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In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

The Smoking and the Diffuse Interstitial Lung Diseases (ILD) groups of ALAT and SEPAR collaborated in the preparation of this document.This document uses PICO methodology to answer various questions on the relationship between tobacco use and diffuse ILD.The main recommendations are: a) moderate level of evidence and strong recommendation to consider smoking as a risk factor for the development and/or modification of the progression of diffuse ILD; b) moderate level of evidence to identify an increase in mortality in diffuse ILD, irrespective of histologic pattern. Low evidence for ascribing it to smoking and strong recommendation for the early identification of patients with diffuse ILD. Further studies are needed to evaluate the effect of smoking cessation in patients with diffuse ILD; c) low level of evidence and weak recommendation for defining the impact of passive smoking in diffuse ILD; d) low level of evidence to demonstrate that smoking cessation improves the outcomes of patients diagnosed with diffuse ILD and strong recommendation to advise smoking cessation in smokers with diffuse ILD, and e) low level of evidence to support the clinical or epidemiological usefulness of active case finding for diffuse ILD in smoking cessation programs, and strong recommendation justifying the performance of spirometry in active case finding, based not on current smoking status, but on previous accumulated consumption, even in asymptomatic cases.

Interstitial lung diseases (ILD) and, in particular, idiopathic pulmonary fibrosis, may have a significant impact on patient survival. Recent studies highlight the need for palliative care (PC) in the management of ILD patients. The aim of this study was to determine the current situation of PC in patients in Spain.A 36-question survey addressing the main aspects of PC in ILD patients was designed. The survey was sent via email to all members of the Spanish Society of Pulmonology and Thoracic Surgery. Participation was voluntary.One hundred and sixty-four participants responded to the survey. Ninety-eight percent said they were interested in PC, 46% had received specific training, and 44% reported being responsible for PC in their ILD patients. Symptom control and end-of-life stage were the most frequent reasons for referral to PC teams. Regarding end-of-life, 78% reported consensual agreement with patients on the limitation of therapeutic efforts, 35% helped prepare an end-of-life advance directive, and 22% agreed on the place of death.Despite the well-known need for PC in patients with ILD and the notable interest of the survey participants in this subject, there are clear formative and organizational gaps that should be addressed to improve care in this area in ILD patients in Spain.

[EN] Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines., [ES] La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con mal pronóstico. Su incidencia ha aumentado en los últimos años, probablemente por la optimización de los métodos diagnósticos y el aumento en la esperanza de vida. En 2013 se publicó la normativa SEPAR sobre el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Desde entonces, se han publicado los resultados de ensayos clínicos y metaanálisis que han supuesto, con base en la evidencia científica, la introducción de pirfenidona y nintedanib en el tratamiento de la enfermedad. En 2015 se ha actualizado el consenso internacional de 2011, en el que se describen los cambios en las recomendaciones terapéuticas. Debido a ello cabía actualizar el apartado de la normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática. No se tratarán aspectos diagnósticos ni el tratamiento no farmacológico, ya que no se han producido cambios relevantes desde la normativa de 2013.

Interest in identifying the long-term harmful effects of atmospheric pollution on respiratory health, and concern about this issue, has prompted several studies, whose results have been published throughout this year. On the occasion of the Spanish Society of Pneumology and Thoracic Surgery's Year of the Environment, from the Section of Occupational and Environmental Respiratory Diseases, we review the advances made in the effects of atmospheric pollution on respiratory health and the actions undertaken by the Society. The main objective of the Society's Year of the Environment is to inform citizens in general and respiratory patients in particular of the benefits of breathing clean air. The first step in achieving this aim is education. The goal is to educate young people in lasting habits that promote a respectful attitude to the environment, inculcating them with the need for sustainable development through responsible energy consumption and reduction of the emission of pollutants. Informed citizens will demand public health policies aimed at maintaining the quality of the air we breathe from politicians. The website www.elaireesnuestro.com provides information and educational material on the subject.

