RESUMEN
Importance: Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. Objective: To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. Design, Setting, and Participants: The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. Interventions: Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). Main Outcomes and Measures: The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. Results: Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, -0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). Conclusions and Relevance: Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations. Trial Registration: isrctn.org Identifier: ISRCTN27066620.
Asunto(s)
Corticoesteroides/administración & dosificación , Broncodilatadores/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Teofilina/administración & dosificación , Administración por Inhalación , Anciano , Broncodilatadores/efectos adversos , Broncodilatadores/sangre , Método Doble Ciego , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Teofilina/efectos adversos , Teofilina/sangre , Insuficiencia del Tratamiento , Capacidad Vital/efectos de los fármacosAsunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Vitamina D , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2 , Vitamina D/análogos & derivadosRESUMEN
BACKGROUND: Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking. Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression. Unfortunately access to trained CBT therapists is limited. The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population. In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described. METHODS/DESIGN: This is a prospective open randomised controlled trial comparing CBT with self-help leaflets. The primary outcome measure is the Hospital Anxiety & Depression Scale (HADS) - anxiety subscale. Secondary outcome measures include disease specific quality of life COPD Assessment Tool (CAT), generic quality of life (EQ5D) and HADS-depression subscale. Patients will be followed up at three, six and 12 months following randomisation. DISCUSSION: This is the first randomised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses. Recruitment has commenced and should be complete by February 2014. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN55206395.
Asunto(s)
Ansiedad/psicología , Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Enfermeras y Enfermeros , Enfermedad Pulmonar Obstructiva Crónica/psicología , Neumología , Estudios de Seguimiento , Humanos , Pruebas de Inteligencia , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Calidad de Vida , Tasa de Supervivencia , Resultado del Tratamiento , Reino UnidoRESUMEN
Introduction: Patients with COPD who exhibit elevated levels of anxiety and/or depression are typically less able to improve symptoms and physical activity levels following a programme of pulmonary rehabilitation (PR). The objective of the present study was to provide proof of concept that offering an intervention comprising cognitive behavioural therapy (CBT) alongside physical activity behavioural modification strategies (BPA) during PR is more effective in improving physical activity outcomes compared to PR and CBT alone. Methods: 32 patients with COPD (mean±sd forced expiratory volume in 1â s 42±14% predicted) were assigned 1:1 to receive PR+CBT+BPA or PR+CBT. BPA comprised motivational interviews, step-count monitoring, feedback using a pedometer and goal setting. Assessments included accelerometer-derived steps per day, movement intensity, 6-min walk distance (6MWD) and Hospital Anxiety and Depression Scale (HADS) scores. Results: The magnitude of improvement across physical activity outcomes was greater for the PR+CBT+BPA compared to the PR+CBT intervention (by 829 steps per day (p=0.029) and by 80±39 vector magnitude units (p=0.042), respectively). Compared to PR and CBT alone, the PR+CBT+BPA intervention induced greater clinically meaningful improvements in HADS anxiety scores (by -2â units, 95% CI -4-1â units) and 6MWD (by 33±20â m). Conclusions: Providing anxious and/or depressed patients with COPD with a combined intervention of CBT and BPA during PR presents more favourable improvements in physical activity outcome measures compared to CBT alone during PR.
