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Background and objective: Forced vital capacity (FVC) less than 50% of predicted is one of the main parameters used for Non-Invasive Ventilation (NIV) initiation in Amyotrophic Lateral Sclerosis (ALS). Recent studies suggest that higher values of FVC could be considered as a threshold. The aim of this study is to evaluate whether early use of NIV improves the prognosis of ALS patients compared with standard initiation. Methods: This is a randomized, parallel, multicenter, open-label, controlled clinical trial, with recruitment at the ALS outpatient multidisciplinary units of six Spanish hospitals. Patients were included when their FVC reached the 75% threshold and were randomized by computer, stratifying by center in an allocation ratio of 1:1 to Early NIV (FVC below 75%) or Standard NIV (FVC below 50%) initiation. The primary outcome was time to death or tracheostomy. Trial registration number ClinicalTrials.gov: NCT01641965. Results: Between May 2012 and June 2014, 42 patients were randomized to two groups, 20 to Early NIV and 22 to Standard NIV initiation. We found differences in survival in favor of the intervention group: an incidence of mortality (2.68 [1.87–5.50] vs. 3.33 [1.34–4.80] person-months) and a median survival (25.2 vs. 19.4 months), although without reaching statistical significance (p = 0.267). Conclusions: This trial did not reach the primary endpoint of survival; nevertheless, it is the first Randomized Controlled Trial (RCT) to demonstrate the benefits of early NIV in slowing the decline of respiratory muscle strength and reducing adverse events. Although not all the results reached statistical significance, all the analyzed data favor early NIV. In addition, this study demonstrates good tolerance and compliance with early NIV without quality of sleep impairment. These data reinforce the early respiratory evaluation of ALS patients and NIV initiation with an FVC of around 75%.

Summary Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function. Methods The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60–90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178 ) has also been completed, but will be reported separately. Findings Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5–51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4–48·1) weeks. Change from baseline in supine SVC at 12 weeks was –6·73% with levosimendan and –6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI –2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI –15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis. Interpretation Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation. Funding Orion Corporation.

Resumen El soporte respiratorio no invasivo (SRNI) comprende 2 modalidades de tratamiento, la ventilacion mecanica no invasiva (VMNI) y la terapia de alto flujo con canulas nasales (TAFCN) que se aplican en pacientes adultos, pediatricos y neonatales con insuficiencia respiratoria aguda (IRA). Sin embargo, el grado de acuerdo entre las distintas especialidades sobre el beneficio de estas tecnicas en diferentes escenarios clinicos es controvertido. El objetivo del presente consenso fue elaborar una serie de recomendaciones de buena practica clinica para la aplicacion de soporte no invasivo en pacientes con IRA, avaladas por todas las sociedades cientificas involucradas en el manejo del paciente adulto y pediatrico/neonatal con IRA. Para ello se contacto con las diferentes sociedades implicadas, quienes designaron a su vez a un grupo de 26 profesionales con suficiente experiencia en su aplicacion. Se realizaron 3 reuniones presenciales para consensuar las recomendaciones (hasta un total de 71) fundamentadas en la revision de la literatura y en la actualizacion de la evidencia disponible en relacion con 3 categorias: indicaciones, monitorizacion y seguimiento del SRNI. Finalmente, se procedio a votacion telematica de cada una de las recomendaciones, por parte de los expertos de cada sociedad cientifica implicada. Para la clasificacion del grado de acuerdo se opto por un sistema analogico de clasificacion facil e intuitivo de usar, y que expresara con claridad si el procedimiento relacionado con el SRNI debia hacerse, podia hacerse o no debia hacerse.

Purpose Multidisciplinary care has become the preferred model of care for patients with amyotrophic lateral sclerosis (ALS). It is assumed that the sum of interventions associated with this approach has a positive effect on survival. The objective of the study was to evaluate the impact of a multidisciplinary care approach on the survival of patients with ALS. Patients and methods We performed a retrospective review of prospectively collected data in a tertiary referral center in Spain. Participants were patients with definite or probable ALS managed in a multidisciplinary care program. We compared demographic and survival data of patients with definite or probable ALS treated in a referral center without and with implementation of a multidisciplinary care program. We performed time-dependent multivariate survival analysis of the use of noninvasive mechanical ventilation (NIMV) and gastrostomy. Results We evaluated 398 consecutive patients, of whom 54 were treated by a general neurologist and 344 were treated in the multidisciplinary care clinic. Patients receiving multidisciplinary care were older (62 vs 58 years), tended to have bulbar onset disease (30% vs 17.7%), and were more likely to receive riluzole (88.7% vs 29.6%, p 0.001), and nutrition via gastrostomy (32.3% vs 3.7%, p