The continued inhalation of contaminants present in the air that we breathe is a common cause of respiratory disease. Classically, this exposure-disease relationship has been proved in the workplace and as a cause of specific diseases such as pneumoconiosis and occupational asthma. However, there is increasing evidence indicating an association between occupational exposure and other more prevalent respiratory diseases such as Chronic Obstructive Pulmonary Disease and lung cancer. The effect of contamination is also observed outside the workplace. The air in cities can contribute to increasing the morbidity and mortality due to chronic respiratory diseases. Some articles published during the year 2009 that have a bearing on aspects associated with respiratory diseases of occupational or environmental origin are reviewed below.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment.

Resumen La proteinosis alveolar pulmonar (PAP) es una rara enfermedad que se caracteriza por la acumulacion en el alveolo pulmonar de un material lipoproteico derivado del surfactante alveolar, lo que provoca el consiguiente deterioro del intercambio gaseoso. Su patogenia esta relacionada con alteraciones en la capacidad fagocitica del macrofago alveolar. Desde hace pocos anos existe un nuevo tratamiento para la PAP consistente en la administracion de factor estimulante de colonias de granulocitos y macrofagos (GM-CSF) por via subcutanea. El tratamiento comunmente aceptado y que ha demostrado mayor eficacia en la PAP es el lavado pulmonar total. Una alternativa a este tratamiento es la administracion por via inhalada en aerosolterapia de este factor. La administracion del GM-CSF por via inhalada es segura y eficaz para el tratamiento de la PAP y supone una alternativa al tratamiento con lavado pulmonar total y GM-CSF por via subcutanea. Presentamos un caso de PAP tratada con GM-CSF por via inhalada y su evolucion clinica y funcional tras un ano de tratamiento.

We analyze changes in eosinophilic cationic protein (ECP) serum levels after treatment with intranasal corticoids. Fifty-three healthy individuals (control group) and 21 patients diagnosed of allergic rhinitis, with or without bronchial asthma, were enrolled at a time when they had only nasal symptoms. Data were collected from skin Prick tests, forced spirometry, methacholine challenge, and complete blood workups, including IgE measurement, eosinophil counts and ECP serum levels determined by immunofluorescence. The patients received intranasal budesonide at a dose of 200 micrograms/24 h. ECP levels and eosinophil counts were determined before (baseline levels) and during treatment (on days 21 and 60). We found significant differences (p < 0.01) in baseline ECP levels of the controls (9.34 +/- 5.76) and patients (16.47 +/- 15.28). These values were significantly lower than baseline 21 and 60 days after treatment, although the changes between days 21 and 60 were not significant. Eosinophil counts did not fall significantly. We also found that eosinophil counts and ECP levels were correlated (r = 0.53) at baseline but not after treatment (r = 0.25). No patient experienced bronchial symptoms during the study. We conclude that ECP serum levels in patients with symptoms of rhinitis are significantly higher than levels in non symptomatic individuals. These levels fall significantly, possibly due to intranasal corticoid treatment, although eosinophil counts remain constant. ECP levels can therefore be used to monitor inflammatory activity in patients with allergic rhinitis.

Chronic respiratory diseases often cause impairment in the functions and/or structure of the respiratory system, and impose limitations on different activities in the lives of persons who suffer them. In younger patients with an active working life, these limitations can cause problems in carrying out their normal work. Article 41 of the Spanish Constitution states that «the public authorities shall maintain a public Social Security system for all citizens guaranteeing adequate social assistance and benefits in situations of hardship». Within this framework is the assessment of fitness for work, as a dual-nature process (medico-legal) that aims to determine whether it is appropriate or not to recognise a person's right to receive benefits which replace the income that they no longer receive as they cannot carry out their work, due to loss of health. The role of the pulmonologist is essential in evaluating the diagnosis, treatment, prognosis and functional capacity of respiratory patients. These recommendations seek to bring the complex setting of fitness for work evaluation to pulmonologists and thoracic surgeons, providing action guidelines that allow them to advise their own patients about their incorporation into working life.

