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Several factors worsen the prognosis of hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Little is known about the specific contribution of age. Study aim was to evaluate the impact of age on early mortality (90-days). Methods: this observational prospective study considered hospitalized AECOPD patients. Three groups were created according to tertiles of age distribution: group 1 (≤ 67 years), group 2 (68–76 years) and group 3 (≥ 77 years). Baseline, clinical, microbiological, gas analysis and laboratory variables were collected at admission. The primary outcome was mortality at 90 days from admission. Multivariate regression models and receiver-operating characteristic (ROC) curves were used to evaluate the predictive power of age versus early mortality and adjusted for gender, comorbidities, staging and disease severity. Results: we enrolled 449 patients, 33 (7%) of whom died within 90 days from admission. Older patients were predominantly male, with more comorbidities, and higher dyspnoea grade and disease severity. The multivariate logistic regression demonstrated a significant predictive role of age as a continuous variable [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01–1.10; p = 0.046]. The Cox regression analysis found that group 2 [hazard ratio (HR) 6.6; 95% CI 1.5–28.8; p = 0.013], group 3 (HR 7.2; 95% CI 1.6–32.6; p = 0.010) and acute severe hypoxemia at admission (HR 2.7; 95% CI 1.2–6; p = 0.012) were independent significant predictors of mortality. The Kaplan–Meier curves showed a significant role of age in cumulative survival (Gehan–Breslow–Wilcoxon test p = 0.010). ROC curves highlighted 70 years as the best discriminating cut-off. Conclusions: age is a determinant of worse prognosis among hospitalized patients with AECOPD.

Very recently Layden et al. published the first series of 53 patients with acute lung injury associated with the use of e-cigarettes (also known as vaping) in Wisconsin and Illinois (USA) [1]. To our knowledge, only a few cases of e-cigarette, or vaping, associated lung injury (EVALI) have been reported outside the USA (in Canada and Japan) and, so far, none in Europe [2]. Here we present the case of a 31-year-old woman who lived Chicago (Illinois, USA) and arrived in Barcelona (Spain) on vacation from on September 17, 2019 and, as detailed below, suffered EVALI. To our knowledge, this is the first case of EVALI reported in Europe and, given the current world globalisation that allows individuals to travel to other countries easily, highlights the need of being aware of the possibility of encountering, thus diagnosing and treating, a case of vaping-induced acute lung injury outside the US. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Casanova has nothing to disclose. Conflict of interest: Dr. Amaro has nothing to disclose. Conflict of interest: Dr. Soler has nothing to disclose. Conflict of interest: Dr. Sanchez has nothing to disclose. Conflict of interest: Dr. Badia has nothing to disclose. Conflict of interest: Dr. Barbera has nothing to disclose. Conflict of interest: Dr. Agusti has nothing to disclose.

Prescription of antibiotics is wide and generalised in COPD exacerbated patients requiring hospitalisation. Previous data showed that sputum purulence-guided antibiotic treatment strategy might be useful in severe exacerbations. The aim of this study was to investigate the non-inferiority of placebo compared to antibiotic treatment in non-purulent severe exacerbations of COPD. Methods: In this RCT, we recruited a cohort of patients with non-purulent severe exacerbation of COPD. We randomly assigned them to a 5-day course of oral moxifloxacin (400 mg daily) or placebo. The primary outcome was the rate of treatment failure on day 3. Findings: We randomly allocated 73 (25%) patients from the total cohort of 287 evaluated patients with non-purulent exacerbations, and 72 were included in the ITT analysis (35 in the placebo arm and 37 in the moxifloxacin arm). For the primary outcome, 4 patients (11%) in the placebo group and 3 patients (8%) in the moxifloxacin group presented treatment failure (difference 3%, p =0.71; 2-sided 95% CI -0.10-0.17) not reaching the pre-specified non-inferiority failure limit of 15%. We did not observe significant differences between groups in length of stay (LOS) median 6 days (IQR 4-7) in placebo group vs 5 days (IQR 4-7) in moxifloxacin group. Interpretation: In patients with COPD requiring hospitalisation for non-purulent exacerbation, treatment without antibiotic was not inferior to antibiotics in treatment failure or LOS.