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) progression is variable and affects several disease domains, including decline in lung function, exercise capacity, muscle strength, and health status as well as changes in body composition. We aimed to assess the longitudinal association of physical activity (PA) with these a priori selected components of disease progression. METHODS: We studied 114 COPD patients from the PAC-COPD cohort (94% male, mean [SD], 70 yr [8 yr] of age, 54 [16] forced expiratory volume in 1 s % predicted) at baseline and 2.6 yr (0.6 yr) later. Baseline PA was assessed by accelerometry. Multivariable general linear models were built to assess the association between PA and changes in lung function, functional exercise capacity, muscle strength, health status, and body composition. All models were adjusted for confounders and the respective baseline value of each measure. RESULTS: Per each 1000 steps higher baseline PA, forced expiratory volume in 1 s declined 7 mL less (P < 0.01), forced vital capacity 9 mL less (P = 0.03) and carbon monoxide diffusing capacity 0.10 mL·min·mm Hg less (P = 0.04), while the St George's Respiratory Questionnaire symptom domain deteriorated 0.4 points less (P = 0.03), per year follow-up. Physical activity was not associated with changes in functional exercise capacity, muscle strength, other domains of health status or body composition. CONCLUSIONS: Higher PA is associated with attenuated decline in lung function and reduced health status (symptoms domain) deterioration in moderate-to-very severe COPD patients. ispartof: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE vol:51 issue:5 pages:833-840 ispartof: location:United States status: published

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analogue classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied. (C) 2020 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

The PAC-COPD Study is funded by grants from Fondo de Investigacion Sanitaria (FIS PI020541), Ministry of Health, Spain; Agencia d’Avaluacio de Tecnologia i Recerca Mediques (AATRM 035/20/02), Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2002/137); Catalan Foundation of Pneumology (FUCAP 2003 Beca Maria Rava); Red RESPIRA (RTIC C03/11); Red RCESP (RTIC C03/09), Fondo de Investigacion Sanitaria (PI052486); Fondo de Investigacion Sanitaria (PI052302); Fundacio La Marato de TV3 (num. 041110); DURSI (2005SGR00392); and unrestricted educational grants from Novartis Farmaceutica, Spain, and AstraZeneca Farmaceutica, Spain. CIBERESP and CIBERES are funded by the Instituto de Salud Carlos III, Ministry of Health, Spain.

Objectives: To analyse the evolution and survival of the Myotonic Distrophy (MD) patients on treatment with non-invasive ventilation (NIV). Methods: Retrospective study including MD patients who started NIV in 1995-2016. Demographic and clinical data have been analysed, as well as the cause of initiating NIV and blood gases and pulmonary function in that moment. Gasometric evolution, comorbidity, mortality causes and survival have been analysed. Diferences in survival depending of the form of onset NIV (in the context of acute ventilatory failure or electively) have been also analysed. Analysis of survival was undertaken using the Kaplan-Meier method and comparison between groups with the long rank test. Results: The sample included 80 patients. The clinical situation at the start on NIV was: 46±15 years, 49% men, BMI 31±6, PaO2 65±11mmHg, PaCO2 52±8 mmHg, FVC 1762 ±737ml, bulbar involvement (33%). 34% began the ventilation in an acute situation. The most frequent comorbidity was cardiac (56% arrhythmias, 34% with pacemaker). During the follow-up, 6 patients (7%) abandoned the NIV and 28 (35%) died. The leading cause of death was respiratory insufficiency (31%). The median of survival was 121 ± 11 months (Kaplan-Meyer). Patients who started acute NIV had a worse survival in comparison with patients who started NIV electively (93 ± 40 months vs 186 ± 35 months, log rank 6,64 p=0,01). Conclusions: Survival probability at 10 years of initiating the ventilation is 50%. Those patients who begin ventilation in an acute situation present the worst survival. These results confirm the necessity of an early detection of the respiratory failure and the beginning of NIV in an elective way.

Unidad Funcional Interdisciplinaria Sociosanitaria (UFISS) Respiratoria, Hospital de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain Servicio de Respiratorio, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Unidad Sueno y Ventilacion, S. Respiratorio, Hospital Universitario de Alava, Alava, Spain Equipo de Soporte de Cuidados Paliativos, Hospital Universitario de Alava, Alava, Spain Servicio de Neumologia, Hospital San Pedro de Alcantara, Caceres, CIBERES, ISCIII, Madrid, Spain Servicio de Respiratorio, Hospital de San Carlos, Madrid, Spain Complejo Hospitalario Universitario A Coruna, CHUAC, A Coruna, Spain Unidad de Cuidados Respiratorios, Servicio de Neumologia, Hospital Clinico Universitario de Valencia, Valencia, Spain Unidad Medico-Quirurgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocio, Sevilla, Spain downloaded from http://www.archbronconeumol.org, day 16/05/2016. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation.Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models.213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV.In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Transcutaneous carbon dioxide (P(tcCO2)) monitoring is being used increasingly to assess acute respiratory failure. However, there are conflicting findings concerning its reliability when evaluating patients with high levels of P(aCO2). Our study evaluates the accuracy of this method in subjects with respiratory failure according to the severity of hypercapnia.We included subjects with respiratory failure, admitted to a respiratory intermediate care unit, who required arterial blood gas analysis. Simultaneously, P(tcCO2) was measured using a digital monitor. Relations between P(aCO2) and P(tcCO2) were assessed by the Pearson correlation coefficient. Bland-Altman analysis was used to test data dispersion, and an analysis of variance test was used to compare the differences between P(aCO2) and the corresponding P(tcCO2) at different levels (level 1,50 mm Hg; level 2, 50-60 mm Hg; level 3,60 mm Hg).Eighty-one subjects were analyzed. The main diagnosis was COPD exacerbation (45%). P(tcCO2) correlated well with P(aCO2) (r2 = 0.93, P.001). Bland-Altman analysis showed a mean P(aCO2) - P(tcCO2) difference of 4.9 ± 4.4 with 95% limits of agreement ranging from -3.6 to 13.4. The difference between variables increased in line with P(aCO2) severity: level 1, 1.7 ± 3.2 mm Hg; level 2, 3.7 ± 2.8; level 3, 6.8 ± 4.7 (analysis of variance, P.001).Our study showed an acceptable agreement of P(tcCO2) monitoring with arterial blood gas analysis. However, we should consider that P(tcCO2) underestimates P(aCO2) levels, and its accuracy depends on the level of hypercapnia, so this method would not be suitable for acute patients with severe hypercapnia.

