Concepción Montón

Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

Background The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD). Methods We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy. Results Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations. Conclusion Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD.

Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

BackgroundPatients 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.MethodsA 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.ResultsP. 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.ConclusionsThe 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.

Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients

Abstract Background: 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. Methods: Thirty-two patients aged ≥18 years with obstructive airway disease and FEV1 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. Intervention: blood analysis every six months; spirometry and nitric oxide measurement at every visit. Results: 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. FEV1 (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. Conclusion: 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.

Causas de muerte en pacientes con EPOC grave. Factores pronósticos

OBJECTIVE 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). PATIENTS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Functional Metagenomics of the Bronchial Microbiome in COPD

The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance. The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation. Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data. Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation. Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations. Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2–2.3) vs 3.6 (3.3–6.9), p = 0.012; and 1.8 (0–3.3) vs 3.6 (1.8–5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0–1.5) vs 0 (0–0.5), p = 0.043; and 7 (6.4–9) vs 5.9 (6.3–6.1), p = 0.012 respectively]. In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways.

Determinants of false-negative results in non-small-cell lung cancer staging by endobronchial ultrasound-guided needle aspiration

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.

C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity

Background C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. Methods A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. Results A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. Conclusion CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease.

Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

Abstract Objective 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). Patients and methods We studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV1] Results The mean (SD) age of patients was 69 (8) years and the mean FEV1 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. Conclusions 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.

COPD is a clear risk factor for increased use of resources and adverse outcomes in patients undergoing intervention for colorectal cancer: a nationwide study in Spain

Background We hypothesized that patients undergoing surgery for colorectal cancer (CRC) with COPD as a comorbidity would consume more resources and have worse in-hospital outcomes than similar patients without COPD. Therefore, we compared different aspects of the care process and short-term outcomes in patients undergoing surgery for CRC, with and without COPD. Methods This was a prospective study and it included patients from 22 hospitals located in Spain – 472 patients with COPD and 2,276 patients without COPD undergoing surgery for CRC. Clinical variables, postintervention intensive care unit (ICU) admission, use of invasive mechanical ventilation, and postintervention antibiotic treatment or blood transfusion were compared between the two groups. The reintervention rate, presence and type of complications, length of stay, and in-hospital mortality were also estimated. Hazard ratio (HR) for hospital mortality was estimated by Cox regression models. Results COPD was associated with higher rates of in-hospital complications, ICU admission, antibiotic treatment, reinterventions, and mortality. Moreover, after adjusting for other factors, COPD remained clearly associated with higher and earlier in-hospital mortality. Conclusion To reduce in-hospital morbidity and mortality in patients undergoing surgery for CRC and with COPD as a comorbidity, several aspects of perioperative management should be optimized and attention should be given to the usual comorbidities in these patients.

Clinical and Safety Outcomes of Long-Term Azithromycin Therapy in Severe COPD Beyond the First Year of Treatment

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.