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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.

Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain 'omics' (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

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.

BackgroundThe respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.MethodsCross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing. The microbiome composition was analysed with QIIME.ResultsWe observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with 2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p=0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels 2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p=0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p=0.020], and a significant increase in the RAs of 20 genera.ConclusionThe respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels., This study was funded by FIS PI15/00167 and PI15/02042 from Instituto de Salud Carlos III (ISCIII), SAF 2014-54371 (FEDER) from Ministerio de Economia y Competitividad, Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Laboratorios Menarini S. A, Fundacio Pla Armengol and Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES). CIBERES is an initiative of the ISCIII.; This work was also supported by grants from Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya (2017 GRC-716).

[ES] La enfermedad pulmonar obstructiva crónica (EPOC) es una entidad de presentación heterogénea. Por ello, se han intentado perfilar diferentes fenotipos y endotipos, que permitirían un manejo más diferenciado. El objetivo del proyecto Biomarcadores en la EPOC (BIOMEPOC) es identificar biomarcadores sanguíneos útiles para tipificar mejor a los enfermos. Se analizarán datos clínicos y muestras sanguíneas en un grupo de pacientes y controles sanos. El proyecto constará de fases de prospección y de validación. Se realizarán determinaciones analíticas sanguíneas con técnicas convencionales y de diversas ciencias «ómicas» (transcriptómica, proteómica y metabolómica). Las primeras se realizarán orientadas por hipótesis, mientras que con las segundas se realizará una exploración sin dicho condicionante. Finalmente se realizará un análisis multinivel. En el momento actual se han reclutado 269 pacientes y 83 controles, y se está iniciando el procesamiento de muestras. Con los resultados obtenidos se espera identificar nuevos biomarcadores que, en solitario o combinados, permitan una mejor tipificación de los pacientes., [EN] Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain ‘omics’ (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

Objective: To evaluate the relationships between respiratory microbiome and main COPD phenotyes Methods: Sputum samples from COPD patients were obtained during stability and 16S rRNA gene was analyzed. Taxonomic and diversity information were correlated with frequent exacerbator (FE) and eosinophilic COPD (EC) phenotypes Results: 78 subjects were analyzed, mean age 67 (SD 9) years. Patients with ≥2 exacerbations the previous year were considered FE (n=23). Their bacterial community was significantly different (p=0.014) from patients with no exacerbations (n=31), with changes in RA of 3 phyla and 13 genera, which included an increase in Pseudomonas. Patients with 1 exacerbation (n=18) showed borderline differences in their bacterial community (p=0.081) compared to no exacerbations patients, with a loss of RA of 2 phyla and 13 genera. Patients with 1 or ≥2 exacerbations showed similar borderline differences (p=0.087) with changes in RA of 4 genera. EC patients, identified by a systemic eosinophil level ≥2%, showed a significantly more diverse respiratory microbiome [Chao1 224.5 (74.9) vs 280.5 (79.6) p=0.003; Shannon 3.9 (1.1) vs 4.6 (1.1) p= 0.010] and a different community structure (p=0.037), mediated by a significant increment of 4 phyla and 26 genera Conclusion: A specific bacterial composition was shown in stability samples of FE and EC phenotypes. The presence of 1 exacerbation the previous year produces significant changes in the RA of specific OTUs and in patients with ≥2 exacerbations these changes lead to significant differences in their bacterial community. The respiratory microbiome was more diverse in EC patients and with a specific bacterial community Funded by FIS 15/00167, SEPAR and BRN-Pla Armengol

Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain 'omics' (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationship between methylation status of p16, DAPK, RASSF1a, APC and CDH13 genes in lymph nodes sampled by EBUS-NA, tumor staging and prognosis. Methylation status of DAPK, p16, RASSF1a, APC and CDH13 genes was assessed in EBUS-NA cell blocks from LC patients and related to stage and survival. Eighty-five consecutive patients [mean age 67 (SD 8)] were included. Methylation of ≥1 gene was found in 43 malignant nodes (67 %). A higher prevalence of RASSF1a methylation was observed in small cell lung cancer patients [9/10 (90 %) vs. 15/53 (28 %); p < 0.001 χ(2) test]. Methylation of APC and/or p16 was related to advanced staging in non-small cell lung cancer (NSCLC) [15/29 (52 %) vs. 6/24 (25 %), p = 0.048, χ(2) test]. Patients with NSCLC showing methylation of APC and/or p16 had also lower 6-month survival (p = 0.019, log rank test), which persisted after adjustment for age and subtyping (HR = 6, 95 % CI [1.8-19.5], p = 0.003, Cox regression). Epigenetic analyses are feasible in EBUS-NA cell blocks and may identify methylation patterns associated with worse prognosis. Methylation of p16 and APC genes in NSCLC patients was associated with advanced staging and lower 6-month survival.