Background: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. Methods: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH >= 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. (Continued on next page) Results: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 +/- 7.2 and 19 +/- 5.8 for the ACPE patients (p < 0.05), 20 +/- 5.7 and 19 +/- 5.1 for the COPD patients (p < 0.01) and 18 +/- 5.9 and 17 +/- 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 +/- 22 and 70 +/- 15 in the ACPE patients (p < 0.001), 87 +/- 21 and 76 +/- 14 in the COPD patients, and 83 +/- 17 and 74 +/- 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 +/- 3.1 vs. 3.6 +/- 2.5, NS; COPD, 5.1 +/- 3 vs. 3.6 +/- 2.1, p < 0.001; and OHS, 4.3 +/- 2.6 vs. 3.7 +/- 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. Conclusions: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH, Spanish Respiratory Foundation, 2011 (FEPAR)

Introduccion Los pacientes con enfermedad pulmonar obstructiva cronica (EPOC) se caracterizan por una actividad fisica limitada. Sorprendentemente, apenas se dispone de investigacion sobre los cuestionarios para medir la actividad fisica en la EPOC. El objetivo del presente estudio fue validar el cuestionario Yale Physical Activity Survey en pacientes con EPOC. Metodos Un total de 172 pacientes de 8 hospitales universitarios espanoles usaron un acelerometro (SenseWear®PrO2Armband) durante 8 dias y contestaron el cuestionario. Los analisis estadisticos de comparacion de ambos instrumentos incluyeron: a) correlacion de Spearman; b) coeficiente de correlacion intraclase (CCI) y graficos de Bland-Altman; c) distribucion de las medidas del acelerometro segun los terciles del cuestionario, y d) la curva receiver operating characteristic (ROC) para detectar a los pacientes sedentarios. Resultados El 94% de los participantes eran hombres, el 28% eran fumadores y el 7% eran trabajadores activos; la edad media (±DE) fue de 70 (8) anos, el volumen espiratorio medio en el primer segundo (VEMS) posbroncodilatador fue de 52 (15) como porcentaje del valor de referencia, y la mediana (p25-p75) de pasos fue de 5.702 (3.273-9.253) pasos/dia. Las correlaciones de Spearman fueron debiles o moderadas (desde 0,29 hasta 0,52, todas las p

Puntos clave : El objetivo fundamental de la oxigenoterapia es evitar la hipoxia tisular. La hipoxemia es una alteracion grave con consecuencias para todo el organismo por lo que ante su sospecha clinica se debe administrar oxigeno precozmente. El principal efecto secundario de la oxigenoterapia en situacion aguda es la retencion de CO2 con riesgo de acidosis respiratoria y coma en pacientes con insuficiencia respiratoria hipercapnica. El objetivo de la oxigenoterapia en situacion aguda en pacientes con sospecha de insuficiencia respiratoria hipercapnica es alcanzar una SaO2 entre el 88 y el 92%. No existen datos suficientes que apoyen la indicacion sistematica de oxigeno en el ictus ni en el infarto agudo de miocardio en ausencia de hipoxemia. ? La forma de administracion de oxigeno mas utilizada en situacion aguda es la mascara con efecto Ventouri. La forma de administracion de oxigeno mas utilizada en la oxigenoterapia cronica domiciliaria son las gafas o canulas nasales. La oxigenoterapia domiciliaria debe indicarse en pacientes con enfermedad pulmonar obstructiva cronica con hipoxemia (PaO2 60 mmHg con manifestaciones sistemicas) cronica. La fuente de suministro de oxigeno mas utilizada en la oxigenoterapia domiciliaria es el concentrador. La administracion de oxigeno no ha demostrado efectos beneficiosos como tratamiento sintomatico de la disnea en pacientes sin hipoxemia. La oxigenoterapia se define como la administracion de aire enriquecido...

