RESUMEN
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.
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Enfermedad Pulmonar Obstructiva Crónica , Comorbilidad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Fenotipo , Pronóstico , Suecia/epidemiologíaRESUMEN
INTRODUCTION: Since long-acting muscarinic antagonists (LAMA) are only indicated as add-on therapy in subjects with moderate-to-severe asthma, there are concerns whether LAMA monotherapy is associated with worse asthma control. AIM: To study the prevalence of LAMA monotherapy and its potential association with severe asthma exacerbations (SAE) in patients with asthma. METHODS: A cohort study (2007-2017) in the IPCI primary care database, in asthma patients aged 6-50, using LAMA during follow-up. Respiratory prescriptions were retrieved from the electronic medical records based on ATC code. Asthma treatment periods were created and categorized as LAMA mono, dual (LAMA + ICS), or triple therapy (LAMA + ICS + LABA). Relative rates (RR) of SAE, adjusting for patient characteristics, were estimated to compare treatments. RESULTS: From a total of 66,508 asthma patients, 1236 (1.9%) LAMA users were identified. Median age was 41 years, 65.9% were females. LAMA users were responsible for 3596 LAMA treatment periods of which 1390 (38.7%) were LAMA monotherapy, 553 (15.4%) dual therapy and 1653 (46.0%) triple therapy. The RR of SAE during LAMA monotherapy compared to dual therapy was 1.5 (95% CI 0.6-3.8). In patients alternating between mono and dual therapy (but never triple therapy), the RR for LAMA monotherapy increased to 5.7 (95% CI 1.4-23.6). CONCLUSIONS: This observational study shows that when LAMA is prescribed, it is often prescribed without concurrent ICS (LAMA monotherapy). LAMA monotherapy was associated with an increased risk of exacerbations when not used concurrently with ICS. This emphasizes the importance that LAMA should never be prescribed without concomitant ICS use in patients with asthma.
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Asma , Camélidos del Nuevo Mundo , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Corticoesteroides/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Adulto , Animales , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Antagonistas Muscarínicos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.
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Corticoesteroides/administración & dosificación , Asma/tratamiento farmacológico , Asma/epidemiología , Eosinofilia/epidemiología , Sistema de Registros , Índice de Severidad de la Enfermedad , Administración Oral , Corticoesteroides/efectos adversos , Adulto , Anciano , Asma/diagnóstico , Bélgica/epidemiología , Estudios Transversales , Esquema de Medicación , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM-induced respiratory responses. We describe the available literature on the topic including in vitro studies, findings in humans (ie observations in human cohorts, human controlled exposure and ex vivo studies) and in vivo animal studies. In brief, it has been shown that exposure to PM modulates the airway epithelium and promotes the production of several cytokines, including IL-1, IL-6, IL-8, IL-25, IL-33, TNF-α, TSLP and GM-CSF. Further, we propose that PM-induced type 2-promoting cytokines are important mediators in the acute and aggravating effects of PM on airway inflammation. Targeting these cytokines could therefore be a new approach in the treatment of asthma.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Alérgenos/inmunología , Hiperreactividad Bronquial/inmunología , Hipersensibilidad/inmunología , Material Particulado/efectos adversos , Animales , Asma/inmunología , Hiperreactividad Bronquial/genética , Hiperreactividad Bronquial/metabolismo , Hiperreactividad Bronquial/patología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Hipersensibilidad/genética , Hipersensibilidad/metabolismo , Hipersensibilidad/patología , Mediadores de Inflamación/metabolismo , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patologíaRESUMEN
BACKGROUND: Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure. METHODS: Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained from the identification analysis were used to perform a pathway analysis. RESULTS: Fourty Five SNP-by-ETS exposure interactions with p-values <10-4 were identified in the LifeLines study, two being replicated with nominally significant p-values (<0.05) in at least one of the replication cohorts. Three pathways were enriched in the pathway-level analysis performed in the identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways. CONCLUSION: This unique, first genome-wide gene-by-ETS interaction study on the level of FEV1 showed that pathways previously implicated in chronic obstructive pulmonary disease (COPD), a disease characterized by airflow obstruction, may also underlie susceptibility to impaired lung function in the context of ETS exposure.
