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Marc Miravitlles,1,2 Fernando González-Torralba,3 Cristina Represas-Represas,4 Xavier Pomares,2,5 Eduardo Márquez-Martín,2,6 Cruz González,7 Carlos Amado,8 Carles Forné,9,10 Soledad Alonso,11 Bernardino Alcázar,12 Miriam Barrecheguren,1 Juan María Jurado Mirete,13 Elsa Naval14 1Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), ISCIII, Madrid, Spain; 3Pneumology Department, Hospital Universitario del Tajo, Aranjuez, Spain; 4Pneumology Department, Hospital Álvaro Cunqueiro, Vigo, Spain; 5Pneumology Department, Corporació Sanità ria Parc Taulí, Sabadell, Spain; 6Medical-Surgical Unit for Respiratory Diseases, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 7Pneumology Department, Hospital Clínico de Valencia, Valencia, Spain; 8Pneumology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain; 9Heorfy Consulting, Lleida, Spain; 10Basic Medical Sciences Department, University of Lleida, Lleida, Spain; 11Pneumology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Spain; 12Pneumology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain; 13Scientific Department, GOC Health Consulting, Barcelona, Spain; 14Pneumology Department, Hospital Universitario de La Ribera, Alzira, SpainCorrespondence: Marc Miravitlles, Pneumology Department, Hospital Universitari Vall d’Hebron, P. Vall d’Hebron 119-129, Barcelona, 08035, Spain, Tel/Fax +34 932746083, Email marcm@separ.esIntroduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD.Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients’ characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal.Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician’s therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction.Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice.Keywords: COPD, exacerbation, bronchodilators, inhaled corticosteroids, eosinophils, withdrawal

Resumen A pesar de que es conocido que la presencia cronica de microorganismos en las vias aereas de pacientes con enfermedad pulmonar obstructiva cronica (EPOC) en fase de estabilidad conlleva una evolucion desfavorable, ninguna guia de manejo de la enfermedad establece pautas sobre como diagnosticar y tratar este tipo de casos. Con la intencion de orientar a los profesionales, desde la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) se ha elaborado un documento que pretende aportar respuestas clinicas sobre el manejo de pacientes con EPOC en los que se aislan microorganismos de forma puntual o persistente. Dado que la heterogeneidad de las evidencias cientificas disponibles no permite crear una Guia de Practica Clinica, se ha elaborado un documento basado en la literatura cientifica existente y/o en la propia experiencia clinica que aborda tanto la definicion de las diferentes situaciones clinicas como su diagnostico y manejo. El texto ha sido consensuado entre un amplio numero de neumologos con gran experiencia clinica y cientifica en este ambito. Este documento cuenta con el aval del Comite Cientifico de SEPAR.

Most of the published reviews about non-invasive home ventilation mainly reflect the technical aspects of ventilators. There is much less information about the consumables most used at home. However, the choice of a good interface or tubing system can lead to physiological changes in the patient–ventilator interaction that the clinician should be aware of. These physiological changes may affect the performance of the ventilator itself, the reliability of monitoring and, of course, the comfort of the patient. The use of different circuits, masks or filters is therefore related to the concepts of rebreathing, compressible volume, instrumental dead space or leak estimation and tidal volume. Through certain bench experiments, it is possible to determine the implications that each of these elements may have in clinical practice.

Introduction Long-term use of nebulized or oral antibiotics is common in the treatment of cystic fibrosis and non-cystic fibrosis bronchiectasis. To date, however, few studies have focused on the use of nebulized antibiotics in COPD patients. The aims of this study are: to establish whether a combination of nebulized colistin plus continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to Pseudomonas aeruginosa reduces the frequency of exacerbations, and to assess the effect of this treatment on microbiological sputum isolates. Material and methods A retrospective cohort was created for the analysis of patients with severe COPD and chronic bronchial infection due to P. aeruginosa treated with nebulized colistin at the Respiratory Day Care Unit between 2005 and 2015. The number and characteristics of COPD exacerbations (ECOPD) before and up to two years after the introduction of nebulized colistin treatment were recorded. Results We analyzed 32 severe COPD patients who received nebulized colistin for at least three months (median 17 months [IQR 7-24]). All patients but one received combination therapy with continuous cyclic azithromycin (median 24 months [IQR 11-30]). A significant reduction in the number of ECOPD from baseline of 38.3% at two years of follow-up was observed, with a clear decrease in P. aeruginosa ECOPD (from 59.5% to 24.6%) and a P. aeruginosa eradication rate of 28% over the two-year follow-up. Conclusion In patients with severe COPD and chronic bronchial infection due to P. aeruginosa, combination therapy with nebulized colistin and continuous cyclic azithromycin significantly reduced the number of ECOPD, with a marked decrease in P. aeruginosa sputum isolates.