Background: Chronic obstructive pulmonary disease (COPD) patients are very sensitive to changes in pulmonary mechanics and central ventilation control during sleep and may develop significant gas exchange alterations with increased hypoxemia and hypercapnia. Oxygen therapy improves nocturnal desaturation but can worsen hypoventilation. Objectives: To analyze the prevalence of nocturnal hypoventilation (NHV) in hypercapnic COPD patients and to determine predictive factors for this phenomenon. Methods: This was a prospective multicenter study which enrolled 80 clinically stable COPD patients with hypercapnic respiratory failure who fulfilled the conventional criteria for long-term oxygen therapy (LTOT). All patients had undergone pulmonary function testing, blood gas analysis, and respiratory polygraphy. Arterial blood gas samples were obtained while patients were awake and during sleep. NHV was considered when an increase in PaCO2 >10 mm Hg was observed in any nocturnal arterial blood gas sample as compared to the awake levels. Results: Seventeen patients (21%) developed NHV. NHV was associated with the values of BMI, hemoglobin, hematocrits, DLCO, and PaO2 reached after oxygen administration. In the logistic regression analysis BMI (OR 1.26, 95% CI 1.068–1.481; p = 0.006) and the diurnal increase of PaO2 after O2 (OR 0.89, 95% CI 0.807–0.972; p = 0.010) were the variables that best discriminated with a sensitivity of 82% and a specificity of 78%. Conclusions: NHV is a relatively common finding in stable hypercapnic COPD patients undergoing LTOT and it is related to a higher BMI and lower PaO2 after oxygen administration.

Resumen La definicion funcional de la enfermedad pulmonar obstructiva cronica (EPOC), basada en la limitacion al flujo aereo, ha predominado durante largo tiempo en el ambito de la neumologia. Sin embargo, ha surgido una nueva perspectiva que establece que en la EPOC tiene lugar una compleja variedad de manifestaciones celulares, organicas, funcionales y clinicas, y se ha incrementado el interes por desentranar la heterogeneidad fenotipica de dicha enfermedad. La presente revision se basa en la opinion de unos autores que tienen una amplia experiencia en la investigacion de los diversos aspectos de la EPOC. La revision parte de la base de que el conocimiento actual sobre la fisiopatologia y el cuadro clinico de la EPOC permite clasificar la informacion fenotipica en funcion de las siguientes dimensiones: sintomas respiratorios y estado de salud, exacerbaciones agudas, funcion pulmonar, cambios estructurales, inflamacion local y sistemica, y efectos sistemicos. Se han identificado 26 rasgos fenotipicos que se han asignado a alguna de las 6 dimensiones. Para cada dimension se proporciona un resumen de la mejor evidencia sobre la relacion existente entre los rasgos fenotipicos —en concreto, entre aquellos que corresponden a diferentes dimensiones— y sobre la relacion entre dichos rasgos y las manifestaciones relevantes en la evolucion natural de la EPOC. Toda la informacion se ha organizado graficamente en una matriz fenotipica donde cada celda que representa un par de rasgos fenotipicos esta vinculada a referencias bibliograficas relevantes. La informacion podria ayudar a comprender mejor la heterogeneidad de los fenotipos de la EPOC y a planificar estudios futuros sobre aspectos que todavia no se han investigado.

Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD.We measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline.Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (-27.4 ± 42.5, -24.9 ± 36.5 and -13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (β = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (β = -14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change.IC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions.

Objective Our objective was to compare the sublingual administration and the vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion. Design We used an open, multicenter, randomized trial. Locations We conducted the study in four clinics (in Valencia, Castello, Murcia and Murcia Capital) in Spain. Participants A total of 1424 healthy pregnant women with amenorrhea of ≤84 days who voluntarily decided to terminate their pregnancy participated in the study. Methods Women were randomly assigned to receive a single dose of 400 μg of misoprostol either sublingually or vaginally 1–3 h before aspiration. Outcome Measures The outcome measures assessed were cervical dilation before surgery and surgical time needed for aspiration. The incidence of side effects, such as nausea, vomiting, diarrhea, fever/chills and paresthesia, was evaluated. Results The mean cervical dilation achieved was 6.8±0.8 and 6.7±0.9 mm for the sublingual and vaginal groups, respectively. The mean surgical time was 7.0±2.8 and 7.4±2.5 min for the sublingual and vaginal groups, respectively. Nausea, vomiting and diarrhea were more frequent in the sublingual group. Conclusions Both regimens had equal efficacy; however, the sublingual route caused more side effects.

Study objectives: To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Design and setting: Retrospective study in a tertiary care referral center. Patients: HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). Results: In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p 0.001) and tracheal ventilation (p 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p 0.0002). Conclusions: Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages. (CHEST 2005; 127:2132–2138)

We have previously reported an apparently paradoxical association between medical care related factors and an increased risk of chronic obstructive pulmonary disease (COPD) re-hospitalisation, in a cohort of 346 COPD subjects from Barcelona, Spain. Confounding by severity or by indication is a plausible explanation. We tested the confounding effect of severity-related variables on these paradoxical associations. Forced expiratory volume in one second (FEV 1 ), arterial oxygen pressure ( P O 2 ) and previous COPD admissions were associated with: (1) the presence of medical care related factors, and (2) re-admission during follow-up. Risks of re-admission associated with most of the medical care related factors were reduced after adjustment for the severity variables. The risk associated with long-term oxygen therapy use changed from a crude OR of 2.36 (95% CI: 1.79–3.11) to an adjusted OR of 1.38 (0.95–2.00), while that associated with anticholinergics use varied from 3.52 (2.37–5.21) to 2.10 (1.32–3.36)). We concluded that the excess risk of COPD re-admission associated with medical care related factors might be partially due to confounding by indication. Residual confounding may still account for part of the remaining excess risk. True adverse effects of some pharmacological treatments cannot be excluded.

