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1.
Eur Respir J ; 59(1)2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34172466

RESUMEN

BACKGROUND: The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations. METHODS: We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants. RESULTS: Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL-1 (asthma, 22 studies); 200-400 cells·µL-1 (severe asthma, eight studies); 150-183 cells·µL-1 (COPD, six studies); and 100-160 cells·µL-1 (controls, three studies); and 100-200 cells·µL-1 (general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity. CONCLUSION: EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.


Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Adolescente , Asma/diagnóstico , Niño , Eosinófilos , Humanos , Recuento de Leucocitos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico
2.
Eur Respir J ; 57(5)2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33303555

RESUMEN

INTRODUCTION: The aim of this study was to examine the association between blood eosinophil levels and the decline in lung function in individuals aged >40 years from the general population. METHODS: The study evaluated the eosinophil counts from thawed blood in 1120 participants (mean age 65 years) from the prospective population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. Participants answered interviewer-administered respiratory questionnaires and performed pre-/post-bronchodilator spirometric tests at 18-month intervals; computed tomography (CT) imaging was performed at baseline. Statistical analyses to describe the relationship between eosinophil levels and decline in forced expiratory volume in 1 s (FEV1) were performed using random mixed-effects regression models with adjustments for demographics, smoking, baseline FEV1, ever-asthma and history of exacerbations in the previous 12 months. CT measurements were compared between eosinophil subgroups using ANOVA. RESULTS: Participants who had a peripheral eosinophil count of ≥300 cells·µL-1 (n=273) had a greater decline in FEV1 compared with those with eosinophil counts of <150 cells·µL-1 (n=430; p=0.003) (reference group) and 150-<300 cells·µL-1 (n=417; p=0.003). The absolute change in FEV1 was -32.99 mL·year-1 for participants with eosinophil counts <150 cells·µL-1; -38.78 mL·year-1 for those with 150-<300 cells·µL-1 and -67.30 mL·year-1 for participants with ≥300 cells·µL-1. In COPD, higher eosinophil count was associated with quantitative CT measurements reflecting both small and large airway abnormalities. CONCLUSION: A blood eosinophil count of ≥300 cells·µL-1 is an independent risk factor for accelerated lung function decline in older adults and is related to undetected structural airway abnormalities.


Asunto(s)
Eosinófilos , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Canadá , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Estudios Prospectivos
3.
Eur Respir J ; 57(6)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33334936

RESUMEN

Suboptimal adherence to maintenance therapy contributes to poor asthma control and exacerbations. This study evaluated the effect of different elements of a connected inhaler system (CIS), comprising clip-on inhaler sensors, a patient-facing app and a healthcare professional (HCP) dashboard, on adherence to asthma maintenance therapy.This was an open-label, parallel-group, 6-month, randomised controlled trial in adults with uncontrolled asthma (asthma control test (ACT) score less than 20) on fixed-dose inhaled corticosteroids/long-acting ß-agonist maintenance therapy (n=437). All subjects received fluticasone furoate/vilanterol ELLIPTA dry-powder inhalers for maintenance and salbutamol/albuterol metered-dose inhalers for rescue, with a sensor attached to each inhaler. Participants were randomised to one of five CIS study arms (allocation ratio 1:1:1:1:1) reflecting the recipient of the data feedback from the sensors, as follows: 1) maintenance use to participants and HCPs (n=87); 2) maintenance use to participants (n=88); 3) maintenance and rescue use to participants and HCPs (n=88); 4) maintenance and rescue use to participants (n=88); and 5) no feedback (control) (n=86).For the primary endpoint, observed mean±sd adherence to maintenance therapy over months 4-6 was 82.2±16.58% (n=83) in the "maintenance to participants and HCPs" arm and 70.8±27.30% (n=85) in the control arm. The adjusted least squares mean±se was 80.9±3.19% and 69.0±3.19%, respectively (study arm difference: 12.0%, 95% CI 5.2-18.8%; p<0.001). Adherence was also significantly greater in the other CIS arms versus the control arm. The mean percentage of rescue medication free days (months 4-6) was significantly greater in participants receiving data on their rescue use compared with controls. ACT scores improved in all study arms with no significant differences between groups.A CIS can improve adherence to maintenance medication and reduce rescue medication use in patients with uncontrolled asthma.