Background: Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. Objective: Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. Methods: Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. Results: Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (p = 0.55) or hospitalizations (p = 0.07) with respect to the year prior to starting CC-A. Conclusions: Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

Aim: To characterize the respiratory virome in moderate/severe chronic obstructive pulmonary disease (COPD) patients using metagenomics, with healthy subjects as the reference. Patients & Methods: Sputum COPD samples were collected during stability and exacerbations with negative usual-care microbiologic analysis. Results: Eukaryotic viruses from the Anelloviridae, Herpesviridae and Retroviridae families and phages from the Shiphoviridae family were commonly found in COPD, and the respiratory virome in stability and noninfectious exacerbations showed a substantial similarity. DNA viruses with the highest relative abundance in COPD are Anelloviridae. Conclusion: These results support a colonizing role for eukaryotic viruses in COPD and highlight the importance of analyzing both DNA and RNA viruses when focusing on the respiratory virome.

Background Exacerbations of COPD (ECOPD) are a major cause of mortality and morbidity. Continuous cyclic azithromycin (CC-A) reduces the exacerbation rate, but it is unknown whether it remains effective and safe beyond the first year. Methods This study was a retrospective analysis of patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) with ≥ 4 moderate to severe ECOPD who received CC-A (500 mg three times per week) as add-on therapy. Patients treated over 24 months were considered long-term continuous cyclic azithromycin (LT-CC-A) users, and ECOPD, hospitalizations, and length of hospital stays during the first, second, and third years were compared with the previous 12 months. Microbiologic monitoring, assessment of macrolide resistance, and analysis of side effects were maintained throughout the study period. Results A total of 109 patients with severe COPD treated with CC-A (39 for ≥ 24 months) comprised the LT-CC-A group (35.8%). This group presented average reductions in ECOPD from baseline of 56.2% at 12 months, 70% at 24 months, and 41% at 36 months, paralleled by respective reductions in hospitalizations of 62.6%, 75.8%, and 39.8%. ECOPD due to common microorganisms fell by 12.5% and 17.3% at 12 and 24 months of LT-CC-A, respectively, with a 50% increase in macrolide resistance. Pseudomonas aeruginosa ECOPD rose by 7.2% and 13.1% at these two time points. CC-A therapy was well tolerated with few side effects: digestive disorders in the short term (7.1%) and hearing loss in the long term (5.1%). Conclusions LT-CC-A therapy over a 24- to 36-month period in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease grade D) achieved sustained reductions in ECOPD and hospitalizations of > 50% with few adverse events, although macrolide resistance increased.

Aims There are no specific criteria for a step-down or withdrawal dose of omalizumab (OMA). Our purpose was to evaluate the viability of a protocol for OMAlizumab DOse REduction (the OMADORE study) in severe allergic asthma (SAA). Methods The study population included 35 SAA patients treated during a minimum period of 1 year with oral corticosteroids (OC) equivalent to a mean daily dose of 4 mg of methyl-prednisolone. To qualify for the protocol, the patients had to have received treatment with OMA for at least one and a half years, OC dose had to have reached the lowest tolerated dose and spirometry had to be greater than or equal to that at entry. The interventions were (a) OMA dose was reduced by half; (b) if patients were clinically stable after 6 months, the dose was halved again; (c) if repeated OC boosters were needed and/or spirometry worsened by more than 10%, OMA dose was raised to the previous figure until stabilization. Results Mean age was 52.5 (17) years, median monthly OC dose was 120 (IQR: 225) mg. Pulmonary function: FVC: 79.7 (20.2)%; FEV1: 64.8 (21.7)%; FEV1/ FVC: 61.7(13.8)%. OMA could be withdrawn in 34.3% of the patients; 22.9% tolerated a reduction, and in 42.9% the dose could not be modified. Follow-up time after reduction or withdrawal ranged from 12 to 30 months. There were no severe exacerbations requiring emergency assistance or admission. Conclusions The OMADORE study found that in more than 50% of SAA patients on OC, OMA dose can be safely reduced or withdrawn based on a progressive dose reduction protocol.

Introduction The aim of this study was to assess several air-pressure settings for MI–E to determine their effect on peak cough flow (PCF), and to compare the best pressures with those are more common used in the literature (±40 cmH2O) in patients with neuromuscular disorders (NMD). Methods Adults with NMD in whom MI–E was indicated were recruited. Assisted PCF was measured by an external pneumotachograph. The protocol included 9 PCF measures per patient: 1 baseline (non-assisted), 4 with increasing inspiratory pressures without negative pressure (10, 20, 30 and 40 cmH2O or maximum tolerated), and then 4 adding expiratory pressures (−10, −20, −30 and −40 cmH2O or maximum tolerated) with maximum inspiratory pressure previously achieved. Results Twenty one patients were included, 61% with amyotrophic lateral sclerosis (ALS). Mean PCFs with recommended pressures (±40 cmH2O) were lower than the scored in the individualized steps of the titration protocol (197.7 ± 67 l/min vs 214.2 ± 60 l/min, p Conclusion The PCFmax obtained with the protocol did not always match the recommended settings. It may be advisable to perform MI–E titration assessed by non-invasive PCF monitoring in patients with NMD, especially in ALS with bulbar involvement to improve the therapy detecting airway collapse induced by high pressures.