The coexistence of both Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis (BE) define an emerging phenotype with a worse prognosis; however, data about these patients do not consider baseline characteristics as confounders. We evaluate the impact of BE on outcomes of hospitalized patients with acute exacerbation of COPD (AECOPD). We prospectively considered AECOPD patients, analysed using a propensity score matching (PSM) method. The outcomes included length of hospital stay, use of non-invasive and invasive mechanical ventilation, intensive care unit admission, and mortality up to 3-years. Out of the 449 patients enrolled, 160 had associated BE. AECOPD with BE were older, had lower body mass index and greater functional impairment and severity of symptoms than AECOPD without BE. After PSM, 91 patients were considered for each group and no significant differences were found for all baseline characteristics. In full cohort, the cumulative mortality rate, the survival time, the Kaplan-Meier survival curves and the risk of death were worse in AECOPD with BE in the follow-up of 6-months, 1-year and 3-years. After PSM, data on mortality were similar between AECOPD with and without BE. In conclusion, in AECOPD patients the presence of BE does not influence mortality in a long-term follow-up.

Despite well established clinical guidelines, performance of long-term oxygen therapy (LTOT) programs shows marked variability among territories. The current study assessed the LTOT program and the health status of patients on LTOT prior to the deployment of community-based integrated care in an urban health district of Barcelona (Spain).To assess: i) the LTOT program and health status of the patients on LTOT in the health district; ii) their frailty profile; and, iii) the requirements for effective deployment of integrated care services for these patients.Cross-sectional observational study design including all patients (n = 406) on LTOT living in the health district. Health status, frailty, arterial blood gases, forced spirometry and hand-grip muscle strength were measured. Network analysis of frailty was carried out.Adequacy of LTOT prescription (n = 362): 47% and 31% of the patients had PaO2 ≤ 60 mmHg and ≤55 mmHg, respectively. Adherence to LTOT: 31% of all patients used LTOT ≥15 h/d; this figure increased to 67% in those with PaO2≤60 mmHg. Assessment of frailty: Overall, LTOT patients presented moderate to severe frailty. Care complexity was observed in 42% of the patients.Adequacy and adherence to LTOT was poor and many patients were frail and complex. The outcomes of the network analysis may contribute to enhance assessment of frailty in LTOT patients. These observations suggest that an integrated care strategy has the potential to improve the health outcomes of these patients.

Background: The coexistence of both Chronic Obstructive Pulmonary Disease (COPD) and Non-Cystic Fibrosis Bronchiectasis (NCFB) has been recently defined as an emerging phenotype of patients who experience a worse prognosis; however, data about these patients do not consider baseline variables as cofounders. Objective: The objective of our prospective study was to evaluate the role of NCFB on the clinical impact and prognosis of hospitalized patients with Acute Exacerbation of COPD (AECOPD). Methods: Data were analysed by a propensity score matching (PSM) and divided in AECOPD without and with NCFB. Clinical, laboratory, microbiological, and severity data were evaluated at admission and at day 3 of hospitalization. Data on prognosis were recorded in the follow-up of 30 days, 6 months, 1 year and 3 years. Results: Of 449 consecutive AECOPD patients enrolled, 105 had associated NCFB. AECOPD patients with NCFB were older, with a lower body mass and a greater impairment on functional, symptoms and questionnaire-reported severity characteristics than AECOPD without NCFB. After PSM, 104 patients were considered for each group and no significant differences were found in all baseline characteristics. In full cohort the cumulative mortality rate, the risk of death and the time to death were worse in AECOPD with NCFB (Gehan-Breslow-Wilcoxon test p=0.007, p=0.001, p=0.003 in the follow-up of 6 months, 1 year and 3 years, respectively). After PSM data about mortality were similar between AECOPD with and without NCFB. Conclusion: After elimination of confounding factors, our study demonstrates that the presence of NCFB does not influence the risk of death in a long-term follow-up.

Recurrent hospitalizations in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients have clinical and economic consequences; particularly those readmitted soon after discharge. The aim of our observational study was to determine predictors of early readmission to hospital (30 days from discharge). Prospective data on 125 hospitalized AECOPD patients were collected over a 30-month period at two Spanish university hospitals. Based on readmission after discharge, patients were divided into non-readmitted (n = 96) and readmitted (n = 29). Measures of serum inflammatory biomarkers were recorded on admission to hospital, at day 3 and at discharge; data on clinical, laboratory, microbiological and severity features were also recorded. In a multivariate model, C-reactive protein (CRP) at discharge ≥ 7.6 mg/L, presence of diabetes and ≥ 1 hospitalization for AECOPD during previous year were significant risk factors for predicting readmission. Presence of all 3 risk factors perfectly identified the readmitted patients (positive and negative predictive values of 1.000; 95% CI, 1.00-1.00). A combination of 3 readily available clinical and biochemical parameters is accurate in identifying hospitalized AECOPD patients at risk for early readmission.