RESUMEN
BACKGROUND: Multiple factors contribute to muscle weakness and reduced muscle mass in chronic obstructive pulmonary disease (COPD) and this impacts patients' quality of life. One factor implicated in this process is systemic inflammation, an accompaniment of acute exacerbations. Recurrent exacerbations are associated with lower health status. This study examines the relationship between muscle weaknesses, health status and exacerbation frequency in a cohort of patients with COPD. METHODS: This is an observational study of 188 (95 female) patients with COPD attending two hospital clinics in the northeast of England between 2004 and 2007. We measured spirometry, body mass index, health status (St George's Respiratory Questionnaire) and grip strength and recorded Medical Research Council dyspnoea scores and the frequency of exacerbations in the previous year. RESULTS: Patients were aged 72.5±8.3 years (data expressed as mean±SD) with Medical Research Council score of 3.6±0.8, forced expiratory volume in one second (FEV(1)) of 49.2±21.5 per cent predicted and a total St George's Respiratory Questionnaire score of 72.2±15.5. Grip strength, expressed as per cent predicted, was 72.0±21.8 in men and 81.0±18.2 in women. Exacerbations ranged from zero to five in the previous year and there were associations of reduced grip strength with exacerbation frequency (χ(2)=9.634; p=0.0019) and lower health status (χ(2)=34.00; p<0.001). CONCLUSION: Our data clearly demonstrate that reduction in grip strength occurs more frequently and to a greater extent in patients with a history of frequent exacerbations and is associated with reduced health status.
Asunto(s)
Progresión de la Enfermedad , Disnea/diagnóstico , Fuerza de la Mano , Debilidad Muscular/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Anciano , Estudios de Cohortes , Disnea/etiología , Disnea/fisiopatología , Inglaterra , Femenino , Volumen Espiratorio Forzado , Estado de Salud , Humanos , Masculino , Debilidad Muscular/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Espirometría , Encuestas y Cuestionarios , Capacidad VitalRESUMEN
We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.
Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Neoplasias Pulmonares , Tuberculosis Pulmonar , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antituberculosos/uso terapéutico , Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Disección del Cuello , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Radioterapia , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/patología , GemcitabinaRESUMEN
AIMS AND OBJECTIVES: The Clinical PROactive Physical Activity in COPD (C-PPAC) instrument, combines a questionnaire assessing the domains of amount and difficulty of physical activity (PA) with activity monitor data (steps/day and vector magnitude units) to assess patients' experiences of PA. The C-PPAC instrument is responsive to pharmacological and non-pharmacological interventions and to changes in clinically relevant variables. We compared the effect of PA behavioural modification interventions alongside pulmonary rehabilitation (PR) to PR alone on the C-PPAC scores in COPD patients with low baseline PA levels. METHODS: In this randomised controlled trial, 48 patients (means ± SD: FEV1: 50 ± 19%, baseline steps/day: 3450 ± 2342) were assigned 1:1 to receive PR alone, twice weekly for 8 weeks, or PA behavioural modification interventions (comprising motivational interviews, monitoring and feedback using a pedometer and goal setting) alongside PR (PR + PA). The C-PPAC instrument was used to assess PA experience, including a perspective of the amount and difficulty of PA. RESULTS: There were clinically important improvements in favour of the PR + PA interventions compared to PR alone in: 1) the C-PPAC total score (mean [95% CI] difference: 8 [4 to 12] points, p = 0.001), the difficulty (mean [95% CI] difference: 8 [3 to 13] points, p = 0.002) and the amount (mean [95% CI] difference 8 [3 to 16] points, p = 0.005) domains and 2) the CAT score (mean [95% CI] difference: -2.1 [-3.8 to -0.3] points, p = 0.025). CONCLUSION: PA behavioural modification interventions alongside PR improve the experiences of PA in patients with advanced COPD and low baseline PA levels. (NCT03749655).
Asunto(s)
Terapia Conductista/métodos , Conducta/fisiología , Ejercicio Físico/fisiología , Enfermedad Pulmonar Obstructiva Crónica/psicología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Anciano , Anciano de 80 o más Años , Tolerancia al Ejercicio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Cooperación del Paciente , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
In response to #COVID19, healthcare professionals should scale up virtual consultations for assessing core patient-reported outcomes and providing home-based rehabilitation programmes #COPD https://bit.ly/30gQEpG.