La esclerosis lateral amiotrofica (ELA) es una enfer­ medad neurodegenerativa de etiologia desconocida, que se caracteriza por la perdida progresiva de neuronas motoras del cortex cerebral, tronco del encefalo y me­ dula espinal1. Se afectan tanto las neuronas motoras in­ feriores, lo que conduce a debilidad, atrofia y fascicula­ ciones de toda la musculatura voluntaria, como las superiores, lo que provoca espasticidad e hiperreflexia2. Es la mas frecuente de las enfermedades de neuronas motoras, con una incidencia anual aproximada de 2­ 3/100.000 habitantes, que aumenta con la edad, rara­ mente aparece antes de los 40 anos y es mas elevada en varones3. La supervivencia oscila entre 3 y 5 anos, aunque un 10% de los pacientes pueden vivir hasta 10 anos4, y la muerte se relaciona en la mayoria de los casos con insu­ ficiencia respiratoria. Aunque se han descrito algunos casos en los que la insuficiencia respiratoria aguda por afeccion diafragmatica es la primera manifestacion de la ELA5, lo mas frecuente es que la afeccion de la mus­ culatura respiratoria aparezca en fases avanzadas de la enfermedad, por lo que los sintomas respiratorios, como la disnea de esfuerzo, intolerancia al decubito, hiper­ somnolencia o cefalea matutina, pueden pasar inadver­ tidos en el paciente con importante discapacidad. Por otro lado, datos objetivos como las alteraciones gaso­ metricas aparecen de forma muy tardia en la evolucion respiratoria y, por tanto, tienen escasa relevancia en el manejo de estos pacientes6. En los ultimos anos existen evidencias crecientes de que la ventilacion no invasiva (VNI) mejora tanto la supervivencia7,8 como la calidad de vida de estos pacientes9, por lo que supone uno de los pilares basicos del tratamiento, ya que no se dispone de terapeutica eficaz hasta la fecha. Asi, el estudio de la funcion de la musculatura respiratoria y la deteccion temprana de las alteraciones ventilatorias es fundamen­ tales en el seguimiento clinico de estos pacientes ante

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 ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes 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 ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 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'

Study objectives To analyze the influence of ahospital-based home-care program (HCP) on the management of patientswith COPD receiving long-term oxygen therapy. Design andsetting Randomized, controlled study in a 1,000-bed universityhospital. Intervention The HCP applied to patients inthe intervention group (HCP group) consisted of a monthly telephonecall, home visits every 3 months, and home or hospital visits on ademand basis. Patients in the control group were given conventionalmedical care. Measurements Pulmonary function data, gas exchange, use of hospital resources (emergency department visits, admissions, and hospital stay) and the cost of medical assistance wereinvestigated in both groups before and after 1 year of study. Qualityof life was analyzed using the chronic respiratory questionnaire in thefirst 40 consecutive patients included in the study. Survivalthroughout the study was also assessed. Results Onehundred twenty-two patients were enrolled in the study, and 94 patients(46 in the HCP group and 48 in the control group) completed the 1-yearfollow-up period: 83 patients (88%) were men, and mean (± SD)age was 68 ± 8 years. During the follow-up period, there was ahighly significant decrease in the mean number of emergency departmentvisits (0.45 ± 0.83 vs 1.58 ± 1.96; p = 0.0001) and also asignificant decrease in hospital admissions (0.5 ± 0.86 vs1.29 ± 1.7; p = 0.001) and days of hospital stay (7.43 ± 15.6vs 18.2 ± 24.5; p = 0.01) in the HCP group. Patients in theintervention group required a total of 221 home visits (mean perpatient, 4.8 ± 0.8) and 69 hospital visits (mean per patient, 1.5 ± 1.07). In spite of the cost of the program, cost analysisshowed a total saving of 8.1 million pesetas ($46,823) in the HCPgroup, mainly due to a decrease in the use of hospital resources. Therewas no difference in pulmonary function, gas exchange, quality of life, and survival between the two groups. Conclusions Hospital-based home care is an effective alternative to hospitaladmission. It reduces the use of hospital resources and the cost ofhealth care.