Background Roflumilast is used in severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. However, limited information is available on its impact in a “real-life” population that may be receiving triple therapy. Objective This study aimed to evaluate the effectiveness and safety of roflumilast in COPD patients already receiving triple therapy (long-acting β -agonist/inhaled corticosteroids and long-acting muscarinic antagonist). Methods Prospective registry that included COPD patients who were prescribed roflumilast added to triple therapy. The yearly rate of all COPD exacerbations before and after roflumilast and side effects related to the drug were registered. Results Among 55 patients prescribed 500 mg of roflumilast. Only 50.9% ( n = 28) completed 1 year of therapy (roflumilast group). A reduction of all exacerbations with roflumilast was observed (2.75 ± 0.29 vs. 3.57 ± 0.26; P = 0.022), with a particular benefit in patients with ≥4 exacerbations prior to initiating therapy (3.55 ± 0.51 vs. 5.00 ± 0.30; P = 0.034). Side effects (mainly gastrointestinal) and treatment discontinuation occurred in 69.1% and 49.1% of the overall population, respectively. Conclusions Roflumilast, when added to triple therapy, reduces exacerbations in a “real-life” population of severe COPD patients with frequent exacerbations. However, side effects are more common and lead more frequently to discontinuation of therapy than has been reported in trials.

Background: We aimed to determine the mortality two months after exacerbation of chronic obstructive pulmonary disease (eCOPD) and to identify factors associated with mortality, comparing patients admitted to wards and those discharged to home from the emergency department. Methods: This prospective multicentre study included all consecutive patients presenting with eCOPD at emergency departments in 16 public hospitals in Spain. Clinical variables were recorded from a standardized questionnaire . Independent predictors of mortality were modelled by logistic regression analysis. The calibration and discriminative power of the models for the two groups (discharged and admitted) were estimated by the Hosmer-Lemeshow test and the area under the curve (AUC), respectively. Bootstrap methods were applied for internal validation. Results: 2487 patients were included; 1537 (62%) of these were admitted to wards. A total of 155 (6.2%; 95% CI: 5.2% - 7.1%) patients had died at 2 months: mortality was four times higher in patients admitted than in patients discharged. Age ≥ 80 years, Charlson score >2, and pronounced dyspnoea were independent factors for mortality in both groups; in admitted patients, Glasgow scale, baseline treatments for COPD, previous heart disease, complications during hospitalization, and corticoids at discharge were also independent factors.

Background: Mechanical assistance cough for patients with neuromuscular disorders (NMD) is commonly used, but there is no adaptation model established. Currently is performed subjectively by the physiotherapist following the pressures recommended in the current literature (LRP) as optimal (±40CmH 2 O). Aim: To check if LRP are the most optimal pressures to achieve the better peak cough flow (PCF). Method: Repeated measures study was performed to evaluate the effectiveness measured by PCF. Subjects adults with cough assist (CA) criteria (PCFbaseline 2 O (10 to 40cmH 2 O) and 4 adding expiratory pressures (±10 to ±40cmH 2 O). Results: Eighteen patients were included, 67% of them were diagnosed of Amyotrophic Lateral Sclerosis (ALS). High pressures (> ±35cmH 2 O) were the most optimal to achieve the best PCF by 50% of patients, 78% of them were ALS. The rest were achieved with low pressures ( 2 O), 55% of them were ALS. Statistically significant differences were found in the comparison between PCFbaseline and PCFmaximum (max) (p Conclusion: PCFmax obtained did not match always with the PCFL, for this, is advisable to perform CA adaptation individualized by monitoring in patients with NMD to improve the therapy.

[EN] Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone (MP) was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO) measurement were performed and the accumulated monthly MP dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of MP, FeNO and blood immunoglobuline E (IgE) values, or spirometry (perennial: FVC: 76%; FEV1: 62%; seasonal: FVC: 79%; FEV1: 70%). The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and MP consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity.

INTRODUCTION: The effect of leaks on volume-targeted pressure support noninvasive ventilation mode has only been tested with continuous simulated leaks. The objective of the study was to assess the influence of random leaks occurring either during inspiration or expiration. METHODS: Analysis of the volume-targeted pressure support mode in 6 commercial ventilators with single-limb circuits and intentional leak in a bench study (restrictive model). Unintentional leaks were introduced through a mechanical system during inspiration (threshold valve with 2 levels of leaks) or during expiration (active valve). Results of delivered tidal volume (VT) and pressure support were externally recorded. A pre-set VT of 550 mL was programmed, with a wide range of pressure support values. RESULTS: All the ventilators showed a deviation of delivered versus programmed VT below 10% in the period without unintentional leaks. In the model with unintentional inspiratory leaks, a progressive drop in delivered VT and pressure support was observed for all ventilators. The reduction in the delivered VT for the highest inspiratory leak ranged between 21 and 40%, corresponding to a decrease in pressure support between 3.09 and 10.15 cm H2O after 5 min. Conversely, in the expiratory model, increases in delivered VT and pressure support were observed, ranging between 16 and 33% and between 2.7 and 6.5 cm H2O, respectively. CONCLUSIONS: The introduction of random leaks influences the performance of commercial ventilators with single-limb circuits and intentional leak. The decrease in delivered VT with inspiratory leaks reaches a magnitude that may have clinically important impacts.