RESUMEN
Since the outbreak of COVID-19 in China in December 2019, a pandemic has rapidly developed on a scale that has overwhelmed health services in a number of countries. COVID-19 has the potential to lead to severe hypoxia; this is usually the cause of death if it occurs. In a substantial number of patients, adequate arterial oxygenation cannot be achieved with supplementary oxygen therapy alone. To date, there has been no clear guideline endorsement of ward-based non-invasive pressure support (NIPS) for severely hypoxic patients who are deemed unlikely to benefit from invasive ventilation. We established a ward-based NIPS service for COVID-19 PCR-positive patients, with severe hypoxia, and in whom escalation to critical care for invasive ventilation was not deemed appropriate. A retrospective analysis of survival in these patients was undertaken. Twenty-eight patients were included. Ward-based NIPS for severe hypoxia was associated with a 50% survival in this cohort. This compares favourably with Intensive Care National Audit and Research Centre survival data following invasive ventilation in a less frail, less comorbid and younger population. These results suggest that ward-based NIPS should be considered as a treatment option in an integrated escalation strategy in all units managing respiratory failure secondary to COVID-19.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Infecciones por Coronavirus , Fragilidad , Evaluación Geriátrica/métodos , Pandemias , Neumonía Viral , Unidades de Cuidados Respiratorios , Insuficiencia Respiratoria , Anciano de 80 o más Años , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Femenino , Fragilidad/diagnóstico , Fragilidad/fisiopatología , Fragilidad/terapia , Humanos , Pulmón/diagnóstico por imagen , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Oximetría/métodos , Oximetría/estadística & datos numéricos , Consumo de Oxígeno , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Unidades de Cuidados Respiratorios/métodos , Unidades de Cuidados Respiratorios/organización & administración , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , SARS-CoV-2 , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: COPD is a common progressive and debilitating medical condition. Mental health difficulties, such as anxiety and depression, have been reported in 25-50% of all patients with COPD. Interventions that reduce anxiety and depressive symptoms may affect COPD outcomes. Little data exists on the effect of managing these psychological difficulties in this group. METHOD: We studied the effects of a respiratory nurse-led cognitive behavioural therapy programme in 10 patients with COPD, assessing goal achievement, Hospital Anxiety and Depression Scale scores and medical admission rates. RESULTS: We used CBT in 10 patients with COPD across a range of severities. All 10 patients completed the CBT programme, with an average of four sessions (range 2-13). The mean score in the anxiety domain fell from 10.6 (range 6-15) before CBT to 3.8 after the intervention (range 1-7; p < 0.001). Similar improvements were seen in the depression domain, with a mean score before CBT of 10.9 (range 2-17), falling to a mean score after treatment of 5.2 (range 3-12; p < 0.001). A statistically significant reduction in the number of admissions was seen, with a mean of 1.1 admissions (total 11) before CBT to a mean of 0.2 admissions (total 2), p = 0.02. CONCLUSION: In this non-randomised study, a programme of individualised CBT in patients with COPD resulted in marked improvements in psychosocial impairment and a significant reduction in service use.
Asunto(s)
Terapia Cognitivo-Conductual , Enfermedad Pulmonar Obstructiva Crónica/terapia , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/psicología , Pruebas de Función RespiratoriaRESUMEN
Psychological ill health is very common in COPD; CBT may be a key step towards improving the care of COPD patients http://ow.ly/fb8j30onfPj.
RESUMEN
The APPLE COPD-ICON2 trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) without prior history of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the predefined cut-off of platelet inhibition measured using the Multiplate test in COPD patients. Eligible patients were randomised to aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only for 6â months. The primary outcome comprises inhibition (binary response) of arachidonic acid- (ASPI test, cut-off <40) and adenosine diphosphate- (ADP test, cut-off <46) induced platelet aggregation at 6â months. 543 patients were screened and 120 patients were recruited with mean age of 67.5â years; 47.5% patients were male. The per-protocol ASPI test response rate to aspirin was 68.3% (95% CI 52.3-80.9%). The per-protocol ADP test response rate to ticagrelaor was 68.8% (95% CI 50.4-82.6%). Platelet response to antiplatelet therapy with aspirin and ticagrelor was not observed in nearly one-third of COPD patients without prior history of cardiovascular disease. These findings support the high pro-thrombotic milieu and the need for further research to determine the effect of antiplatelet/antithrombotic therapy on cardiovascular morbidity and mortality in COPD patients.