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.

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.

Altres ajuts: Sociedad Española de Neumología y Cirugía Torácica 226/2012 Staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC) is mandatory. The maximum Standard Uptake Value (SUVmax) obtained using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive technique available for this evaluation, but its performance varies from center to center. The aim of the present study was to identify FDG-PET predictors of mediastinal malignancy that are able to minimize intercenter variability and improve the selection of subsequent staging procedures. A multicenter study of NSCLC patients staged through FDG-PET and endobronchial ultrasonography with needle aspiration (EBUS-NA) was performed using therapeutic surgery with systematic nodal dissection as gold standard. Intercenter variability and predictive power for mediastinal malignancy of different FDG-PET measures were assessed, as well as the role of these measures for selecting additional staging procedures. One hundred and twenty-one NSCLC patients, of whom 94 (72%) had ≥1 hypermetabolic spots in the mediastinum, were included in the study. Mean SUVmax of the primary tumor was 12.3 (SD 6.3), and median SUVmax of the highest hypermetabolic spots in the mediastinum was 3.9 (IQR 2.4-7). Variability of FDG-PET measures between hospitals was statistically significant (p = 0.016 and p < 0.001 respectively), but lost significance when SUVmax in the mediastinum was expressed as a ratio or a subtraction from the primary tumor (SUVmax mediastinum/tumor, p = 0.083; and SUVmax mediastinum - tumor, p = 0.428 respectively). SUVmax mediastinum/tumor showed higher accuracy in the ROC analysis (AUC 0.77 CI 0.68-0.85, p < 0.001), and showed predictive power for mediastinal malignancy when using a 0.4 cutoff (OR 6.62, 95%CI 2.98-14.69). Sensitivities and negative predictive values of clinical staging through EBUS-NA attained values ranging between 57% and 92% after FDG-PET, which improved with additional techniques when the tumor had a diameter >3 cm and/or a SUVmax mediastinum/tumor ratio >0.4. The SUVmax mediastinum/tumor ratio is a good predictor of regional tumor extension in NSCLC. This measure is not influenced by intercenter variability and has an accuracy of over 70% for the identification of malignancy when using a 0.4 cutoff.

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.

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: 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.

OBJECTIVES: False-negative results of endobronchial ultrasound-guided transbronchial needle aspiration in non-small-cell lung cancer staging have shown significant variability in previous studies. The aim of this study was to identify procedure- and tumour-related determinants of endobronchial ultrasound-guided transbronchial needle aspiration false-negative results. METHODS: We conducted a prospective study that included non-small-cell lung cancer patients staged as N0/N1 by endobronchial ultrasound-guided transbronchial needle aspiration and undergoing therapeutic surgery. The frequency of false-negative results in the mediastinum was calculated. Procedure-related, first, and tumour-related, second, determinants of false-negative results in stations reachable and non-reachable by endobronchial ultrasound were determined by multivariate logistic regression. RESULTS: False-negative endobronchial ultrasound-guided transbronchial needle aspiration results were identified in 23 of 165 enrolled patients (13.9%), mainly in stations reachable by endobronchial ultrasound (17 cases, 10.3%). False-negative results were related to the extensiveness of endobronchial ultrasound sampling: their prevalence was low (2.4%) when sampling of three mediastinal stations was satisfactory, but rose above 10% when this requirement was not fulfilled (P = 0.043). In the multivariate analysis, abnormal mediastinum on computer tomography/positron emission tomography [odds ratio (OR) 7.77, 95% confidence interval (CI) 2.19-27.51, P = 0.001] and extensiveness of satisfactory sampling of mediastinal stations (OR 0.37, 95% CI 0.16-0.89, P = 0.026) were statistically significant risk factors for false-negative results in stations reachable by endobronchial ultrasound. False-negative results in non-reachable nodes were associated with a left-sided location of the tumour (OR 10.11, 95% CI 1.17-87.52, P = 0.036). CONCLUSIONS: The presence of false-negative ultrasound-guided transbronchial needle aspiration results were observed in nearly 15% of non-small-cell lung cancer patients but in only 3% when satisfactory samples were obtained from three mediastinal stations. False-negative results in stations reachable by endobronchial ultrasound were associated with the extensiveness of sampling, and in stations out of reach of endobronchial ultrasound with left-sided tumours. These results suggest that satisfactory sampling of at least three mediastinal stations by EBUS-TBNA may be a quality criterion to be recommended for EBUS-TBNA staging.