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Sitios Genéticos , Enfermedades Pulmonares/genética , Pulmón/fisiopatología , Polimorfismo de Nucleótido Simple , Contaminación por Humo de Tabaco/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Femenino , Volumen Espiratorio Forzado , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Pulmón/metabolismo , Pulmón/patología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Fenotipo , Factores de Riesgo , Transducción de Señal/genética , Suiza/epidemiología , Factores de Tiempo , Factores de Necrosis Tumoral/metabolismo , Adulto Joven , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult-to-treat disease. OBJECTIVE: The goal of our study was to provide a detailed characterization of the frequent exacerbator phenotype and to identify risk factors associated with frequent and seasonal exacerbations. METHODS: Ninety-three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened and prospectively followed up for 1 year (NCT00555607). Medical history, baseline clinical data and biomarkers were used to assess risk factors for frequent exacerbations. RESULTS: During the study, 104 exacerbations were recorded in the SA group and 18 in the MA. Frequent exacerbators were characterized by use of higher doses of inhaled (1700 vs. 800 µg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%) and a more rapid decline in FEV1 /FVC ratio (-0.07 vs. -0.01 ΔFEV1 /FVC, frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively). CONCLUSION AND CLINICAL RELEVANCE: We were able to distinguish and characterize a subphenotype of asthma subjects--frequent exacerbators--who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require careful monitoring in clinical practice.
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Asma , Eosinófilos , Glucocorticoides/administración & dosificación , Índice de Severidad de la Enfermedad , Esputo/metabolismo , Administración por Inhalación , Administración Oral , Adolescente , Adulto , Anciano , Asma/tratamiento farmacológico , Asma/metabolismo , Asma/patología , Asma/fisiopatología , Eosinófilos/metabolismo , Eosinófilos/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Monitoreo FisiológicoRESUMEN
BACKGROUND: Although asthma is characterized by variable airways obstruction, most studies of asthma phenotypes are cross-sectional. The stability of phenotypes defined either by biomarkers or by physiological variables was assessed by repeated measures over 1 year in the Pan-European BIOAIR cohort of adult asthmatics. METHODS: A total of 169 patients, 93 with severe asthma (SA) and 76 with mild-to-moderate asthma (MA), were examined at six or more visits during 1 year. Asthma phenotype clusters were defined by physiological variables (lung function, reversibility and age of onset of the disease) or by biomarkers (eosinophils and neutrophils in induced sputum). RESULTS: After 1 year of follow-up, the allocation to clusters was changed in 23.6% of all asthma patients when defined by physiological phenotypes and, remarkably, in 42.3% of the patients when stratified according to sputum cellularity (P = 0.034). In the SA cohort, 30% and 48.6% of the patients changed allocation according to physiological and biomarker clustering, respectively. Variability of phenotypes was not influenced by change in oral or inhaled corticosteroid dose, nor by the number of exacerbations. Lower stability of single and repeated measure was found for all evaluated biomarkers (eosinophils, neutrophils and FeNO) in contrast to good stability of physiological variables (FEV1 ), quality of life and asthma control. CONCLUSION: Phenotypes determined by biomarkers are less stable than those defined by physiological variables, especially in severe asthmatics. The data also imply that definition of asthma phenotypes is improved by repeated measures to account for fluctuations in lung function, biomarkers and asthma control.