RESUMEN
BACKGROUND: Despite widespread use of therapies such as inhaled corticosteroids (ICSs), people with chronic obstructive pulmonary disease (COPD) continue to suffer, have reduced life expectancy and utilise considerable NHS resources. Laboratory investigations have demonstrated that at low plasma concentrations (1-5 mg/l) theophylline markedly enhances the anti-inflammatory effects of corticosteroids in COPD. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of adding low-dose theophylline to a drug regimen containing ICSs in people with COPD at high risk of exacerbation. DESIGN: A multicentre, pragmatic, double-blind, randomised, placebo-controlled clinical trial. SETTING: The trial was conducted in 121 UK primary and secondary care sites. PARTICIPANTS: People with COPD [i.e. who have a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of < 0.7] currently on a drug regimen including ICSs with a history of two or more exacerbations treated with antibiotics and/or oral corticosteroids (OCSs) in the previous year. INTERVENTIONS: Participants were randomised (1 : 1) to receive either low-dose theophylline or placebo for 1 year. The dose of theophylline (200 mg once or twice a day) was determined by ideal body weight and smoking status. PRIMARY OUTCOME: The number of participant-reported exacerbations in the 1-year treatment period that were treated with antibiotics and/or OCSs. RESULTS: A total of 1578 people were randomised (60% from primary care): 791 to theophylline and 787 to placebo. There were 11 post-randomisation exclusions. Trial medication was prescribed to 1567 participants: 788 in the theophylline arm and 779 in the placebo arm. Participants in the trial arms were well balanced in terms of characteristics. The mean age was 68.4 [standard deviation (SD) 8.4] years, 54% were male, 32% smoked and mean FEV1 was 51.7% (SD 20.0%) predicted. Primary outcome data were available for 98% of participants: 772 in the theophylline arm and 764 in the placebo arm. There were 1489 person-years of follow-up data. The mean number of exacerbations was 2.24 (SD 1.99) for participants allocated to theophylline and 2.23 (SD 1.97) for participants allocated to placebo [adjusted incidence rate ratio (IRR) 0.99, 95% confidence interval (CI) 0.91 to 1.08]. Low-dose theophylline had no significant effects on lung function (i.e. FEV1), incidence of pneumonia, mortality, breathlessness or measures of quality of life or disease impact. Hospital admissions due to COPD exacerbation were less frequent with low-dose theophylline (adjusted IRR 0.72, 95% CI 0.55 to 0.94). However, 39 of the 51 excess hospital admissions in the placebo group were accounted for by 10 participants having three or more exacerbations. There were no differences in the reporting of theophylline side effects between the theophylline and placebo arms. LIMITATIONS: A higher than expected percentage of participants (26%) ceased trial medication; this was balanced between the theophylline and placebo arms and mitigated by over-recruitment (n = 154 additional participants were recruited) and the high rate of follow-up. The limitation of not using documented exacerbations is addressed by evidence that patient recall is highly reliable and the results of a small within-trial validation study. CONCLUSION: For people with COPD at high risk of exacerbation, the addition of low-dose oral theophylline to a drug regimen that includes ICSs confers no overall clinical or health economic benefit. This result was evident from the intention-to-treat and per-protocol analyses. FUTURE WORK: To promote consideration of the findings of this trial in national and international COPD guidelines. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 37. See the NIHR Journals Library website for further project information.