El objetivo de este estudio ha sido determinar la utilidad de la visita domiciliaria en el seguimiento y valoracion del uso apropiado de la oxigenoterapia domiciliaria, considerando este como la concurrencia de todas las circunstancias (indicacion correcta, correccion de hipoxemia y cumplimiento de la prescripcion) necesarias para esperar beneficios de la oxigenoterapia domiciliaria. Se incluyen todos los pacientes residentes en L’Hospitalet de Llobregat (Barcelona) que, en junio de 1994, disponen de oxigenoterapia domiciliaria, a los que se realiza una visita domiciliaria durante la que se lleva a cabo una entrevista, espirometria, determinacion de CO en aire espirado y pulsioximetria. En caso de que tras la visita domiciliaria la indicacion de oxigenoterapia domiciliaria no se considere correcta, el paciente es remitido a la consulta hospitalaria para revalorar la indicacion. Se han visitado en el domicilio 128 pacientes (un 74% de varones) con una edad media de 68 anos, comprobando un uso adecuado de la oxigenoterapia domiciliaria solo en el 26% de los pacientes. La indicacion de oxigenoterapia domiciliaria se considero estrictamente correcta en 73 casos (49%), en 13 se comprueba la persistencia del habito tabaquico; de los 60 restantes, se observa una correccion de la hipoxemia con la oxigenoterapia en 46 y de estos solo 33 cumplen correctamente la prescripcion. Respecto al seguimiento de la oxigenoterapia domiciliaria, la visita domiciliaria combinada con el control hospitalario ha permitido suprimir la oxigenoterapia en 20 pacientes en los que la indicacion era incorrecta asi como introducir cambios en las fuentes de suministro de oxigeno en 16 pacientes portadores de bombona: 14 inician concentrador y dos oxigeno liquido. Las revisiones periodicas son imprescindibles para optimizar el tratamiento con oxigenoterapia domiciliaria. La visita domiciliaria es un buen instrumento para mejorar el seguimiento, ya que permite realizar una valoracion del paciente en la situacion real de uso del tratamiento y es un metodo de control muy bien aceptado por el paciente.

The present study aims to describe the pattern of physical activity and the frequency, duration and intensity of physical activity bouts in patients with chronic obstructive pulmonary disease (COPD), to assess how these patterns differ according to COPD severity, and to explore whether these patients meet the general guidelines for physical activity for older adults. 177 patients (94% male, mean±sd age 71±8 years and forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro2 Armband accelerometer for eight consecutive days. Physical activity bouts were defined as periods of ≥10 min above 1.5 metabolic equivalent tasks and classified according to their median intensity. Patients engaged in activity a median of 153 min·day−1 and 57% of that time was spent in bouts. Median frequencies of bouts per day were four and three for all and moderate-to-vigorous intensities, respectively. With increasing COPD severity, time in physical activity, proportion of time in bouts and frequency of bouts decreased. 61% of patients fulfilled the recommended physical activity guidelines. In conclusion, COPD patients of all spirometric severity stages engage in physical activity bouts of moderate-to-vigorous intensities. Patients with severe and very severe COPD perform their daily activities in fewer and shorter bouts than those in mild and moderate stages.

Between 1984 and 1993 we performed 2105 laser treatments in 1210 patients: 52% of treatments were done for malignant pathology, 45% for benign tracheal stenoses and 3% were in a miscellaneous group. The procedure was carried out with a rigid bronchoscope under general anaesthesia. In patients with malignant tumors, it is a good palliative treatment—safe, well tolerated and with immediate results; it can be repeated as many times as needed with and is well accepted by the patient. In patients without tumors, this method avoids emergency tracheotomies. The long term results are now under evaluation.

Background Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins. Methods Whole exome sequencing analysis was carried out in a large U.S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy. Results A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U.S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin. Conclusions Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission. Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52 ± 16% predicted) 3 months after discharge. Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking. We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.

Background Patients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity. Methods 172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear®Pro2Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland-Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients. Results 94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV1 was 52 (15)% predicted, and median (p25-p75) steps taken was 5,702 (3,273-9,253) steps per day−1. Spearman correlations were low to moderate (from 0.29 to 0.52, all P < .001). ICCs showed weak agreement (from 0.34 to 0.40, all P < .001). A wide variability in agreement was observed in the Bland-Altman plots. Significant differences in accelerometer measurements were found according to questionnaire tertiles (all P < .001). The area under the ROC for identifying sedentarism was 0.71 (95% CI: 0.63-0.79). Conclusions The Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered a screening tool to identify patients at risk for sedentarism.

UNLABELLED This study shows the risks and benefits of increasing the nocturnal oxygen flow in hypercapnic COPD patients undergoing LTOT, as recommended by some COPD treatment guidelines to avoid nocturnal desaturation. BACKGROUND AND OBJECTIVE Several COPD treatment guidelines recommend increasing oxygen flow during sleep to avoid nocturnal desaturation. However, such an increase could have deleterious clinical and gas exchange effects. The objective of this study was to evaluate short-term gas exchange alterations produced by increasing the nocturnal oxygen flow rate. METHODS Thirty-eight COPD patients with chronic hypercapnic respiratory failure were evaluated. In a cross-over study, patients were randomly assigned to receive the daytime oxygen flow rate on one night and an additional litre on the alternate night. Nocturnal pulse oximetry and arterial blood gases at awakening were measured, in each patient, on two consecutive days. RESULTS The administration of 1 L more oxygen during the night resulted in improved parameters of nocturnal oxygenation (oxygen pulse oximetry saturation-SpO2; percentage of sleep time spent at SpO2