Asunto(s)
Antiasmáticos , Asma , Administración por Inhalación , Adulto , Albuterol/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Combinación de Medicamentos , Humanos , Cumplimiento de la Medicación , Nebulizadores y Vaporizadores
4.
Br J Clin Pharmacol ; 87(2): 483-493, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32484940

RESUMEN

AIMS: To compare the airway potency, systemic activity and therapeutic index of three inhaled corticosteroids that differ in glucocorticoid receptor binding affinity, physicochemical and pharmacokinetic properties. METHODS: This escalating-dose, placebo-controlled, cross-over study randomised adults with asthma to 1 or 2 treatment periods with ≥25 days washout in-between. Each treatment period comprised five 7-day dose escalations (µg/d): fluticasone furoate (FF; 25 → 100 → 200 → 400 → 800), fluticasone propionate (FP; 50 → 200 → 500 → 1000 → 2000), budesonide (BUD; 100 → 400 → 800 → 1600 → 3200) or placebo. Airway hyperresponsiveness to adenosine-5'-monophosphate (AMP PC20 ) was assessed on day 8. Plasma cortisol was assessed on day 1 (predose baseline) and from pre-PM dose on day 6 to pre-PM dose day 7 (24-h weighted mean). RESULTS: Fifty-four subjects were randomised. FF showed greater airway potency than FP and BUD (AMP PC20 dose at which 50% of the maximum effect is achieved [ED50 ] values: 48.52, 1081.27 and 1467.36 µg/d, respectively). Systemic activity (cortisol suppression) ED50 values were 899.99, 1986.05 and 1927.42 µg/d, respectively. The therapeutic index (ED50 cortisol suppression/ED50 AMP PC20 ) was wider for FF (18.55) than FP (1.84) and BUD (1.31). FF 100 µg/d and 200 µg/d were both comparable in terms of airway potency with high doses of FP (≥1000 µg twice daily [BID]) and BUD (≥1500 µg/BID). The systemic activity of FF 100 µg/d and 200 µg/d (cortisol suppression: 7.41% and 14.28%, respectively) was comparable with low doses of FP (100 µg/BID and 250 µg/BID) and BUD (100 µg/BID and 200 µg/BID). CONCLUSION: This study provides evidence that FF can provide more protection against airway hyperresponsiveness, with less systemic activity, than FP or BUD. This suggests that all inhaled corticosteroids are not therapeutically similar and may differ in their therapeutic index. (203162; NCT02991859).


Asunto(s)
Antiasmáticos , Asma , Administración por Inhalación , Corticoesteroides/uso terapéutico , Adulto , Androstadienos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Estudios Cruzados , Método Doble Ciego , Fluticasona , Humanos , Hidrocortisona/uso terapéutico , Índice Terapéutico
5.
Respir Res ; 21(1): 5, 2020 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-31907054

RESUMEN

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Glucocorticoides/administración & dosificación , Neumonía/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Administración por Inhalación , Anciano , Quimioterapia Combinada , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Factores de Riesgo , Reino Unido/epidemiología
6.
COPD ; 17(1): 81-89, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31833441