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Algoritmos , Asma/clasificación , Biomarcadores/análisis , Administración por Inhalación , Adolescente , Adulto , Anciano , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Estudios de Cohortes , Método Doble Ciego , Eosinófilos/inmunología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Fenotipo , Pruebas de Función Respiratoria , Esputo/inmunología , Adulto JovenRESUMEN
BACKGROUND AND AIM: Few well-designed randomized controlled trials (RCT) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease [COPD) have been conducted. We assessed the effectiveness of a pharmaceutical care program for patients with COPD. METHODS: The PHARMACOP-trial was a single-blind 3-month RCT, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged > or = 50 years, and with a smoking history > or = 10 pack-years. A computer-generated randomization sequence allocated patients to intervention (n = 371), receiving protocol-defined pharmacist care, or control group (n = 363), receiving usual pharmacist care 11:1 ratio, stratified by center). Interventions, focusing on inhalation technique and adherence to maintenance therapy, were carried out at start of the trial and at one month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnea, COPD specific and generic health status and smoking behavior. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. 42 patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score (Mean estimated difference [delta], 13.5%; 95% Confidence Interval [CI], 10.8-16.1; P < .0001] and medication adherence [(delta, 8.51%; 95% CI, 4.63-12.4; P < .0001) were significantly higher in the intervention group compared to the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs 35 hospitalizations; Rate Ratio, 0.28; 95% CI, 0.12-0.64; P = .003). No other significant between-group differences were observed. CONCLUSION: The PHARMACOP-trial demonstrates that pragmatic pharmacist care programs improve both inhalation technique and medication adherence in patients with COPD and could reduce hospitalization rates. The protocolled intervention used in this trial was specifically designed for and evaluated in (Belgian) community pharmacies. This may facilitate future implementation in the Belgian context.
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Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Anciano , Bélgica , Servicios Comunitarios de Farmacia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Farmacias , Farmacéuticos , Método Simple Ciego , Fumar/efectos adversosRESUMEN
Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.
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Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Esclerodermia Difusa , Esclerodermia Sistémica , Humanos , Enfermedades Raras/complicaciones , Enfermedades Raras/epidemiología , Enfermedades Raras/terapia , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/terapia , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Pulmonares Intersticiales/complicacionesRESUMEN
Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide and is expected to become the third leading cause of death in 2020. COPD is characterized by progressive airflow limitation, due to a combination of chronic inflammation and remodeling of the small airways (bronchiolitis) and loss of elastic recoil caused by destruction of the alveolar walls (emphysema). Lung cancer is the most important cause of cancer-related death in the world. (Cigarette) smoking is the principal culprit causing both COPD and lung cancer; in addition, exposure to environmental tobacco smoke, biomass fuel smoke, coal smoke and outdoor air pollution have also been associated with an increased incidence of both diseases. Importantly, smokers with COPD--defined as either not fully reversible airflow limitation or emphysema--have a two- to four-fold increased risk to develop lung cancer. In this review, we highlight several of the genetic, epigenetic and inflammatory mechanisms, which link COPD and carcinogenesis in the lungs. Elucidating the biological pathways and networks, which underlie the increased susceptibility of lung cancer in patients with COPD, has important implications for screening, prevention, diagnosis and treatment of these two devastating pulmonary diseases.
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Neoplasias Pulmonares/etiología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Fumar/efectos adversos , Animales , Exposición a Riesgos Ambientales/efectos adversos , Epigénesis Genética , Humanos , Inflamación/epidemiología , Inflamación/etiología , Inflamación/terapia , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Tamizaje Masivo/métodos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Fumar/epidemiologíaRESUMEN
OBJECTIVE: Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 µg), formoterol fumarate (FF, 5 µg) and glycopyrronium (G, 9 µg)) in combination with inhalation technique training. METHODS: A total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up. RESULTS: Before switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased. CONCLUSIONS: This observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Administración por Inhalación , Resultado del Tratamiento , Fumarato de Formoterol , Beclometasona , Nebulizadores y Vaporizadores , Atención al Paciente , Combinación de MedicamentosRESUMEN
BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.
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Asma , Aplicaciones Móviles , Rinitis Alérgica , Humanos , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/epidemiología , Asma/diagnóstico , Asma/epidemiología , Proyectos de InvestigaciónRESUMEN
INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.