Para analizar la validez de parametros funcionales basales en la prediccion de la VE max obtenida en el esfuerzo en pacientes con enfermedad pulmonar obstructiva cronica (EPOC), estudiamos a 33 pacientes en situacion estable (FEV 1 43,6 ± 16,8%, FEV 1 /FVC% 48,4 ± 9,2, FRC 156,8 ± 32,7% y RV 212 ± 53,9%), dividiendolos posteriormente en 3 grupos atendiendo a la severidad de la afeccion (severa, moderada o leve) para observar si la prediccion de la ventilacion maxima mejoraba al incrementarse la obstruccion de las vias aereas (FEV 1 26,9 ± 4,9%, 40,2 ± 3,5% y 63,9 + 10%, respectivamente). Los enfermos fueron sometidos a pruebas de funcion pulmonar en reposo y posteriormente a un test de esfuerzo progresivo y maximo realizado mediante tapiz rodante. Observamos una mejor correlacion con VE max para RV, FEV 1 y FRC (r = -0,77, 0,75 y -0,74, respectivamente) apreciando una mejoria en esta relacion cuando considerabamos a los enfermos mas afectados, FEV 1 max se consiguio con mayor fiabilidad en ecuaciones que utilizaban conjuntamente FEV 1 y datos referentes al grado de insuflacion de los pacientes, RV o FRC (VEmax = 45,2 + 8,98 x FEV 1 – 5,07 x RV; r 2 = 0,72) que con aquellas basadas en FEV 1 aisladamente (VE max = 14,79 + 15,03 x FEV 1 ; r 2 = 0,56). Por tanto, de nuestros hallazgos podemos concluir que la limitacion ventilatoria al ejercicio en pacientes con EPOC queda mejor definida anadiendo al grado de obstruccion espiratoria parametros de insuflacion pulmonar, condicionantes de la mayor o menor eficacia muscular durante el esfuerzo. Esto es particularmente evidente en el grupo de enfermos mas severamente afectados, mientras que en el resto la relacion de la maxima ventilacion con los datos de funcion pulmonar fue menos satisfactoria.

We analyzed serum levels of eosinophilic cationic protein (ECP), one of the 4 main eosinophilic proteins; ECP is released from an activated cell and acts as a mediator of inflammation. Serum samples from 139 persons were studied prospectively. Fifty-three individuals from the general population provided the control group. Eighty-six consecutive patients were also studied: 69 with bronchial asthma and 17 with allergic rhinitis and no signs of asthma. The level of severity of disease was established in the asthmatics by the method proposed by Aas (Aas score), based on symptoms and medications received within the last year. We also classified these patients as having mild, moderate or severe asthma according to the latest criteria issued by the International Consensus for Diagnosis and Treatment of Asthma. Atopic status was estimated by skin Prick tests. ECP levels in the control group (9.34 +/- 5.76 micrograms/l) were significantly lower (p < 0.001) than those of the total population of patients (17.59 +/- 16.85 micrograms/l). The mean for patients with rhinitis was 14.76 +/- 10.94 micrograms/l, whereas it was 18.29 +/- 18 micrograms/l in the asthmatics; the levels for both groups were statistically different from that of the control group (p < 0.03 and p < 0.001, respectively). Levels by degrees of severity established at the time of revision and by sensitivity to allergens were also significantly different from the level of the control group, although the mean levels were low in the group of severely affected patients who had received treatment with inhaled corticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemos realizado un trabajo epidemiologico de tipo transversal, como parte de un estudio multicentrico europeo, con el objeto de estimar la prevalencia de sintomatologia respiratoria y aquella relacionada con el asma presente en los ultimos 12 meses en la ciudad de Sevilla. El estudio se realizo con una muestra de 4.000 personas de ambos sexos, con edades comprendidas entre 20 y 44 anos mediante el empleo de un cuestionario enviado por correo y posteriormente con el empleo de la entrevista por telefono. Analizamos el indice de respuestas obtenido en el muestreo por correo en el estudio epidemiologico sobre asma en nuestra zona, asi como la frecuencia de sintomatologia respiratoria y su distribucion por edad y sexo. El indice de respuestas fue de un 53,36%, siendo similar en ambos sexos. Presentaban algun tipo de sintoma respiratorio un 49% de los encuestados, siendo lo mas frecuente la existencia de ataques de tos nocturna (27,7%) y la presencia de sibilancias (22,2%). Sin embargo, su frecuencia era diferente en ambos sexos, siendo el primero de los sintomas mas frecuente en mujeres (p