Background: Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the infl ammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP 1 COPD. Methods: Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n 5 133) and patients with CAP 1 COPD (n 5 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. Results: Patients with CAP 1 COPD had higher FEV 1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP 1 COPD had signifi cantly ( P , .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor- a , and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confi rmed higher levels of the same biomarkers in patients with CAP 1 COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP 1 COPD. Conclusions: Our study confi rms that two different clinical and infl ammatory profi les exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.

To the Editor: Obstructive sleep apnoea/hypopnea (OSAH) is a highly prevalent disease that increases the risk of cardiovascular, metabolic and neurocognitive disorders [1, 2]. Generally speaking, when OSAH is suspected primary care physicians refer the patient to a hospital sleep unit to assess the clinical history and decide the optimal sleep test for confirming the diagnosis [3]. In recent years there has been an increase in the demand for consultations and diagnostic studies in sleep units [4], resulting in long waiting lists. Therefore, new strategies are needed in order to improve the management of this disease. We consider that an ideal system would consist of an integrated network involving sleep units and primary care centres, which would permit a detailed classification of patients and reduce excessive delay for those with severe symptoms. Accordingly, the aim of the study was to demonstrate that in suspected sleep apnoea patients the initial assessment and the appropriate sleep test would be similar whether they were undertaken by a trained general pulmonologist in a primary care centre or by a sleep physician. Our hospital has developed a new model of integrated care involving hospital sleep units and primary care centres, governed by a shared clinical protocol. The major premises for this model are: 1) when a family physician suspects OSAH, he or she sends the patient to a primary care pulmonologist, who has a basic knowledge of sleep medicine, as well as chronic obstructive pulmonary disease, asthma, etc. ; 2) the pulmonologist (second level of health attention) assesses the patient and decides the type of sleep study required, according to the aforementioned common protocol; 3) the patient is referred to the sleep unit to perform the diagnostic study, and continuous positive airway pressure (CPAP) titration when required (normally …

Background Because the current economic crisis has led to austerity in health policies, with severe restrictions on public health care, avoiding unnecessary admissions and shortening hospital stays is rapidly becoming an urgent priority. Alternatives to hospitalisation replace or shorten hospital processes, including diagnosis, monitoring, treatment and follow-up. This review aims to present the available evidence on alternatives to conventional hospitalisation for medical disorders; options for surgery, psychiatry and palliative care are largely excluded. Materials and methods Narrative review. Results The main alternatives to conventional hospitalisation include day centres (DC), quick diagnosis units (QDU), hospital at home (HaH) and, in some circumstances, telemonitoring. DC increase patient comfort, reduce costs and can improve efficiency. In generally healthy patients with suspected severe disease, QDU may be a good alternative to hospitalisation for diagnostic procedures. However, their cost-effectiveness remains to be clearly proven. Randomised controlled trials have shown that hospital-at-home (HaH) can lead to earlier hospital discharges, improve outcomes and reduce costs in patients with prevalent chronic diseases. Although telemonitoring seems to be promising and its use is increasing, methodologically sounder studies with a higher level of evidence are needed to assess its clinical effectiveness. Conclusions Factors such as ageing, the need for an earlier diagnosis of suspected severe disease, the increasing complexity of medical care and the increasing costs of hospitalisation mean that, whenever possible, giving priority to less expensive alternatives to hospital admission, such as QDU, DC, HaH and telemedicine, is an urgent task in the current economic crisis.

Hospital admissions due acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a negative effect on physical activity since the latter is reduced both during hospitalization and for a relatively prolonged period after discharge. To prevent the effects of deconditioning we conducted a randomized clinical trial ( NCT01871025 ) using a step exercise protocol from the third day of hospital admission until one month after discharge. We recruited 22 consecutive patients hospitalized with AECOPD, who were randomized to an early intervention with step exercises (Chester Step Test) (intervention group, IG) or usual care (physiotherapy techniques for airway clearance, etc.) (n=11 in each group). The primary outcome was the level of physical activity four weeks after discharge. Patients had [mean (SD)] 67 (8) yrs. and were mostly male (82%), former smokers (70%) and frequent exacerbators (31%). FEV 1 was 33(11) % pred. and CAT reached 24(8) points. The median length of hospital stay was similar in both groups (6 days). One month after discharge, the time spent sitting per day was only significantly reduced in the IG (13 to 7 hours/day, p=0.007). In addition, the percentage of patients doing moderate to vigorous activity (>3 MET) more than 150 minutes/week was significantly higher in the IG compared with the usual care group (56 vs. 12%, p=0.04). Moreover, the number of steps per day showed a trend to also be higher in the former group (4282 vs. 2835, respectively). In conclusion, the use of an early intervention with step exercises during hospital admission and the recovery period improved the level of daily physical activities in patients with AECOPD one month after discharge.