BACKGROUND: This study describes the characteristics of a large sample of patients hospitalised for the first time for a chronic obstructive pulmonary disease (COPD) exacerbation. METHODS: All subjects first admitted for a COPD exacerbation to nine teaching Spanish hospitals during January 2004-March 2006, were eligible. COPD diagnosis was confirmed by spirometry under stability. At admission, sociodemographic data, lifestyle, previous treatment and diagnosis of respiratory disease, lung function and Charlson index of co-morbidity were collected. A comprehensive assessment, including dyspnea, lung function, six-minute walking test, and St. George's Respiratory Questionnaire (SGRQ), was completed 3 months after admission, during a clinically stable disease period. RESULTS: Three-hundred and forty-two patients (57% of the eligible) participated in the study: 93% males, mean (SD) age 68 (9) years, 42% current smokers, 50% two or more co-morbidities, 54% mild-to-moderate dyspnea, post-bronchodilator FEV(1) 52 (16)% of predicted (54% mild-to-moderate COPD in ATS/ERS stages), 6-min walking distance 440 m, total SGRQ score 37 (18), and 36% not report respiratory disease. The absence of a previous COPD diagnosis, positive bronchodilator test, female gender, older age, higher DLco and higher BMI were independently associated with less severe COPD. CONCLUSIONS: We show that the patients admitted after presenting with their first COPD exacerbation have a wide range of severity, with a large proportion of patients in the less advanced COPD stages. The PAC-COPD study is funded by grants from Fondo de Investigación Sanitaria (FIS PI020541), Ministry of Health, Spain; Agència d’Avaluació de Tecnologia i Recerca Mèdiques (AATRM 035/20/02), Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2002/137); Catalan Foundation of Pneumology (FUCAP 2003 Beca Marià Ravà); Red RESPIRA (RTIC C03/11); Red RCESP (RTICC03/09); Fondo de Investigación Sanitaria (PI052486); Fondo de Investigación Sanitaria (PI052302); Fundació La Marató de TV3 (num. 041110); Novartis Farmacèutica, Spain. CIBERESP and CIBERES are funded by the Instituto de Salud Carlos III, Ministry of Health, Spain. Judith Garcia Aymerich has a researcher contract from the Instituto de Salud Carlos III (CP05/00118), Ministry of Health, Spain. Jordi de Batlle had a predoctoral fellowship from the Instituto de Salud Carlos III (FI05/01022), Ministry of Health, Spain.

Background: The mechanisms underlying the benefits of regular physical activity in the evolution of COPD have not been established. Our objective was to assess the relationship between regular physical activity and the clinical and functional characteristics of COPD. Methods: Three hundred forty-one patients were hospitalized for the first time because of a COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by spirometry under stable conditions. Physical activity before the first COPD hospitalization was measured using the Yale questionnaire. The following outcome variables were studied under stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and peripheral muscle strength, bronchial colonization, and systemic inflammation. Results: The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and the mean postbronchodilator FEV1 was 52% predicted (SD, 16% predicted). Multivariate linear regression models were built separately for each outcome variable and adjusted for potential confounders (including remaining outcomes if appropriate). When patients with the lowest quartile of physical activity were compared to patients in the other quartiles, physical activity was associated with significantly higher diffusing capacity of the lung for carbon monoxide (DLCO) [change in the second, third, and fourth quartiles of physical activity, compared with first quartile (+ 6%, + 6%, and + 9% predicted, respectively; p = 0.012 [for trend])], expiratory muscle strength (maximal expiratory pressure [PEmax]) [+ 7%, + 5%, and + 9% predicted, respectively; p = 0.081], 6-min walking distance (6MWD) [+ 40, + 41, and + 45 m, respectively; p = 0.006 (for trend)], and maximal oxygen uptake (V̇O2peak) [+ 55, + 185, and + 81 mL/min, respectively; p = 0.110 (for trend)]. Similarly, physical activity reduced the risk of having high levels of circulating tumor necrosis factor α (odds ratio, 0.78, 0.61, and 0.36, respectively; p = 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p = 0.036) in multivariate logistic regression. Conclusions: More physically active COPD patients show better functional status in terms of DLCO, PEmax, 6MWD, V̇O2peak, and systemic inflammation. Copyright © 2009 American College of Chest Physicians., This research was supported by Fondo de Investigación Sanitaria (FIS PI052292) and Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2004/136). Judith Garcia-Aymerich has a researcher contract from the Instituto de Salud Carlos III (CP05/00118), Ministry of Health, Spain. Jordi de Batlle had a predoctoral fellowship from the Instituto de Salud Carlos III (FI05/01022), Ministry of Health, Spain. Diego A. Rodríguez has a long term research fellowship from the European Respiratory Society (2006/191). The PAC-COPD Study is funded by grants from Fondo de Investigación Sanitaria (FIS PI020541), Ministry of Health, Spain; Agència d’Avaluació de Tecnologia i Recerca Mèdiques (AATRM 035/20/02), Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2002/137); Catalan Foundation of Pneumology (FUCAP 2003 Beca Maria Rava); Red RESPIRA (RTIC C03/11); Red RCESP (RTIC C03/09), Fondo de Investigación Sanitaria (PI052486); Fondo de Investigación Sanitaria (PI052302); Fundació La Marató de TV3 (No. 041110); DURSI (2005SGR00392); and an unrestricted educational grant from Novartis Farmacèutica, Spain. Centro de Investigacíon Biomedica en Red Epidemiologia y Salud Pública (CIBERESP) and CIBERES are funded by the Instituto de Salud Carlos III, Ministry of Health, Spain.