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a complex multi-morbid disorder with significant cardiac mortality. Current cardiovascular risk prediction models do not include COPD. We investigated whether COPD modifies future cardiovascular risk to determine if it should be considered in risk prediction models.Case-control study using baseline data from two randomized controlled trials performed between 2012 and 2015. Of the 90 eligible subjects, 26 COPD patients with lung hyperinflation were propensity matched for 10-year global cardiovascular risk score (QRISK2) with 26 controls having normal lung function. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. Differences in pulse wave velocity (PWV), total arterial compliance (TAC) and aortic distensibility were main outcome measures.PWV (mean difference 1.0 m/s, 95% CI 0.02-1.92; p = 0.033) and TAC (mean difference -0.27 mL/m2/mmHg, 95% CI 0.39-0.15; p < 0.001) were adversely affected in COPD compared to the control group. The PWV difference equates to an age, sex and risk-factor adjusted increase in relative risk of cardiovascular events and mortality of 14% and 15%, respectively.There were no differences in aortic distensibility. In the whole cohort (n = 90) QRISK2 (ß = 0.045, p = 0.005) was associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV were modified by COPD, where the interaction term reached significance (p = 0.014). FEV1 (ß = 0.055 (0.027), p = 0.041) and pulse (B = -0.006 (0.002), p = 0.003) were associated with TAC in multivariate analysis.Markers of cardiovascular outcomes are adversely affected in COPD patients with lung hyperinflation compared to controls matched for global cardiovascular risk. Cardiovascular risk algorithms may benefit from the addition of a COPD variable to improve risk prediction and guide management.HAPPY London ClinicalTrials.gov: NCT01911910 and HZC116601; ClinicalTrials.gov: NCT01691885.


Asunto(s)
Enfermedades Cardiovasculares/diagnóstico por imagen , Factores de Riesgo de Enfermedad Cardiaca , Ventrículos Cardíacos/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Análisis de la Onda del Pulso , Rigidez Vascular , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Ventrículos Cardíacos/patología , Humanos , Hipertensión/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Volumen Residual , Capacidad Pulmonar Total , Capacidad Vital
7.
Respir Res ; 20(1): 195, 2019 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-31443653

RESUMEN

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; however, no definitive biomarkers of risk have been established. We hypothesized that blood neutrophils would help predict pneumonia risk in COPD. METHODS: A meta-analysis of randomized, double-blind clinical trials of COPD patients meeting the following criteria were selected from the GlaxoSmithKline trial registry: ≥1 inhaled corticosteroid-containing (ICS) arm (fluticasone propionate/salmeterol or fluticasone furoate/vilanterol), a control arm (non-ICS), pre-randomization blood neutrophil counts, ≥24-week duration. The number of patients with pneumonia events and time to first event (Kaplan-Meier analysis) were evaluated (post-hoc), stratified by baseline blood neutrophil count and ICS use. A Cox proportional hazards model was used to calculate hazard ratios (HR), split by median baseline blood neutrophils. RESULTS: Ten studies (1998 to 2011) with 11,131 patients were identified. The ICS (n = 6735) and non-ICS (n = 4396) cohorts were well matched in neutrophil distributions and demographics. Increasing neutrophil count was associated with an increased proportion of patients with pneumonia events; patients below the median neutrophil count were at less risk of a pneumonia event (HR, 0.75 [95% confidence interval 0.61-0.92]), and had longer time to a first event, compared with those at/above the median. The increase in pneumonia risk by neutrophil count was similar between the two cohorts. CONCLUSIONS: Increased blood neutrophils in COPD were associated with increased pneumonia risk, independent of ICS use. These data suggest blood neutrophils may be a useful marker in defining treatment pathways in COPD.


Asunto(s)
Recuento de Leucocitos , Neutrófilos , Neumonía/diagnóstico , Neumonía/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neumonía/epidemiología , Valor Predictivo de las Pruebas , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo
8.
Eur Respir J ; 51(6)2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29773688

RESUMEN

Asthma control is suboptimal for many sufferers despite the existence of effective treatments. Patients' self-management is influenced by their perceptions of asthma and its treatment. This study explored sufferers' perceptions of asthma control and their influence on self-management behaviours.Participants (n=42) recruited from primary and secondary care asthma clinics in London in the UK each underwent a qualitative interview exploring perceptions and experiences of asthma control. Purposive sampling ensured variation in disease severity, degree of asthma control, age and socioeconomic status. Grounded theory was employed in thematic analysis of transcribed interviews.Five themes relating to perceptions of asthma control and self-management were identified: personal meaning of control, intermittent prevention, compromising control to avoid medication, pharmacological agents overemphasised in control and the role of asthma review in control. Within the first theme, some participants had an internal barometer of the level of symptoms that indicated their asthma was getting "out of control" that was set much higher than Asthma Control Test criteria.The findings provide new insights into patients' perceptions of asthma control. Symptoms indicative of poor control were often tolerated as part of living with asthma. Identification of barriers and drivers to self-management highlight potential targets for strategies aimed at optimising asthma management.