Altres ajuts: This work was supported by Fundació Catalana de Neumología (FUCAP) and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias(CIBERES). CIBERES is an initiative of the Instituto de Salud Carlos III. The bronchial microbiome in chronic lung diseases presents an abnormal pattern, but its microbial composition and regional differences in severe asthma have not been sufficiently addressed. The aim of the study was to describe the bacterial community in bronchial mucosa and secretions of patients with severe chronic asthma chronically treated with corticosteroids in addition to usual care according to Global Initiative for Asthma. Bacterial community composition was obtained by 16S rRNA gene amplification and sequencing, and functional capabilities through PICRUSt. Thirteen patients with severe asthma were included and provided 11 bronchial biopsies (BB) and 12 bronchial aspirates (BA) suitable for sequence analyses. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria showed relative abundances (RAs) over 5% in BB, a cutoff that was reached by Streptococcus and Prevotella at genus level. Legionella genus attained a median RA of 2.7 (interquartile range 1.1-4.7) in BB samples. In BA a higher RA of Fusobacteria was found, when compared with BB [8.7 (5.9-11.4) vs 4.2 (0.8-7.5), p = 0.037], while the RA of Proteobacteria was lower in BA [4.3 (3.7-6.5) vs 17.1 (11.2-33.4), p = 0.005]. RA of the Legionella genus was also significantly lower in BA [0.004 (0.001-0.02) vs. 2.7 (1.1-4.7), p = 0.005]. Beta-diversity analysis confirmed the differences between the microbial communities in BA and BB (R 2 = 0.20, p = 0.001, Adonis test), and functional analysis revealed also statistically significant differences between both types of sample on Metabolism, Cellular processes, Human diseases, Organismal systems and Genetic information processing pathways. The microbiota in the bronchial mucosa of severe asthma has a specific pattern that is not accurately represented in bronchial secretions, which must be considered a different niche of bacteria growth. The online version of this article (doi:10.1186/s12866-017-0933-6) contains supplementary material, which is available to authorized users.

The respiratory Day Hospital (DH) is a care facility currently operating at various healthcare institutions. It monitors patients with severe chronic obstructive pulmonary disease (COPD) presenting repeated exacerbations with at least two hospital admissions per year. The main aim of the study was to evaluate the effectiveness of the DH program for controlling admissions for COPD exacerbations in this cohort of patients, and to identify clinical factors associated with hospitalizations and mortality. An observational prospective multicenter study was carried out at three hospitals. The sample comprised 150 consecutive patients (median age 70 [65-76] years, FEV1 33 [26-43]%, 97% males), included at the DH program. Over a one-year period, variables assessing effectiveness and use of healthcare resources were recorded. Factors associated with hospitalizations and mortality were identified. Patients made a median of 4[2-5] emergency visits due to COPD exacerbations with a median of 1[0-2] hospitalization(s)/year. Most of exacerbations (77%) were evaluated at the DH, but there were fewer hospitalizations from the DH than from the emergency department (21% vs. 81%, p < 0.001). In all, 29% of the patients had at least two admissions; these were the patients with the most severe disease. Age, readmission at 30-days and the presence of respiratory failure were the predictors of mortality. In conclusion, the DH program is an effective model for reducing hospitalizations in this cohort of patients. In all, 29% of the patients required two hospital admissions or more; these patients had more advanced disease and poorer prognosis, and would be most likely to benefit from additional care support.

Resumen Fundamento y objetivo Las exacerbaciones de la enfermedad pulmonar obstructiva cronica (EA-EPOC) constituyen un factor determinante en el deterioro de los pacientes, con gran repercusion sobre el gasto sanitario. El objetivo de este estudio fue evaluar el impacto de la atencion de las EA-EPOC en un hospital de dia de enfermedades respiratorias (HDER) sobre la tasa de ingresos hospitalarios. Pacientes y metodo Durante 14 meses se recogieron prospectivamente todos los episodios de EA-EPOC atendidos en el HDER y en el Servicio de Urgencias, excluyendo a los pacientes con otra causa de agudizacion o necesidad de ventilacion mecanica invasiva. Resultados Se incluyeron 226 episodios (173 pacientes, edad media [DE] de 72 [8] anos). En el HDER se atendieron 121 (53,5%). El numero de ingresos en el grupo del HDER fue claramente inferior (32,2 frente a 66,7%, p Conclusiones El manejo de las EA-EPOC en el HDER parece reducir el numero de ingresos hospitalarios en comparacion con un Servicio de Urgencias.