A functional definition of chronic obstructive pulmonary disease (COPD) based on airflow limitation has largely dominated the field. However, a view has emerged that COPD involves a complex array of cellular, organic, functional, and clinical events, with a growing interest in disentangling the phenotypic heterogeneity of COPD. The present review is based on the opinion of the authors, who have extensive research experience in several aspects of COPD. The starting assumption of the review is that current knowledge on the pathophysiology and clinical features of COPD allows us to classify phenotypic information in terms of the following dimensions: respiratory symptoms and health status, acute exacerbations, lung function, structural changes, local and systemic inflammation, and systemic effects. Twenty-six phenotypic traits were identified and assigned to one of the 6 dimensions. For each dimension, a summary is provided of the best evidence on the relationships among phenotypic traits, in particular among those corresponding to different dimensions, and on the relationship between these traits and relevant events in the natural history of COPD. The information has been organized graphically into a phenotypic matrix where each cell representing a pair of phenotypic traits is linked to relevant references. The information provided has the potential to increase our understanding of the heterogeneity of COPD phenotypes and help us plan future studies on aspects that are as yet unexplored.

To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV).Retrospective study in a tertiary care referral center.HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B).In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002).Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43·3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3·77, 95% CI 1·17–12·12), in patients with poor compliance with inhalation therapy (OR 3·25, 95% CI 1·18–8·93) and with severe lung function impairment (FEV1 OR 0·96, 95% CI 0·93-1·00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6·06, 95% CI 1·29–28·44) and influenza vaccination appeared to have a protective effect against this infection (OR 0·15, 95% CI 0·03–0·67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza.

Ten Spanish patients from six unrelated families diagnosed with desmin-related myopathy (DRM) were studied. The pattern of DRM inheritance was autosomal dominant in three families, autosomal recessive in one, and there was no family history in two cases. The disease onset was in early adulthood. Cardiac myopathy was the initial presentation in two patients, respiratory insufficiency in one, and lower limb weakness in all others. Cardiac involvement was observed in four patients. Lens opacities were found in four. CK level was normal or slightly elevated, and electrophysiological examination was consistent with myopathy. Muscle biopsies identified intracytoplasmic desmin-immunoreactive inclusions. In addition to desmin, synemin, actin, gelsolin, ubiquitin, αB-crystallin and amyloid βA4 were also present in the deposits. Ultrastructural examination revealed areas of myofibrillary disruption, abnormal electron-dense structures and accumulations of granulofilamentous material. A missense R406W mutation and a novel single amino acid deletion in the desmin gene were identified in two patients; the other patients did not show mutations in desmin, synemin, syncoilin or αB-crystallin genes. Analysis of 10 Spanish DRM cases illustrates a wide clinical, myopathological and genetic spectrum of DRM, reinforcing the need for further exploration of genetic causes for this group of disorders.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of admission to hospital among men in many countries, although the factors causing exacerbations are largely unknown. The association between readmission for a COPD exacerbation and a wide range of modifiable potential risk factors, after adjusting for sociodemographic and clinical factors, has been assessed. Methods: Three hundred and forty patients with COPD recruited during an admission for an exacerbation in four tertiary hospitals in the Barcelona area of Spain were followed for a mean period of 1.1 years. Information on potential risk factors, including clinical and functional status, medical care and prescriptions, medication adherence, lifestyle, health status, and social support, was collected at the recruitment admission. A Cox’s proportional hazards model was used to obtain independent relative risks of readmission for COPD. Results: During the follow up period 63% of patients were readmitted at least once, and 29% died. The final multivariate model showed the following risk (or protective) factors: ⩾3 admissions for COPD in the year before recruitment (hazard ratio (HR)=1.66, 95% CI 1.16 to 2.39), forced expiratory volume in 1 second (FEV 1 ) percentage predicted (0.97, 95% CI 0.96 to 0.99), oxygen tension (0.88, 95% CI 0.79 to 0.98), higher levels of usual physical activity (0.54, 95% CI 0.34 to 0.86), and taking anticholinergic drugs (1.81, 95% 1.11 to 2.94). Exposure to passive smoking was also related to an increased risk of readmission with COPD after adjustment for clinical factors (1.63, 95% CI 1.04 to 2.57) but did not remain in the final model. Conclusions: This is the first study to show a strong association between usual physical activity and reduced risk of readmission to hospital with COPD, which is potentially relevant for rehabilitation and other therapeutic strategies.

BACKGROUND--Tuberculous pleurisy is associated with small numbers of bacteria. Due to the low rate of primary resistance to antituberculous drugs a two-drug regimen was used to treat the condition. METHODS--Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months. Clinical, radiological, and haematological assessments were performed during treatment and patients were followed up for a median period of 41 (range 6-96) months. RESULTS--One hundred and thirty patients were studied with a mean age of 27 (range 11-53) years. Seven were withdrawn due to parenchymal disease and eight were lost to follow up during the treatment period. Side effects during treatment were frequent (20.7%), but only three patients required a change in medication. No treatment failures were observed. One hundred and fifteen patients completed therapy and were followed up for 41 (range 6-96) months with no evidence of a relapse. CONCLUSIONS--Tuberculous pleurisy responds well to a two-drug regimen of antituberculous therapy given for six months.