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD., The NLRP3 inflammasome is primed in stable COPD lungs, then activated during infectious exacerbation http://ow.ly/Wopi300DXcT

Background and Objective Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. Methods The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. Results Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51–4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10–5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). Conclusion In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death.

Aspergillus fumigatus is the most prevalent airborne fungal pathogen in developed countries, responsible for a broad spectrum of illness, from saprophytic colonization of lower airways to invasive and life-threatening disseminated pulmonary diseases. Patients with severe chronic obstructive pulmonar

Chronic obstructive pulmonary disease (COPD) is a chronic disease causing increasing healthcare costs worldwide. Another respiratory disease causing high costs and morbidity is community-acquired pneumonia (CAP). Because of the constant growth in the population with both diseases (CAP and COPD), analyzing their clinical characteristics is important. Several cellular factors are known to contribute to differences in clinical expression: some lead to COPD exacerbations while others lead to symptoms of pneumonia. The use of new biomarkers (procalcitonin, pro-adrenomedullin and copeptin) help to distinguish among these clinical pictures. To decrease morbidity and mortality, clinical guidelines on antibiotic therapy must be followed and this therapy should be prescribed to patients with CAP and COPD. There are also prevention measures such as the pneumococcal vaccine whose role in the prevention of pneumococcal CAP should be further studied. The present review aims to elucidate some of the above-mentioned issues.

SummaryBackgroundChanges in management of COPD in primary care were studied following a training exercise among Spanish general practitioners (GPs). The exercise involved dissemination of the Spanish Society for Pulmonology and Thoracic Surgery (SEPAR) guidelines. The use of a portable device to perform spirometry tests was evaluated to adequately categorize COPD and reduce other diagnostic interventions.MethodsA representative sample of GPs from general practices in Spain was recruited for the study. In phase I, GPs performed an initial evaluation of 5 patients with COPD. In phase II, GPs were randomly allocated to the following groups: 1) control group-G1 (GPs managing COPD according to usual clinical practice); 2) training group-G2 (dissemination of SEPAR guidelines); and 3) training group-G3 (dissemination of SEPAR guidelines and distribution of the Koko Peak Pro to measure FEV1, FEV6, and FEV1/FEV6).ResultsPhase-I included 3254 physicians, who selected 16,024 patients. In phase II, 301 physicians in G1, 1182 in G2, and 1141 in G3 selected 1481, 5798, and 5556 patients respectively. Evaluation of the changes in COPD stratification according to the SEPAR guidelines showed that physicians in G1 adequately classified 60% of patients, compared to 69% in G2 and 88.5% in G3 (p

Short-acting beta(2)-agonists are one of the mainstays of bronchodilator strategy for exacerbations of chronic obstructive pulmonary disease (COPD). The assessment of pulmonary gas exchange after salbutamol in COPD severe exacerbations remains unknown.We investigated whether the effects of nebulized salbutamol during COPD severe exacerbations are associated with further deterioration of pulmonary gas exchange.We examined patients with severe COPD when hospitalized for exacerbation (n = 9), and while in stable convalescence.We assessed spirometry, arterial blood gases, systemic hemodynamics, and V/Q relationships 30 and 90 minutes after administration of 5.0 mg salbutamol. At exacerbation, compared with baseline, 30 minutes after salbutamol administration, cardiac output (Q) increased (from 6.5 +/- [SEM] 0.4 to 7.3 +/- 0.5 L . min(-1)) (p0.03) alone, without inducing changes in gas exchange indices. When in convalescence, compared with baseline, 30 minutes after salbutamol, there was an increase in Q (from 5.7 +/- 0.5 to 7.0 +/- 0.6 L . min(-1)) and Vo(2) (from 211 +/- 12 to 232 +/- 11 ml . min(-1)) (p0.002 each), whereas Pa(O(2)) decreased (from 71 +/- 4 to 63 +/- 3 mm Hg) and alveolar-arterial Po(2) difference increased due to increased perfusion of low-V/Q-ratio regions (from 4.5 +/- 2.6 to 9.6 +/- 4.1% of Q) (p0.05); Sa(O(2)) (93 +/- 2%) and Pa(CO(2)) (43 +/- 2 mm Hg) remained unchanged. This deleterious gas exchange response persisted at 90 minutes.At exacerbation, salbutamol does not aggravate pulmonary gas exchange abnormalities. When in convalescence, however, baseline lung function improvement was associated with a detrimental gas exchange response to salbutamol, resulting in further V/Q imbalance and small decreases in Pa(O(2)) compounded by small increases in Q and Vo(2).