Fundamento y objetivo Evaluar la relacion entre el cuestionario Chronic Obstructive Pulmonary Disease Assessment Test (CAT) y la gravedad de la enfermedad pulmonar obstructiva cronica (EPOC) valorada segun el indice multidimensional BODE, en pacientes con obstruccion grave al flujo aereo (forced expiratory volume in one second [FEV1, «volumen espiratorio forzado en el primer segundo»] posbroncodilatador < 50%) en fase estable. Material y metodo Estudio prospectivo observacional (2012). Se clasifico la gravedad de la EPOC segun el indice BODE en 3 subgrupos: EPOC leve-moderada (BODE < 5 puntos), EPOC grave (BODE 5-6 puntos) y EPOC muy grave (BODE = 7 puntos). Resultados Se incluyeron 97 pacientes con una edad media (DE) de 67 (8) anos, el 96% eran varones. El FEV1 medio fue del 34,3% (9,8%) y el indice BODE medio fue de 4,8 (1,4). La puntuacion media del CAT fue de 20 (7,7). No observamos diferencias significativas en la puntuacion del CAT (total o por items) en funcion de los 3 grupos de BODE evaluados. Conclusiones En pacientes con EPOC y obstruccion grave al flujo aereo, la puntuacion en el CAT refleja un impacto de la enfermedad moderado-grave y no permite predecir la gravedad de la EPOC evaluada segun el indice BODE.

Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug's tolerance and oral corticosteroid sparing capacity in a long-term observational study.Thirty-two patients aged ≥18 years with obstructive airway disease and FEV(1) reversibility ≥12% and 200 mL, with an oral steroid requirement ≥7.5 mg per day of prednisolone during a period of ≥1 year, a positive prick test or in vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline immunoglobulin E level ranking between 30-700 IU/mL were prospectively followed for 17.2 ± 8.5 months. Patients were visited once or twice a month, depending on their schedule for omalizumab administration.blood analysis every six months; spirometry and nitric oxide measurement at every visit.One patient who dropped out early was excluded. Follow-up period: the treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were reduced from 7.19 ± 11.1 to 3.29 ± 11.03 mg (p 0.002) and withdrawn in 74.2% of patients. FEV(1) (percent predicted) was 64.4 ± 22.7 at the beginning and 62.9 ± 24.3 at the end. IgE at entry was 322.2 ± 334.2 IU/mL and increased 2.34-fold. Respiratory function and NO did not present statistically significant changes. We identified three groups of patients: the first (n = 17) receiving oral steroid at entry in whom the accumulated dose of oral steroids progressively decreased; another (n = 10) including patients who had quit oral steroids before starting omalizumab although they had not been instructed to do so and whose oral steroid dose at the end of follow-up was zero; and a third group (n = 4) that did not benefit from omalizumab treatment. The only relevant side effect was a flu-like syndrome which required discontinuation of treatment in one patient.In our series, a substantial, safe decrease in oral corticosteroid requirements was observed due, at least to some extent, to omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the patients. We were unable to identify a factor able to predict which patients would benefit most from omalizumab treatment.

Resumen Objetivo El objetivo del estudio es evaluar las causas de muerte y factores pronosticos de mortalidad en una cohorte de pacientes con enfermedad pulmonar obstructiva cronica (EPOC) grave. Pacientes y metodos Se incluyo a 203 pacientes con EPOC grave (volumen espiratorio forzado en el primer segundo Resultados La edad media (±desviacion estandar) de los pacientes fue de 69±8 anos, y el volumen espiratorio forzado en el primer segundo del 30,8±8,2%. Fallecieron 109 pacientes (53,7%). De estos, 72 murieron de causas respiratorias (80,9%), de las cuales la exacerbacion de la EPOC fue la mas frecuente (48,3%). Durante el seguimiento, el 18,7% preciso ingreso en la Unidad de Cuidados Intensivos (UCI). La supervivencia al ano, a los 3 y 5 anos fue del 80, el 53 y el 26%, respectivamente. El analisis multivariante mostro que la mortalidad se asociaba a la edad, al estadio IV de la clasificacion de la Global Initiative for Chronic Obstructive Lung Disease (GOLD), al cor pulmonale y a la estancia hospitalaria durante el ano previo a la inclusion. La necesidad de ingreso en la UCI durante el seguimiento constituyo un factor independiente asociado a mayor mortalidad. Conclusiones La mortalidad en la EPOC grave es elevada y la exacerbacion de la enfermedad constituye la causa mas frecuente. La edad, el estadio GOLD, el cor pulmonale, los ingresos hospitalarios previos y la necesidad de ingreso en la UCI durante el seguimiento son factores pronosticos independientes de mortalidad.

The monitoring of home noninvasive ventilation by built-in software should accurately reflect the amount of gas entering into the patient’s airways. For this purpose, the native curves should be transformed through mathematical algorithms designed for and adapted to the configuration of different tubing, the expiratory system, and the physical phenomena that can occur in clinical practice.

We present chest radiograph, CT and MRI findings in a case of pulmonary hematoma associated with anticoagulant therapy. The lesion presents as a well-defined mass in the right lower lobe; shows high density on unenhanced CT. At MRI performed 50 days after the first consultation, the nodule is hyperintense in T2-weighted MRI images and hypointense with a hyperintense peripheral rim in T1-weighted images.