Asunto(s)
Antiasmáticos/uso terapéutico , Asma/terapia , Conocimientos, Actitudes y Práctica en Salud , Automanejo/métodos , Adolescente , Adulto , Femenino , Teoría Fundamentada , Humanos , Entrevistas como Asunto , Londres , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Adulto Joven
9.
Br J Nutr ; 120(8): 891-900, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30132432

RESUMEN

SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, P for trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (P for trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.


Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Infecciones del Sistema Respiratorio/genética , Virosis/genética , Adulto , Anciano , Citocinas/genética , Citocinas/metabolismo , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad
10.
J Asthma ; 55(8): 890-897, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-28783413

RESUMEN

OBJECTIVE: Symptoms, including night-time awakenings, affect the quality of life of people with asthma. Fluticasone furoate/vilanterol (FF/VI) reduces exacerbations, improves lung function, and rescue-free and symptom-free 24-hour periods in patients with asthma. These post hoc analyses compared daytime and night-time symptoms in patients with asthma who received FF/VI, versus FF, fluticasone propionate (FP) or placebo. METHODS: Daytime and night-time symptoms were collected via electronic daily diary cards in three Phase III randomized studies of once-daily FF/VI in patients with uncontrolled asthma on inhaled corticosteroids (ICSs) ± long-acting beta2 agonists (n = 609/1039/586). Endpoints included change from baseline in symptom-free days and nights (analyzed by Analysis of Covariance, covariates: baseline, region, sex, age, and treatment), time for patients to achieve seven consecutive symptom-free nights (analyzed by Cox proportional hazards' model, covariates as above), and proportion of patients experiencing 100% symptom-free nights per week (analyzed by logistic regression, covariates: percentage of symptom-free nights, sex, age, and treatment). RESULTS: Improvements in symptom-free days and nights were generally observed for all treatments. More patients who received FF/VI experienced 100% symptom-free nights in the last week of the treatment period than patients who received ICS alone or placebo. FF/VI also reduced time to achieve seven consecutive symptom-free nights. Patients with at least one night of symptoms at baseline experienced an additional 2.7 and 2.0 symptom-free nights per week with FF/VI 100/25 µg, versus 1.9 and 1.7 with FF alone; similar findings were seen with FF/VI 200/25 µg. CONCLUSIONS: Benefits in terms of symptom-free days and nights were observed for patients receiving FF/VI versus comparators in these post hoc analyses.


Asunto(s)
Androstadienos/administración & dosificación , Asma/tratamiento farmacológico , Alcoholes Bencílicos/administración & dosificación , Clorobencenos/administración & dosificación , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Adulto , Asma/complicaciones , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Sueño-Vigilia/etiología , Resultado del Tratamiento , Adulto Joven
11.
Eur Respir J ; 50(4)2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28982774

RESUMEN

Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 µg plus fluticasone propionate 500 µg or salmeterol 50 µg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.


Asunto(s)
Carga Bacteriana , Glucocorticoides , Efectos Adversos a Largo Plazo , Enfermedad Pulmonar Obstructiva Crónica , Infecciones del Sistema Respiratorio , Esputo/microbiología , Carga Viral , Administración por Inhalación , Carga Bacteriana/efectos de los fármacos , Carga Bacteriana/métodos , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Monitoreo de Drogas/métodos , Eosinófilos/patología , Femenino , Fluticasona/administración & dosificación , Fluticasona/efectos adversos , Volumen Espiratorio Forzado , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/microbiología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Pruebas de Función Respiratoria , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Xinafoato de Salmeterol/administración & dosificación , Xinafoato de Salmeterol/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Carga Viral/métodos
12.
Am J Respir Crit Care Med ; 193(7): 717-26, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26550687