Antibiotics are commonly prescribed in exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of bacteria in these exacerbations is controversial.To identify clinical predictors of bacterial infection as a cause of exacerbation, considering the protected specimen brush (PSB) as the gold standard.Clinical data, sputum and PSB samples were collected from 40 patients with COPD requiring hospitalisation due to severe exacerbations who had not received previous antibiotic treatment.Quantitative cultures of PSB samples (n = 40) yielded 23 potential pathogenic microorganisms (PPMs) at concentrations ofor =10(2) colony-forming units/ml in 18 (45%) patients. Sputum samples were obtained from all 40 patients. Culture of good-quality sputum samples (n = 18) yielded 16 PPMs corresponding to 14 (35%) patients. The concordance between the PSB and sputum rate was high (kappa = 0.85, p0.002). The self-reporting patient observation of sputum purulence (odds ratio (OR) 27.20 (95% confidence interval (CI) 4.60 to 60.69), p = 0.001), the percentage predicted forced expiratory volume in 1 s (FEV(1)%)50 (OR 2.27 (95% CI 1.55 to 3.21), p = 0.014),4 exacerbations in the past year (OR 6.9 (95% CI 0.08 to 1.08), p = 0.028) and previous hospitalisations due to COPD (OR 4.13 (95% CI 1.02 to 16.07), p = 0.041) were associated with the presence of PPMs in the distal airways. The operative characteristics for predicting distal airway infection when patients presented with purulent exacerbation were as follows: sensitivity 89.5%, specificity 76.2%, positive predicted value 77.3% and negative predicted value 88.9%.The self-reporting presence of purulence in the sputum, as well as common previous exacerbations and hospitalisations due to COPD in patients with severe airflow obstruction (FEV1%50) predict the presence of bacterial infection in the distal airways. The use of these clinical variables may help in selecting candidates to receive antibiotic treatment.

Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (≤ 7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95% CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role.

Background: A 30-day readmission to hospital for COPD exacerbation (COPDE) occurs in about 20% of patients, with clinical and economic impact. Data on prognosis of these patients readmitted earlier are poorly understood. Objective: to evaluate the effect of a early COPDE occurring in a period of 30 days after discharge and requiring hospitalization on prognosis of patients. Design: A prospective observational study in a university hospital in Spain. Patients: Based on the presence of a new readmission for COPDE within 30 days of discharge, the study cohort (n=378) was divided into patients with (n=68) and without (n=310) a 30-day readmission. Main Measures: Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospitalization; mortality data were determined by evaluating three follow-up periods: 6 months, 1 year and 3 years. Key Results: Patients with a 30-day readmission had worse lung function, dyspnea perception and clinical severity. ≥2 prior COPDE (HR, 2.47; 95% CI, 1.51 to 4.05) was the only variableindependently associated with a 30-day readmission. Analyses of prognosis in all follow-up periods showed higher rate of mortality for patients with 30-day readmission in comparison to patients without; moreover 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10 to 5.59). In patients with a 30-day readmission, the estimated absolute increase in risk of 6-months death was 17% (number needed to harm [NNH], 6), 1-year death was 19% (NNH, 6) and 3-years death was 24% (NNH, 5). Conclusion: A 30-day readmission influences the risk of mortality in patients with COPDE.

Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids.Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded.At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P.01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02).Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation.