Interest in identifying the long-term harmful effects of atmospheric pollution on respiratory health, and concern about this issue, has prompted several studies, whose results have been published throughout this year. On the occasion of the Spanish Society of Pneumology and Thoracic Surgery's Year of the Environment, from the Section of Occupational and Environmental Respiratory Diseases, we review the advances made in the effects of atmospheric pollution on respiratory health and the actions undertaken by the Society. The main objective of the Society's Year of the Environment is to inform citizens in general and respiratory patients in particular of the benefits of breathing clean air. The first step in achieving this aim is education. The goal is to educate young people in lasting habits that promote a respectful attitude to the environment, inculcating them with the need for sustainable development through responsible energy consumption and reduction of the emission of pollutants. Informed citizens will demand public health policies aimed at maintaining the quality of the air we breathe from politicians. The website www.elaireesnuestro.com provides information and educational material on the subject.

The continued inhalation of contaminants present in the air that we breathe is a common cause of respiratory disease. Classically, this exposure-disease relationship has been proved in the workplace and as a cause of specific diseases such as pneumoconiosis and occupational asthma. However, there is increasing evidence indicating an association between occupational exposure and other more prevalent respiratory diseases such as Chronic Obstructive Pulmonary Disease and lung cancer. The effect of contamination is also observed outside the workplace. The air in cities can contribute to increasing the morbidity and mortality due to chronic respiratory diseases. Some articles published during the year 2009 that have a bearing on aspects associated with respiratory diseases of occupational or environmental origin are reviewed below.

We analyze changes in eosinophilic cationic protein (ECP) serum levels after treatment with intranasal corticoids. Fifty-three healthy individuals (control group) and 21 patients diagnosed of allergic rhinitis, with or without bronchial asthma, were enrolled at a time when they had only nasal symptoms. Data were collected from skin Prick tests, forced spirometry, methacholine challenge, and complete blood workups, including IgE measurement, eosinophil counts and ECP serum levels determined by immunofluorescence. The patients received intranasal budesonide at a dose of 200 micrograms/24 h. ECP levels and eosinophil counts were determined before (baseline levels) and during treatment (on days 21 and 60). We found significant differences (p0.01) in baseline ECP levels of the controls (9.34 +/- 5.76) and patients (16.47 +/- 15.28). These values were significantly lower than baseline 21 and 60 days after treatment, although the changes between days 21 and 60 were not significant. Eosinophil counts did not fall significantly. We also found that eosinophil counts and ECP levels were correlated (r = 0.53) at baseline but not after treatment (r = 0.25). No patient experienced bronchial symptoms during the study. We conclude that ECP serum levels in patients with symptoms of rhinitis are significantly higher than levels in non symptomatic individuals. These levels fall significantly, possibly due to intranasal corticoid treatment, although eosinophil counts remain constant. ECP levels can therefore be used to monitor inflammatory activity in patients with allergic rhinitis.