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Spirometry is used worldwide to diagnose respiratory disease, and it is a validated measure to assess airway obstruction. Irreversible airway obstruction is the defining feature of chronic obstructive pulmonary disease (COPD). Thus, an FEV(1)/FVC ratio <70% is used to diagnose COPD, and the severity is thereafter based on the level of FEV(1). This definition is widely used in clinical practice and research, yet may lead to confusion with respect to the diagnosis associated with the presence of airway obstruction. The three main reasons are the following: (1) fixed airflow obstruction may be the result of specific diagnoses such as cystic fibrosis; (2) FEV(1)/FVC ratio changes with ageing, and it is therefore inappropriate to use the same ratio at 40 and 90 years, leaving aside gender differences; (3) even when specific diagnoses are excluded, fixed airflow obstruction may be the end-stage of many different underlying processes. The authors believe that they have strong arguments that a COPD diagnosis based solely on spirometric values is nonsense. More sophisticated lung function tests, such as plethysmography, forced oscillation and lung clearance index, may help further to delineate the characteristics of low lung function. However, these are not feasible in most clinical contexts and in epidemiologic studies. Therefore, the authors throw down the gauntlet: spirometry is an essential tool in patient evaluation but dangerous for disease diagnosis, and the term COPD should only be used in the appropriate clinical (diagnostic) context.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Espirometría/métodos , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Sensibilidad y EspecificidadRESUMEN
Pentraxin (PTX)3 is involved in antimicrobial defence, apoptotic cell clearance and extracellular matrix stability. As these processes are altered in chronic obstructive pulmonary disease (COPD), we aimed to investigate PTX3 expression in patients with this disease. PTX3 expression was quantified by immunohistochemical staining of lung tissue from never-smokers, smokers without COPD, and in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II and III-IV. mRNA expression was examined in total lung tissue by quantitative RT-PCR. PTX3 concentration was measured in induced sputum and plasma by ELISA. PTX3 is mainly localised in the interstitium of the small airways and alveolar walls. There were no significant differences in pulmonary, sputum and plasma PTX3 expression between study groups. However, PTX3 expression in small airways correlated significantly with forced expiratory volume in 1 s (r = 0.35, p = 0.004). In the alveolar walls, PTX3 expression correlated significantly with carbon monoxide transfer coefficient (r = 0.28, p = 0.04). In sputum, PTX3 levels were highly correlated with the number of neutrophils. Finally, systemic levels of PTX3 tended to be lower in severe COPD compared with mild COPD. In COPD, airflow limitation and reduced transfer coefficient for carbon monoxide are associated with lower pulmonary interstitial expression of PTX3.
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Proteína C-Reactiva/genética , Pulmón/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Componente Amiloide P Sérico/genética , Adulto , Anciano , Bronquiolos/fisiología , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Alveolos Pulmonares/fisiología , Arteria Pulmonar/fisiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , ARN Mensajero/metabolismo , Mucosa Respiratoria/fisiología , Componente Amiloide P Sérico/metabolismo , Fumar/metabolismo , Fumar/fisiopatología , Esputo/metabolismoRESUMEN
BACKGROUND: Tiotropium has been associated with an increased risk of mortality and/or cardiovascular events. Recent data from RCTs suggests tiotropium Handihaler to be safe, but its safety has not yet been fully investigated under real-life circumstances. METHODS: We conducted 2 nested case-control studies in a COPD cohort from the Dutch IPCI database. In the first case-control study, cases had a cardiovascular or cerebrovascular endpoint (CCVE): stroke and transient ischemic attack (TIA), myocardial infarction, heart failure and/or ventricular arrhythmia. In the second, cases were all patients who died. Cases were matched to controls on age, sex and index date. Conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (CI) for tiotropium vs. long-acting beta-agonists (LABA). RESULTS: Within a cohort of 6788 COPD patients, 784 CCVE's and 1032 deaths were reported. Compared to current LABA use, use of tiotropium Handihaler was neither associated with an increased risk of a CCVE (OR(adj) 0.89, 95% 0.55-1.44) nor with an increased risk of death (OR(adj) 0.79, 95% CI 0.49-1.28). CONCLUSIONS: In real life, use of tiotropium Handihaler in COPD patients is not associated with an increased risk of a CCVE or mortality compared to LABA.