Chronic obstructive pulmonary disease (COPD) is a long-term lung disease that cannot be cured. The main symptom is shortness of breath on exertion. In the UK, about 1.2 million people have COPD. It is a major cause of death and costs the NHS > £1B a year. Sudden 'flare-ups' of symptoms often need emergency treatment, shorten life expectancy and reduce people's ability to get on with their lives. Theophylline is a drug that has been around for decades. In the past, it was used in high doses to treat COPD by opening up airways. However, its benefits were limited and it often caused unpleasant side effects. High-dose theophylline has been replaced by drugs administered by inhalers, such as inhaled corticosteroids (ICSs). Recent work in the laboratory and in animal models suggests that, at low dose, theophylline could make ICSs work better in COPD with none of the side effects of high-dose theophylline. The Theophylline With Inhaled CorticoSteroid (TWICS) trial tested whether or not adding low-dose theophylline reduces flare-ups in people with COPD taking ICSs. A total of 1578 people with COPD from 121 centres all over the UK took part. Participants were randomly divided into two groups: one group took low-dose theophylline and the other took dummy placebo pills. Participants were asked to attend visits at 6 and 12 months. A total of 791 participants were prescribed low-dose theophylline and 787 were prescribed dummy placebo pills. Although not everyone took the tablets for a whole year, it was possible to count the number of flare-ups in 98% of those taking part. In total, there were 3430 flare-ups. On average, the people taking low-dose theophylline had 2.24 flare-ups and the people taking placebo had 2.23 flare-ups. Overall, the trial showed that, for people with COPD, taking low-dose theophylline on top of steroid inhalers makes no real difference.
Asunto(s)
Corticoesteroides/administración & dosificación , Quimioterapia Combinada , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Teofilina/administración & dosificación , Administración por Inhalación , Anciano , Análisis Costo-Beneficio , Método Doble Ciego , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Evaluación de la Tecnología Biomédica , Reino UnidoRESUMEN
INTRODUCTION: The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. METHODS AND ANALYSIS: Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol-five dimensions-five levels of perceived problems (EQ5D-5L), St. George's COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. ETHICS AND DISSEMINATION: The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN43245574; Pre-results.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Grosor Intima-Media Carotídeo , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Prevención Primaria , Prueba de Estudio Conceptual , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Capacidad VitalRESUMEN
Anxiety is an important comorbidity in chronic obstructive pulmonary disease (COPD). We investigated if cognitive behavioural therapy (CBT), delivered by respiratory nurses, reduced symptoms of anxiety and was cost-effective. Patients with COPD and anxiety were randomised to CBT or self-help leaflets. Anxiety, depression and quality of life were measured at baseline, 3, 6 and 12â months. A cost-effectiveness analysis was conducted from a National Health Service hospital perspective and quality-adjusted life-years estimated using the EuroQol-5D questionnaire. In total, 279 patients were recruited. Group mean change from baseline to 3â months in the Hospital Anxiety and Depression Anxiety Subscale was 3.4 (95% CI 2.62-4.17, p<0.001) for the CBT group and 1.88 (95% CI 1.19-2.55, p<0.001) in the leaflet group. The CBT group was superior to leaflets at 3â months (mean difference in the Hospital Anxiety and Depression Anxiety Subscale was 1.52, 95% CI 0.49-2.54, p=0.003). Importantly, the CBT intervention was more cost-effective than leaflets at 12â months, significantly lowering hospital admissions and attendance at emergency departments. CBT delivered by respiratory nurses is a clinically and cost-effective treatment for anxiety in patients with COPD relative to self-help leaflets.
RESUMEN
Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD(20) methacholine (PD(20(M))), PD(15) hypertonic saline (PD(15(HS))) and their dose-response slopes (DRS(M) and DRS(HS)) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD(15(HS)) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3-123.5, p < 0.05), and time to BOS was significantly and negatively related to DRS(HS) (r = -0.5, p < 0.05) - that is, the greater the response, the shorter the time to BOS. Interestingly, DRS(HS) correlated positively with recipient:donor total lung capacity ratio (r = 0.5, p < 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development.
Asunto(s)
Hiperreactividad Bronquial/etiología , Bronquiolitis Obliterante/etiología , Trasplante de Pulmón/efectos adversos , Administración por Inhalación , Adulto , Anciano , Biopsia , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Broncoconstrictores/administración & dosificación , Broncoscopía , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Humanos , Masculino , Cloruro de Metacolina/administración & dosificación , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Solución Salina Hipertónica/administración & dosificación , Capacidad Pulmonar TotalRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014.