Summary Objective To compare the effectiveness and efficiency of an initiation protocol for non-invasive home mechanical ventilation (NIHMV) carried out at a pulmonary outpatient clinic with the standard in-hospital model. Methods Prospective, observational study. Population: 16 patients divided into two groups: (A) outpatient protocol \( n = 9 \) ; and (B) standard in-hospital initiation with an elective admission \( n = 7 \) . Instrumentation: at baseline condition and treatment starting, arterial blood gases and nocturnal pulse-oximetry were performed. At the end of follow-up, arterial blood gases and patient compliance (ventilator's built-in counter) was determined. Efficiency was evaluated by calculating cost savings per ventilated patient for the financier and accumulated days of hospitalization saved. Results No differences in baseline conditions were observed. Ventilation was effective in the two groups: a significant decrease in PaCO 2 and an increase in mean nocturnal oxygen saturation were observed after initiating ventilation. (Group A: PaCO 2 :42.9±1.5; SpO 2 :91.9±1.9; Group B:PaCO 2 :44.3±6; SpO 2 :91.9±2.7). At three months the effectiveness of ventilation and the number of hours of ventilation was equivalent in all groups. The new model cut costs for the health care financier by 50%. The outpatient sessions saved 63 days of hospitalization. Conclusions (1) Outpatient initiation is an effective and efficient alternative to the traditional in-hospital method for NIHMV. (2) The outpatient protocol represents a substantial saving for the financier.

Background: Omalizumab (OMA) is marketed for severe asthma patients allergic to perennial allergens. Our purpose was to investigate whether OMA is also as effective in severe asthma due to seasonal allergens. Method: Population: 30 patients with oral corticosteroid-dependent asthma (receiving 4 mg of methyl-prednisolone (MP) per day ≥ 1 year or boosters of MP equivalent to a mean daily dose of 4 mg of MP). For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. Protocol: a) OMA dose was calculated according to the dosing table; b) patients were considered responders or non-responders after six months of treatment with OMA; c) the dose of oral MP was tapered at a rate of 2 mg every two weeks depending on tolerance; f) at every monthly visit, forced spirometry (S) was performed and the accumulated monthly MP dose was calculated. Results: At entry there were no differences in gender, body mass index or obesity, monthly dose of MP or S between groups (Perennial: FVC: 76% (20); FEV1: 62% (22); Seasonal: FVC: 79% (12); FEV1:70% (16)). Follow-up: One patient in each group was considered a non-responder; S did not deteriorate in either group. There was a significant intragroup decrease in MP consumption (p

Background: Bronchial microbiome has not been studied in severe persistent asthma and its characterization in bronchial mucosa and aspirates is needed Objective: To characterize the bronchial microbiome of oral corticosteroid-dependent asthma patients Methods: bronchial biopsies (BB) and aspirates (BA) were obtained through bronchoscopy; 16S rRNA gene was sequenced and bacterial relative abundances (RA), richness and evenness were compared Results: 13 patients with a mean age of 49 years (SD 14) and a FEV 1 of 72% (55.7-88.5) were included; 11 BB and 12 BA samples were analyzed. Firmicutes, Proteobacteria and Bacteroidetes were the predominant phyla, with Prevotella and Streptococcus as the genera with higher RA in both samples. Bacteroidetes and Fusobacteria phyla showed significantly higher RA in BB than in BA samples [33 (21-35) vs 22 (14-28) p=0.044 and 6.5 (4-11) vs 2 (0.7-5.5) p=0.006, respectively]. 109 out of 364 identified genera showed significant differences between the samples, with higher RA for 73 in BB and 36 in BA samples. Chao 1 richness parameter was higher in BA samples [3038(2422-4564) vs 1741(1318-2072), p vs 6.7 (6-7), p=0.032], confirming that BA community is dominated by some taxa. Bray-Curtis β-diversity parameter and adonis test confirmed that the community structure in BB and BA samples was significantly different (p Conclusions: In severe corticosteroid-dependent asthma, 1) the microbiota of the bronchial mucosa is composed mainly by Firmicutes, Proteobacteria and Bacteroidetes phyla; 2) The BA microbiota is not representative of the bronchial mucosa microbiome Funded by FUCAP, SEPAR and ISCIII.

Background: The course of COPD is frequently aggravated by exacerbations. New molecular techniques have suggested that many bacterial groups, not only the common COPD pathogens, could trigger the exacerbations. Objective: to analyze the microbial community and the gene content of samples obtained during stability and exacerbation of COPD patients. Method: 16S rRNA was pyrosequenced to obtain the taxonomic information. The metabolic information was obtained with the Metagenomics RAST server (MG-RAST) with KEGG database. Results: 8 severe COPD patients were included. At genus level, 68 different OTUs were found. No significant differences in the relative abundance of any of the detected genera were found between stability and exacerbation. Bacterial biodiversity, measured with Chao1 and Shannon indexes, showed no significant differences either. Beta-diversity analysis with Bray-Curtis index showed that the microbial composition was similar in both clinical situations (Adonis test R2= 0.02 p= 0.955). In the MG-RAST analysis, at KEGG level 2, 36 functional categories were found, 4 of them with significant differences.Cell growth and dead and Transport and catabolism decreased their abundance in exacerbation [1.6 (0.2-2) vs 4 (3-7) p=0.012 and 2 (0-3) vs 4 (2-5) p= 0.025] while Cancer and Carbohydrate metabolism were more abundant in exacerbation [0.8 (0-1.5) vs 0 (0-0.5) p= 0.043 and 7 (6-9) vs 6 (6.3-6.1) p= 0.012]. Conclusion: The microbiome composition did not show differences between stability and exacerbation samples. However, during an exacerbation, increases and decreases in some functional pathways are observed, suggesting that exacerbations are associated with an alteration in the functional activity of the bacterial community.