RESUMEN

RATIONALE: Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. OBJECTIVES: To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. METHODS: Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting ß2-agonist fluticasone furoate/vilanterol 100/25 µg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. MEASUREMENTS AND MAIN RESULTS: There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. CONCLUSIONS: Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Androstadienos/administración & dosificación , Alcoholes Bencílicos/administración & dosificación , Clorobencenos/administración & dosificación , Corazón/efectos de los fármacos , Pulmón/fisiopatología , Miocardio/patología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Anciano , Broncodilatadores/administración & dosificación , Estudios Cruzados , Combinación de Medicamentos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Corazón/fisiopatología , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología
13.
BMC Pulm Med ; 17(1): 172, 2017 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-29207997

RESUMEN

CORRECTION: After publication of this work [1] it was noticed that the author name Rachael L. DiSantostefano was not spelt correctly as there was a space in her surname between 'Di' and 'Santostefano'. The publisher apologises for this error.

14.
BMC Pulm Med ; 17(1): 31, 2017 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-28173781

RESUMEN

BACKGROUND: Inhaled corticosteroids (ICS) are the primary treatment for persistent asthma. Currently available ICS have differing particle size due to both formulation and propellant, and it has been postulated that this may impact patient outcomes. This structured literature review and meta-analysis compared the effect of small and standard particle size ICS on lung function, symptoms, rescue use (when available) and safety in patients with asthma as assessed in head-to-head randomized controlled trials (RCTs). METHODS: A systematic literature search of MEDLINE was performed to identify RCTs (1998-2014) evaluating standard size (fluticasone propionate-containing medications) versus small particle size ICS medication in adults and children with asthma. Efficacy outcomes included forced expiratory volume in 1 s (FEV1), morning peak expiratory flow (PEF), symptom scores, % predicted forced expiratory flow between 25 and 75% of forced vital capacity (FEF25-75%), and rescue medication use. Safety outcomes were also evaluated when available. RESULTS: Twenty-three independent trials that met the eligibility criteria were identified. Benefit-risk plots did not demonstrate any clinically meaningful differences across the five efficacy endpoints considered and no appreciable differences were noted for most safety endpoints. Meta-analysis results, using a random-effects model, demonstrated no significant difference between standard and small size particle ICS medications in terms of effects on mean change from baseline FEV1 (L) (-0.011, 95% confidence interval [CI]: -0.037, 0.014 [N = 3524]), morning PEF (L/min) (medium/low doses: -3.874, 95% CI: -10.915, 3.166 [N = 1911]; high/high-medium doses: 5.551, 95% CI: -1.948, 13.049 [N = 749]) and FEF25-75% predicted (-2.418, 95% CI: -6.400; 1.564 [N = 115]). CONCLUSIONS: Based on the available literature, no clinically significant differences in efficacy or safety were observed comparing small and standard particle size ICS medications for the treatment of asthma. TRIAL REGISTRATION: GSK Clinical Study Register No: 202012 .


Asunto(s)
Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Tamaño de la Partícula , Administración por Inhalación , Volumen Espiratorio Forzado , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
BMC Pulm Med ; 17(1): 75, 2017 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-28454528

RESUMEN

BACKGROUND: To analyse the efficacy of fluticasone propionate (FP) alone and combined with salmeterol (SAL) in achieving guideline-defined asthma control in Asian patients. METHODS: A post hoc analysis of the GOAL study in which patients were stratified by prior-medication use into inhaled corticosteroid (ICS)-naïve (Stratum [S] 1), low-dose ICS (S2), and medium-dose ICS (S3), and randomised to receive FP/SAL or FP. Doses were stepped-up every 12 weeks until Totally Controlled asthma or maximum dose was reached (PhI) and then maintained until study end (PhII). The primary endpoint was the proportion of patients achieving Well-Controlled asthma during PhI. Additional endpoints included Total Control and adverse events. Asian and non-Asian patients were analysed separately. RESULTS: In Asian patients in PhI, 74% (n = 87/118) in S1 achieved Well-Controlled asthma with FP/SAL versus 74% (n = 89/121) with FP alone (p = 0.839); corresponding values were 76% (n = 81/107) versus 60% (n = 62/104; p = 0.005) in S2, and 58% (n = 59/102) versus 43% (n = 41/95; p = 0.015) in S3. More patients in all three strata achieved Totally Controlled asthma with FP/SAL versus FP alone. Control was achieved more rapidly and with lower ICS doses with FP/SAL versus FP. A high proportion of patients who achieved control during PhI maintained control during PhII. Similar trends were found in non-Asian patients. No new safety concerns were identified. CONCLUSIONS: A greater proportion of Asian patients (S2 and S3, for Well-Controlled; all strata, for Totally Controlled) achieved guideline-defined asthma control with FP/SAL versus FP alone. High proportions of Asian patients in S1 achieved Well-Controlled asthma in both treatment groups.