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.

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.

The objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).We studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV(1)]50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.The mean (SD) age of patients was 69 (8) years and the mean FEV(1) was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.Mortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.

Background: Pulmonary nocardiosis is an infrequent infection whose incidence seems to be increasing due to a higher degree of clinical suspicion and the increasing number of immunosuppressive factors. Objective: To study the predisposing factors, clinical characteristics, diagnostic procedures, treatment and progress of pulmonary nocardiosis (PN). Methods: Review of 10 patients (9 male, 1 female, mean age 61) with PN in a 600-bed teaching hospital, diagnosed from 1992 to 1999. Results: Associated diseases observed were chronic obstructive pulmonary disease (COPD) in 6 patients, human immunodeficiency virus (HIV) infection in 3 and polymyalgia rheumatica in 1. Four patients had received oral corticotherapy for COPD for over a year (mean dose 13 mg/day of prednisone or equivalent). The main reason for consultation was an increase in dyspnea in the patients with COPD (6/6) and fever in those with HIV (3/3). Mean time between onset of symptoms and diagnosis was 5 weeks. In 8 patients, the infection occurred outside the hospital setting. The infection was restricted to the lung in 9/10; in the remaining case, the central nervous system (CNS) and subcutaneous tissue were affected. Lobar or multilobar consolidation was the most frequent radiographic pattern found (6/10). Sputum culture was positive when performed (8 cases). Diagnosis was made or confirmed by bronchoscopy (bronchoaspirate or protected specimen brush) in 5 patients. Germs isolated were: Nocardia asteroides (8/10), Nocardia farcinica (1/10), Nocardia otitidiscaviarum (1/10). Cotrimoxazole was the most used empirical treatment (6/10). Resolution was achieved in 5 cases. Four subjects died: 1 HIV patient with disseminated nocardiosis, and 3 COPD patients, 2 of whom had received long-term corticotherapy. Illness recurred in only 1 case, due to failure to comply with treatment. Conclusions: (1) In our geographical setting Nocardia presents as a subacute or chronic pulmonary infection, mainly outside the hospital. (2) It tends to affect only the lung. (3) Diagnosis requires a high clinical suspicion, and can be made on the basis of a sputum culture. (4) Nocardia tends to attack patients with underlying COPD, or immunodepressed patients treated with glucocorticoids, or patients with HIV infection. (5) Mortality is high in both COPD and HIV patients. (6) In our area, cotrimoxazole seems to be the most commonly prescribed treatment.

Community-acquired pneumonia (CAP) is a common illness that still presents substantial morbidity and mortality. In addition to empirical antibiotic therapy and to mechanical ventilatory support (if needed) there are several adjunctive therapies, targeted on reversing certain pathophysiological mechanisms that contribute to increased severity or are associated with complications during the evolution of severe CAP. This chapter reviews the adjunctive therapies currently available, with particular reference to: 1) inflammatory response modulation; 2) pharmacological modulation of abnormal gas exchange; and 3) the effects of body position on gas exchange.

Relationships between pulmonary function testing and high-resolution computed tomography (HRCT) were studied in 39 untreated patients with idiopathic pulmonary fibrosis (IPF) at diagnosis, 23 of whom were followed during 7.5 +/- 0.3 mo (mean +/- SEM). At diagnosis, the extent of overall lung involvement in the HRCT scans showed a moderate but significant correlation only with FVC (r = -0.46, p = 0. 003) and DLCO (r = -0.40, p = 0.03). The extent of ground glass pattern also correlated with FVC (r = -0.58, p = 0.0001). Arterial PO2 at peak exercise (n = 13 patients) showed a significant association with the extent of both ground-glass pattern and overall lung involvement in HRCT (r = -0.60, p = 0.02; and r = -0.64, p = 0. 01, respectively). On multivariate analysis a significant independent correlation between the global disease extent in HRCT and both FVC and DLCO was observed. Changes over time in the total extent of the disease evaluated with HRCT scans were also related to those observed in DLCO and in FVC (r = -0.57, p = 0.01, and r = -0. 51, p = 0.01, respectively). The present study suggests that FVC and DLCO are the physiological variables that best reflect the global extent of disease in IPF and thus may provide significant information for the assessment of the disease's progression.