Resumen La telangiectasia hemorragica hereditaria (THH) es una enfermedad autosomica dominante caracterizada por la triada de epistaxis, telangiectasias y malformaciones vasculares. Las complicaciones vasculares pulmonares asociadas a esta enfermedad incluyen malformaciones arteriovenosas (MAV) pulmonares y, de forma menos frecuente, hipertension pulmonar (HP). El presente caso clinico hace referencia a un paciente con multiples MAV pulmonares e HP en el contexto de posible THH. Se procedio a embolizacion de una MAV y se inicio tratamiento especifico de hipertension arterial pulmonar con un antagonista de receptores de endotelina. A continuacion se describe su mejoria funcional y hemodinamica tras 3 anos de seguimiento.

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 [FEV 1 %] 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 FEV 1 % values were over the median and as advanced when FEV 1 % 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.

Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis.

To evaluate the relationship between Chronic Obstructive Pulmonary Disease Assessment Test (CAT questionnaire) and chronic obstructive pulmonary disease (COPD) severity assessed by the multidimensional BODE index in patients with severe airflow obstruction (forced expiratory volume in one second [FEV1] post-bronchodilator50%) in a stable state.Prospective observational study (2012). We classified the severity of COPD according to the BODE index in 3 subgroups: mild to moderate COPD (BODE5 points), severe COPD (BODE 5-6 points) and very severe COPD (BODE ≥ 7 points).We included 97 patients with a mean age of 67 (8) years, 96% were men. The mean FEV1 was 34.3% (9.8%) and mean BODE index was 4.8 (1.4). The mean CAT score was 20 (7.7). We found no significant differences in CAT score (total or by items) between the 3 groups of BODE assessed.In patients with COPD and severe airflow obstruction, the CAT score reflects a moderate to severe impact of illness and does not allow to predict COPD severity assessed by the BODE index.

Omalizumab is an effective drug for allergic asthma. The purpose of this study was to evaluate the effectiveness and tolerance of this drug in non-allergic GINA step V asthma patients. This study was single-centre, prospective, open-label, observational, naturalistic. Non-allergic asthma patients requiring a mean dose of oral prednisolone of at least 5 mg/day during greater than or equal to 1 year or an accumulated oral corticosteroid dose/year greater than or equal to 1500 mg were enrolled. At entry and the end of the 12-month follow-up we measured blood eosinophilia and IgE concentration; at every monthly visit a forced spirometry and exhaled fraction of nitric oxide (NO) were carried out. The subjects were seven adult patients (5 female), age range 37-63 years, with the following mean values: IgE: 226.7+/-176 IU/mL; FVC 74+/-18 percent; FEV1 57+/-11 percent; NO: 21.2+/-7 ppb. The study was approved by the IRB of the hospital. One patient decided to stop treatment after 12 weeks and was excluded from the evaluation. We did not observe changes in eosinophil count, spirometry or NO values. Three patients considered responders did not need prednisolone during the follow-up. The mean daily dose of prednisolone fell from 6.6+/-8.1 mg/day at entry to 1.5+/-2.3 mg/day (p less than 0.16) at the end of follow-up. The mean monthly accumulated dose fell from 92+/-112 to 12+/-26 mg/month (p=0.26). Total blood IgE increased 1.93-fold. Side effects were only local: treatment tolerance was excellent; three out of six patients seemed to slightly benefit from anti-IgE treatment; to date there is no evidence strong enough to systematically prescribe omalizumab in non-allergic asthma patients.