To analyze the validity of baseline lung function parameters as predictors of maximal exercise ventilation (VEmax) in patients with chronic obstructive pulmonary disease (COPD), we studied 33 stable patients (FEV1 43.6 +/- 16.8%, FEV1/FVC% 48.4 +/- 9.2, FRC 156.8 +/- 32.7% and RV 212 +/- 53.9%). The sample was later divided into 3 groups based on severity of disease (severe, moderate or mild) in order to determine whether ability to predict VEmax increased with airways obstruction (FEV1 26.9 +/- 4.9%, 40.2 +/- 3.5% and 63.9 +/- 10%, respectively). The patients underwent lung function testing at rest and after a progressive stress test, with the maximal reading taken with the subject on a tread mill. We found greater correlation between VEmax and RV, FEV1 and FRC (r = -0.77, 0.75 and -0.74, respectively); the correlation was stronger in patients with severe COPD, in whom FEV1 was under 35% of the predicted value (r = -0.88, 0.753 and -0.83, respectively). Correlation decreased or disappeared with less functional impairment. Prediction of VEmax was more reliable with equations that employed FEV1 accompanied by data reflecting degree of insufflation, RV or FRC (VEmax = 45.2 +/- 8.98 x FEV1 - 5.07 x RV; r2 = 0.72) than with equations based on FEV1 alone (VEmax = 14.79 + 15.03 x FEV1; r2 = 0.56). We therefore conclude that ventilatory limitation during exercise in patients with COPD is better defined by considering parameters related to lung insufflation along with those reflecting degree of expiratory obstruction, given that the former affect the greater or lesser efficacy of muscles under stress.(ABSTRACT TRUNCATED AT 250 WORDS)

We analyzed serum levels of eosinophilic cationic protein (ECP), one of the 4 main eosinophilic proteins; ECP is released from an activated cell and acts as a mediator of inflammation. Serum samples from 139 persons were studied prospectively. Fifty-three individuals from the general population provided the control group. Eighty-six consecutive patients were also studied: 69 with bronchial asthma and 17 with allergic rhinitis and no signs of asthma. The level of severity of disease was established in the asthmatics by the method proposed by Aas (Aas score), based on symptoms and medications received within the last year. We also classified these patients as having mild, moderate or severe asthma according to the latest criteria issued by the International Consensus for Diagnosis and Treatment of Asthma. Atopic status was estimated by skin Prick tests. ECP levels in the control group (9.34 +/- 5.76 micrograms/l) were significantly lower (p0.001) than those of the total population of patients (17.59 +/- 16.85 micrograms/l). The mean for patients with rhinitis was 14.76 +/- 10.94 micrograms/l, whereas it was 18.29 +/- 18 micrograms/l in the asthmatics; the levels for both groups were statistically different from that of the control group (p0.03 and p0.001, respectively). Levels by degrees of severity established at the time of revision and by sensitivity to allergens were also significantly different from the level of the control group, although the mean levels were low in the group of severely affected patients who had received treatment with inhaled corticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper is a report of a cross-sectional epidemiological study that formed part of multicenter European project; the aim was to estimate the prevalence of respiratory symptoms and signs related to asthma over a period of 12 months in the city of Seville. A sample of 4,000 persons of both sexes, aged between 20 and 44 years old, was surveyed first by mail questionnaire and later by telephone interview. We analyzed the response index obtained with the mail survey for the epidemiological study of asthma in the area and for the frequency of respiratory symptoms and their distribution by age and sex. The response index was 53.36% and was similar for men and for women. Forty-nine percent reported at least one respiratory symptom, with nocturnal coughing attacks (27.7%) and wheezing (22.2%) being the most frequent. The frequency of these symptoms was different by sex, however, with the former more often reported by women (p0.02) and the latter by men (p0.001). We found that 14.9% of the population had rhinitis and that women reported this symptom more often (p0.02). Symptoms related to asthma were nocturnal attacks of breathlessness, the use of asthma medication and an asthma attack diagnosed by a physician within the last 12 months. With these criteria the estimated prevalence of asthma was 11.72%, a proportion that held steady for all age groups except the middle-aged and for both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)