Asunto(s)
Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Fluticasona/administración & dosificación , Xinafoato de Salmeterol/administración & dosificación , Corticoesteroides/administración & dosificación , Adulto , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Internacionalidad , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Calidad de Vida , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
16.
Thorax ; 71(2): 118-25, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26585525

RESUMEN

OBJECTIVE: We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. METHODS: Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57-75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. RESULTS: For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. DISCUSSION: Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Eosinófilos/citología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Combinación Fluticasona-Salmeterol/administración & dosificación , Volumen Espiratorio Forzado/fisiología , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del Tratamiento
17.
Eur Respir J ; 47(5): 1374-82, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26917606

RESUMEN

Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 µg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted.


Asunto(s)
Corticoesteroides/uso terapéutico , Eosinófilos/citología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Adulto , Anciano , Broncodilatadores/administración & dosificación , Femenino , Fluticasona/administración & dosificación , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función Respiratoria , Estudios Retrospectivos , Fumar
18.
Eur Respir J ; 48(2): 320-30, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27418551

RESUMEN

Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting ß2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017.


Asunto(s)
Corticoesteroides/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Androstadienos/administración & dosificación , Alcoholes Bencílicos/administración & dosificación , Clorobencenos/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Quinuclidinas/administración & dosificación , Adulto , Anciano , Broncodilatadores/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Guías de Práctica Clínica como Asunto , Estudios Prospectivos
20.
Thorax ; 70(10): 953-60, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26063508

RESUMEN

RATIONALE: Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against acute respiratory infection (ARI) are lacking. OBJECTIVE: To conduct a clinical trial of high-dose versus low-dose vitamin D3 supplementation for ARI prevention in residents of sheltered-accommodation housing blocks ('schemes') and their carers in London, UK. MEASUREMENTS AND METHODS: Fifty-four schemes (137 individual participants) were allocated to the active intervention (vitamin D3 2.4 mg once every 2 months +10 µg daily for residents, 3 mg once every 2 months for carers), and 54 schemes with 103 participants were allocated to control (placebo once every 2 months +vitamin D3 10 µg daily for residents, placebo once every 2 months for carers) for 1 year. Primary outcome was time to first ARI; secondary outcomes included time to first upper/lower respiratory infection (URI/LRI, analysed separately), and symptom duration. MAIN RESULTS: Inadequate vitamin D status was common at baseline: 220/240 (92%) participants had serum 25(OH)D concentration <75 nmol/L. The active intervention did not influence time to first ARI (adjusted HR (aHR) 1.18, 95% CI 0.80 to 1.74, p=0.42). When URI and LRI were analysed separately, allocation to the active intervention was associated with increased risk of URI (aHR 1.48, 95% CI 1.02 to 2.16, p=0.039) and increased duration of URI symptoms (median 7.0 vs 5.0 days for active vs control, adjusted ratio of geometric means 1.34, 95% CI 1.09 to 1.65, p=0.005), but not with altered risk or duration of LRI. CONCLUSIONS: Addition of intermittent bolus-dose vitamin D3 supplementation to a daily low-dose regimen did not influence risk of ARI in older adults and their carers, but was associated with increased risk and duration of URI. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT01069874.


Asunto(s)
Colecalciferol/uso terapéutico , Suplementos Dietéticos , Infecciones del Sistema Respiratorio/prevención & control , Vitaminas/uso terapéutico , Enfermedad Aguda , Anciano , Cuidadores , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Casas de Salud
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