New home ventilators are able to provide clinicians data of interest through built-in software. Monitoring of tidal volume (VT) is a key point in the assessment of the efficacy of home mechanical ventilation.To assess the reliability of the VT provided by 5 ventilators in a bench test.Five commercial ventilators from 4 different manufacturers were tested in pressure support mode with the help of a breathing simulator under different conditions of mechanical respiratory pattern, inflation pressure, and intentional leakage. Values provided by the built-in software of each ventilator were compared breath to breath with the VT monitored through an external pneumotachograph. Ten breaths for each condition were compared for every tested situation.All tested ventilators underestimated VT (ranges of -21.7 mL to -83.5 mL, which corresponded to -3.6% to -14.7% of the externally measured VT). A direct relationship between leak and underestimation was found in 4 ventilators, with higher underestimations of the VT when the leakage increased, ranging between -2.27% and -5.42% for each 10 L/min increase in the leakage. A ventilator that included an algorithm that computes the pressure loss through the tube as a function of the flow exiting the ventilator had the minimal effect of leaks on the estimation of VT (0.3%). In 3 ventilators the underestimation was also influenced by mechanical pattern (lower underestimation with restrictive, and higher with obstructive).The inclusion of algorithms that calculate the pressure loss as a function of the flow exiting the ventilator in commercial models may increase the reliability of VT estimation.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the triad of epistaxis, telangiectasia and vascular malformations. Pulmonary vascular complications associated with this disease include pulmonary arteriovenous malformations (AVM) and, less frequently, pulmonary hypertension (PH). We report the case of a patient who presented multiple pulmonary AVM and PH probably due to HHT. Embolization was carried out on one of the AVM and the patient received specific pulmonary arterial hypertension treatment with an endothelin receptor antagonist. We also described the patient's functional and hemodynamic improvement after almost 3 years of follow-up.

Aim: To identify microorganisms unrecognized through culture in the lower airway of patients with chronic pulmonary disease through amplification and pyrosequencing of specific genes for microbial diversity assessment Method: To avoid culture-related bias, 1) DNA extraction from respiratory samples (sputum, bronchial aspirate (BAS), bronchoalveolar lavage (BAL) and bronchial mucosa); 2) 16S rRNA amplification and purification with modified primers which include a specific 8 nucleotides code per sample; 3) Pyrosequencing of amplified products by Titanium/GS-FLX System (454-Roche; 4) Obtention of >500 sequences per sample; and 6) Comparison of the results obtained with the diferent samples using bronchial mucosa as gold standard. Results: Sputum, BAS, BAL and bronchial mucosa samples from 6 patients were studied. Over 500 sequences of gen 16S were identified in 17 out of 24 samples. Total number of bacterial genera per patient were over 100. Analysis of coincidence obtained from bronchial mucosa showed low coincidence with BAS and sputum, and maximal coincidence with BAL, that showed a range of 55-74 bacterial genera. Streptococcus, Prevotella, Moraxella, Haemophilus, Acinetobacter, Fusobacterium and Neisseria were the most often identified genders, accounting for up to 60% of the overall. Conclusions: Pyrosequencing is applicable to samples of bronchial secretions and is able to demonstrate a microbial diversity over 600 microorganisms. Sputum and BAS samples were non-representative of bronchial mucosa, but BAL that mostrates over fifty bacterial genera, shows the closest results with bronchial mucosa. Sponsorship by Fundacio Parc Tauli.

CIBERES, Ciber de enfermedades respiratorias, Spain Home-based noninvasive ventilation (NIV) was initiated in the early nineties in our environment as a treatment for patients with chronic respiratory failure, secondary to restrictive ventilatory disorders or neuromuscular disease. Subsequently, NIV also proved effective in patients with obesity-related hypoventilation syndromes, and to a lesser extent in some patients with chronic obstructive pulmonary disease in stable phase. There was a simultaneous growth in interest in whether the selected parameters suited the patients’ needs when using NIV in the home setting. Thus, the use of continuous overnight pulse oximetry monitoring as the gold standard for home monitoring in centers prescribing ventilation became widespread. The main issue with pulse oximetry has undoubtedly been its lack of specificity for correlation with certain patterns of patient–ventilator interaction. In other words, the effects of adverse events (desaturation) were detected, but there was a limited understanding of the underlying causes, and therefore of the potential solutions. In order to improve the performance of pulse oximetry, a series of simplified polygraphic systems have appeared in recent years, mostly in association with the ventilator manufacturers. These systems provide a set of data on the patient’s respiratory mechanics that can be downloaded from the ventilator’s internal memory. The main purpose is to provide the clinician with additional information on the potential reasons for inadequate ventilation periods and the pathophysiological causes (unintentional interface leaks, uncorrected upper airway episodes, asynchrony, etc.). Over the years, almost all manufacturers of ventilation systems have developed their own download system and data display. 1 However, in our view, the performance and reliability of these devices, which are widely used today, should be analyzed in depth. The first premise to be considered by the clinician is that a number of values provided by these software systems are not measured directly. In single-tube systems, the most widely used in home

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are considered to be the most important factor in determining the course of the disease, and have great impact on the health care system. We evaluated the effects of a Respiratory Day Hospital (RDH) on the rate of hospital admissions due to AE-COPD.During 14 months, every case of AE-COPD seen at the RDH and emergency services was recruited prospectively. Patients were excluded when another known cause of exacerbation was present and/or when they required invasive mechanical ventilation.226 episodes (173 patients) were included (72, SD 8 years old). One hundred and twenty one cases received treatment at the RDH (53.5%). Admissions from the RDH group were noticeably lower (32.2 vs. 66.7%, p0.001), even in patients with more admissions due to AE-COPD the year before the study. There were no differences either in terms of AE-COPD severity or in readmissions and mortality rates during the follow up.Management of AE-COPD in a RDH seems to be associated with a lower rate of hospital admissions in comparison with an emergency department.