from 14,866 people ≥35 years old with a COPD diagnosis (June 1, 2010-May 10, 2015) and initiated on LAMA monotherapy. The most commonly used LAMA at baseline was tiotropium (92%). Results: Multivariate analysis (10,492 patients) revealed that COPD exacerbations, lower forced expiratory volume in 1 second (FEV1), "asthma", MRC grade, proactive and reactive COPD primary care, elective secondary-care contact, cough, and number of short-acting bronchodilator prescriptions were positively associated with treatment escalation (P<0.05). Being older, a current/ex-smoker, or having increased sputum symptom codes were negatively associated with treatment escalation (P<0.05). Median MRC score was 2 at baseline and 3 prior to treatment escalation. Using the last MRC reading and exacerbation history in the year prior to escalation, GOLD 2017 groupings were A 27.4%, B 37.3%, C 15.3%, and D 20%. In patients with available FEV1 measures, exacerbations, and MRC code (n=1,064), GOLD 2011/2013 groupings were A 20.4%, B 19.2%, C 24.8%, and D 35.6%. Conclusion: While the presence of COPD exacerbations seems to be the main driver for treatment escalation, according to the 2017 GOLD strategy many patients appear to be overtreated, as they would not be recommended for treatment escalation. Reviewing patients' treatment in the light of the new GOLD strategy has the potential to reduce inappropriate use of triple therapy.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/efeitos adversos , Bases de Dados Factuais , Progressão da Doença , Quimioterapia Combinada , Registros Eletrônicos de Saúde , Feminino , Volume Expiratório Forçado , Humanos , Prescrição Inadequada , Pulmão/fisiopatologia , Masculino , Sobremedicalização , Pessoa de Meia-Idade , Análise Multivariada , Antagonistas Muscarínicos/efeitos adversos , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Reino Unido
20.
J Allergy Clin Immunol Pract ; 6(1): 159-168.e3, 2018 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28734862

RESUMO

BACKGROUND: Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated. OBJECTIVES: To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations. METHODS: We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID. RESULTS: There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%. CONCLUSIONS: Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted.

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