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Broncodilatadores/efectos adversos , Broncodilatadores/uso terapéutico , Enfermedades Cardiovasculares/inducido químicamente , Trastornos Cerebrovasculares/inducido químicamente , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/efectos adversos , Derivados de Escopolamina/uso terapéutico , Agonistas Adrenérgicos beta/efectos adversos , Adulto , Factores de Edad , Anciano , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/mortalidad , Broncodilatadores/administración & dosificación , Enfermedades Cardiovasculares/mortalidad , Estudios de Casos y Controles , Trastornos Cerebrovasculares/mortalidad , Estudios de Cohortes , Intervalos de Confianza , Bases de Datos Factuales , Determinación de Punto Final , Femenino , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/mortalidad , Humanos , Ataque Isquémico Transitorio/inducido químicamente , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Derivados de Escopolamina/administración & dosificación , Factores Sexuales , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Bromuro de TiotropioRESUMEN
Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1ß, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses. We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1ß antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1ß mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD. In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1ß. Interestingly, CS-induced inflammation occurred independently of IL-1ß activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1ß were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers. These results suggest that not only IL-1ß but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 1/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Fumar/efectos adversos , Animales , Anticuerpos Neutralizantes/farmacología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Humanos , Inflamación , Interleucina-1alfa/antagonistas & inhibidores , Interleucina-1beta/antagonistas & inhibidores , Pulmón/patología , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Receptores de Interleucina-1/metabolismo , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Adulto , Estudios Transversales , Europa (Continente) , Volumen Espiratorio Forzado , Estado de Salud , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Atención Primaria de Salud/métodos , Neumología/métodos , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting ß(2)-agonists (LABA), and with as-needed short-acting ß(2)-agonists (SABA) or LABA. Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6-12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model. The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36% versus pooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52% versus the same maintenance dose of ICS/LABA (RR 0.48; p<0.001); there were nonsignificant reductions versus higher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbations versus as-needed SABA (RR 0.96). Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.
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Asma/complicaciones , Asma/terapia , Resfriado Común/complicaciones , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Budesonida/administración & dosificación , Niño , Preescolar , Método Doble Ciego , Etanolaminas/administración & dosificación , Femenino , Fumarato de Formoterol , Humanos , Masculino , Persona de Mediana Edad , Distribución de Poisson , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estudios Retrospectivos , Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by biased Th2 inflammation and CRS without nasal polyps (CRSsNP) by a Th1 immune response. Colonization by Staphylococcus aureus is increased in CRSwNP. We aimed to determine macrophage phenotypes in nasal mucosa of CRSwNP and CRSsNP and to examine phagocytosis of S. aureus in these pathologies. METHODS: Macrophage phenotyping was performed by immunohistochemical staining on nasal mucosa sections from 28 patients; in addition flow cytometry analysis was performed. Tissue homogenate protein levels of IFN-γ, IL-5, IL-6, IL-1ß, TGF-ß, eosinophil cationic protein (ECP) and total IgE were analyzed and correlated with macrophage subtypes. Phagocytosis of S. aureus was analyzed by flow cytometry. Survival of S. aureus in Thp1 cells in the presence of polarizing cytokines was studied in vitro. RESULTS: By immunohistochemical analysis more M2 macrophages were present in CRSwNP than in CRSsNP. This also was positively correlated with increased levels of IL-5, ECP and locally produced IgE and decreased levels of IL-6, IL-1ß and IFN-γ. FACS analysis of dissociated nasal tissue confirmed the presence of increased numbers of M2 macrophages (CD206(+) HLADR(+) CD14(+) CD11c(+) CD20(-) ) in CRSwNP as compared to controls, while the number of M1 macrophages (CD206(-) HLADR(+) CD14(+) CD11c(int) CD16(-) CD20(-) ) was not different. Phagocytosis of S. aureus by human tissue derived macrophages was reduced in CRSwNP as compared to macrophages from the control inferior turbinates. CONCLUSIONS: Decreased phagocytosis of S. aureus and an M2 activation phenotype in CRSwNP could potentially contribute to persistence of chronic inflammation in CRSwNP.