Eduard Monsó

Guía clínica para el diagnóstico y el tratamiento de la enfermedad pulmonar obstructiva crónica

La enfermedad pulmonar obstructiva crónica (EPOC) es la de mayor prevalencia e impacto socioeconómico de todas las enfermedades respiratorias. Consciente de esta importancia, la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) ha elaborado recomendaciones específicas para su diagnóstico y tratamiento, la primera de ellas en 19921 y la segunda en 19962. Desde la publicación de esta última normativa ha habido un renovado interés en el estudio de la EPOC y se han producido novedades importantes en su tratamiento. Asimismo, en estos últimos años se han publicado guías clínicas por parte de sociedades científicas internacionales (European Respiratory Society, American Thoracic Society3,4) y se ha puesto en marcha la Global Obstructive Lung Disease Initiative, auspiciada por la Organización Mundial de la Salud y los Institutos Nacionales de Salud de Estados Unidos, cuyo objetivo es armonizar la atención clínica de estos pacientes en los distintos países. Por estos motivos, la SEPAR ha considerado de interés actualizar las recomendaciones para el diagnóstico y el tratamiento de la EPOC. La presente actualización va dirigida a los profesionales de la salud que tratan a pacientes con EPOC, y tiene por objetivo servir de instrumento práctico para proporcionar a los pacientes una atención actualizada y adecuada, basada en las mejores evidencias científicas disponibles.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

Guía clínica SEPAR-ALAT de diagnóstico y tratamiento de la EPOC

Puntos clave: – La enfermedad pulmonar obstructiva cronica (EPOC) se caracteriza por la presencia de obstruccion cronica y poco reversible al flujo aereo, que se asocia a una reaccion inflamatoria anomala, principalmente frente al humo del tabaco. – La obstruccion al flujo aereo se define por la espirometria cuando el cociente volumen espiratorio forzado en el primer segundo/capacidad vital forzada (FEV1/FVC) tras broncodilatacion es menor de 0,7 (o por debajo del limite inferior de la normalidad en personas mayores de 60 anos). – La EPOC se asocia a inflamacion cronica con remodelacion que afecta a las vias aereas, parenquima y arterias pulmonares. – La gravedad de la EPOC se clasifica por el valor del FEV1 posbroncodilatador, estando tambien relacionada con la existencia de sintomas, atrapamiento aereo, insuficiencia respiratoria, afectacion sistemica y comorbilidad asociada. – La prevalencia de la EPOC en la poblacion adulta es del 9% en Espana y oscila entre el 8 y el 20% en Latinoamerica. La EPOC representa la cuarta causa de muerte en Espana y en el mundo.

Respiratory symptoms in European animal farmers

Farmers are known to be at high risk for the development of occupational airway disease. The aim of this European study was to determine which airway symptoms predominate in different types of animal farmers (cattle, pigs, poultry, sheep) and to compare the prevalence of symptoms to the general population. A total of 6,156 randomly selected animal farmers in Denmark, Germany (Schleswig-Holstein, Niedersachsen), Switzerland, and Spain completed a questionnaire on respiratory symptoms and farming characteristics in 1995-1997. The prevalence of general respiratory symptoms was compared to the results of the European Community Respiratory Health Survey (ECRHS) obtained in the same regions. Pig farmers were at highest risk for the development of work-related symptoms. A significant dose-response relationship between daily hours worked inside animal houses and symptoms was established for pig and poultry farmers. Additionally, self-reported nasal allergies (odds ratio (95% confidence interval): 3.92 (3.26-4.71)) and nasal irritation during work (3.98 (3.35-4.73)) were shown to be associated with the development of chronic phlegm. The prevalence of wheezing, shortness of breath, asthma and nasal allergies was signficantly lower among all farmers in the age group 20-44 yrs than among the general population. However, the prevalence of usually bringing up phlegm in winter among farmers was significantly higher than in the general population (9.4 (8.3-10.5%) versus 7.5 (6.5-8.5%)). Individual factors have been shown to be related to the prevalence of chronic phlegm among farmers. Additionally, this study could support the hypothesis that farming could be negatively related to allergic diseases.

Microbiome Diversity in the Bronchial Tracts of Patients with Chronic Obstructive Pulmonary Disease

ABSTRACT Culture of bacteria from bronchial secretions in respiratory patients has low sensitivity and does not allow for complete assessment of microbial diversity across different bronchial compartments. In addition, a significant number of clinical studies are based on sputum samples, and it is not known to what extent they describe the real diversity of the mucosa. In order to identify previously unrecognized lower airway bacteria and to investigate the complexity and distribution of microbiota in patients with chronic obstructive pulmonary disease (COPD), we performed PCR amplification and pyrosequencing of the 16S rRNA gene in patients not showing signs or symptoms of infection. Four types of respiratory samples (sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa) were taken from each individual, obtaining on average >1,000 16S rRNA sequences per sample. The total number of genera per patient was >100, showing a high diversity, with Streptococcus, Prevotella, Moraxella, Haemophilus, Acinetobacter, Fusobacterium, and Neisseria being the most commonly identified. Sputum samples showed significantly lower diversity than the other three sample types. Lower-bronchial-tree samples, i.e., bronchoalveolar lavage and bronchial mucosa, showed a very similar bacterial compositions in contrast to sputum and bronchial aspirate samples. Thus, sputum and bronchial aspirate samples are upper bronchial tree samples that are not representative of the lower bronchial mucosa flora, and bronchoalveolar lavage samples showed the results closest to those for the bronchial mucosa. Our data confirm that the bronchial tree is not sterile in COPD patients and support the existence a different microbiota in the upper and lower compartments.

Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

Anti-Tissue Antibodies Are Related to Lung Function in Chronic Obstructive Pulmonary Disease

RATIONALE Chronic obstructive pulmonary disease (COPD) is a multicomponent disease. Autoimmunity can contribute to the pathogenesis of COPD. OBJECTIVES This study investigates the prevalence of circulating antinuclear antibodies (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in COPD and their relationship with several components of the disease. METHODS We determined lung function, the serum titers of ANA and AT by immunofluorescence, and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry in 328 patients with clinically stable COPD and in 67 healthy controls recruited in the PAC-COPD study. Multiple linear and logistic regression analysis was used to analyze results. MEASUREMENTS AND MAIN RESULTS The prevalence of abnormal ANA and AT titers was 34% and 26% in patients and 3% and 6% in controls, respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of patients with COPD and were independently associated with the severity of airflow limitation and gas transfer impairment (P < 0.05). Neither ANA or AT titers was related to body mass index, current smoking status, use of inhaled steroids, the Charlson index, or serum C-reactive protein values. CONCLUSIONS Between a quarter and a third of patients with clinically stable COPD present abnormal titers of circulating ANA and AT. The observed relationship between AT and lung function supports a role for autoimmunity in the pathogenesis of COPD.

Quality of life in severe chronic obstructive pulmonary disease: correlation with lung and muscle function

UNLABELLED Chronic obstructive pulmonary disease (COPD) patients suffer from significant impairment in quality of life (QL), but the variables related to this impairment are not well known. The aim of this study has been to identify physiological parameters related to QL in severe COPD patients undergoing long-term oxygen therapy. MATERIALS AND METHODS We studied 47 COPD patients using long-term oxygen therapy (43 men/four women, 65.17 SD 8.21 years, 3.17 SD 2.61 years on oxygen). The Nottingham Health Profile (NHP) and activities of daily living (ADL) questionnaire were used to measure QL. Subjective assessment of dyspnoea was performed using a visual analogue scale. The physiological parameters determined were lung function (spirometry, arterial blood gases, lung volumes and carbon monoxide diffusing capacity), muscle function (maximum inspiratory and expiratory pressures, deltoid muscle and handgrip strength), and nutrition status (tricipital skin fold and mid-arm muscle circumference). RESULTS High ADL (8.32 SD 6.97) and NHP scores (energy 63.3 SD 40.43, pain 35.11 SD 31.56, emotional reactions 43.03 SD 25.13, sleep 51.91 SD 32.75, social isolation 30.64 SD 26.98, physical mobility 49.73 SD 24.93) demonstrated clinically significant QL impairment in the severe COPD patients studied. Stepwise multiple regression analysis found a correlation between lung function and QL. Low FEV1% was associated with impairment in energy, physical mobility and social isolation NHP scores and ADL score (r = -0.3, P < 0.05). RV/TLC also correlated with ADL and social isolation scores (r = 0.3, P < 0.05). Lung function explained 39-45% of the variation in these QL dimensions. QL did not correlate with other lung function parameters, muscle function or nutrition status. CONCLUSION COPD patients using long-term oxygen suffer from severe QL impairment affecting not only energy and mobility but also emotional reactions, social isolation and sleep. Lung function is related to energy, mobility and social isolation dimensions, but muscle function is unrelated to QL in these patients.

Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer.

BackgroundConventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer.MethodsPatients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined.ResultsIn 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%).ConclusionsCell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.

Severity-Related Changes of Bronchial Microbiome in Chronic Obstructive Pulmonary Disease

ABSTRACT Bronchial colonization by potentially pathogenic microorganisms (PPMs) is often demonstrated in chronic obstructive pulmonary disease (COPD), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. The aim of the study was to determine changes in the bronchial microbiome of COPD associated with the severity of the disease. The bronchial microbiome of COPD patients was analyzed by 16S rRNA gene amplification and pyrosequencing in sputum samples obtained during stable disease. Seventeen COPD patients were studied (forced expiratory volume in the first second expressed as a percentage of the forced vital capacity [FEV1%] median, 35.0%; interquartile range [IQR], 31.5 to 52.0), providing a mean of 4,493 (standard deviation [SD], 2,598) sequences corresponding to 47 operational taxonomic units (OTUs) (SD, 17) at a 97% identity level. Patients were dichotomized according to their lung function as moderate to severe when their FEV1% values were over the median and as advanced when FEV1% values were lower. The most prevalent phyla in sputum were Proteobacteria (44%) and Firmicutes (16%), followed by Actinobacteria (13%). A greater microbial diversity was found in patients with moderate-to-severe disease, and alpha diversity showed a statistically significant decrease in patients with advanced disease when assessed by Shannon (ρ = 0.528; P = 0.029, Spearman correlation coefficient) and Chao1 (ρ = 0.53; P = 0.028, Spearman correlation coefficient) alpha-diversity indexes. The higher severity that characterizes advanced COPD is paralleled by a decrease in the diversity of the bronchial microbiome, with a loss of part of the resident flora that is replaced by a more restricted microbiota that includes PPMs.