The diagnosis of small peripheral lung cancer is difficult to achieve by non-invasive methods. We hypothesized that in these patients induced sputum might increase the diagnostic yield over spontaneous sputum, representing a good diagnostic alternative in selected patients. We prospectively evaluated 60 patients with peripheral lung lesions and normal bronchoscopic evaluation. Six samples of sputum (three spontaneous and three induced with nebulization of hypertonic saline) before bronchoscopy and six samples of sputum after bronchoscopy (three spontaneous and three induced) were obtained in each subject. Forty-two out of the 60 patients included were finally diagnosed with lung cancer. Eighteen patients were diagnosed with different benign conditions of the lung. Overall, malignant cells in sputum were observed in 21 patients and in all but one, the final diagnosis of lung cancer was achieved. Only one patient with a pseudoinflammatory tumour of the lung had a false-positive result in one spontaneous sputum sample. The diagnosis of lung cancer was obtained in 18 patients with the induced sputum (43%) and in 14 patients with spontaneous sputum (31%) (P=NS). Samples of induced sputum were more adequate for cytological analysis than samples of spontaneous sputum (P

La historia natural de la enfermedad pulmonar obstructiva cronica (EPOC) se caracteriza por la aparicion de episodios repetidos de agudizacion (AEPOC), que se manifiestan como un cambio en la situacion clinica basal del paciente, junto a un incremento de los sintomas respiratorios. Aunque no hay una clara definicion de AEPOC, sabemos que estos episodios se desencadenan por una gran variedad de factores, en su mayoria agentes infecciosos como virus o bacterias y, aunque con menor frecuencia, por otros agentes ambientales desconocidos. Si bien la experiencia demuestra que tanto los corticoides como los antibioticos tienen efectos beneficiosos en el tratamiento comun de las agudizaciones, todavia no se conoce ningun parametro clinico o biologico capaz de determinar de forma precisa la etiologia de las agudizaciones. En los ultimos anos, el papel que desempenan diferentes marcadores sistemicos en los mecanismos de respuesta inflamatoria que se observan en las AEPOC esta adquiriendo una consideracion cada vez mayor. La descripcion de estos marcadores biologicos circulantes resulta de vital importancia si finalmente detectan con seguridad aquellas agudizaciones cuya causa puede requerir un tratamiento especifico. Esta cuestion estaria relacionada con la utilidad practica de determinados marcadores en un aspecto clinico tan relevante como es la decision final de administrar o no tratamiento antibiotico en los episodios de agudizacion1. Una encuesta epidemiologica llevada a cabo en 360 hospitales de EE.UU., que incluyo a un total de 69.820 pacientes hospitalizados por AEPOC, mostro que un 85% habia recibido tratamiento antibiotico2. Una encuesta similar efectuada en varios paises europeos (Espana, Francia, Reino Unido e Italia), sobre una cohorte de 600 pacientes con AEPOC hospitalizados, mostro que mas del 80% eran finalmente tratados con antibioticos (datos no publicados). La informacion aportada por estos estudios epidemiologicos permite concluir que la utilizacion de antibioticos en las agudizaciones que requieren hospitalizacion es una practica muy generalizada. Sin embargo, aunque la prescripcion de antibioticos en las AEPOC es casi universal, no hay una evidencia clara de su eficacia en todos los casos, dado que en algunos estudios controlados queda demostrado su beneficio, mientras que en otros este beneficio resulta mas bien escaso. Por otra parte, es bien conocido que el uso incontrolado de antibioticos en este escenario incrementa el gasto sanitario y contribuye a empeorar la tasa de resistencias bacterianas3. Este problema es particularmente importante en los pacientes ancianos, en los que presentan un deterioro mas grave de la funcion pulmonar, tienen otras enfermedades concomitantes o experimentan frecuentes episodios de agudizacion que a menudo requieren hospitalizacion. En un reciente metaanalisis que reviso sistematicamente los resultados de 11 estudios aleatorizados y controlados con placebo, llevados a cabo entre los anos 1966 y 2005, se concluia que el uso de antibioticos tenia un claro beneficio en las AEPOC caracterizadas por un incremento del volumen de expectoracion y la presencia de purulencia en el esputo4. En estos casos, la utilizacion de antibioticos reducia claramente el riesgo de muerte a corto plazo en un 77% y la tasa de fracasos terapeuticos en un 53%. En general, se observo el beneficio de los antibioticos en el grupo de pacientes con EPOC de moderada a grave y, como cabia esperar, en los casos que requerian hospitalizacion. Estos resultados, sin embargo, deben interpretarse con cautela, dado que el analisis incluye estudios con importantes diferencias tanto en los criterios de seleccion de los pacientes como en la eleccion del tipo de antibiotico. En resumen, hasta el momento no hay ningun ensayo clinico con un diseno apropiado que haya evaluado el beneficio de no prescribir antibioticos en las AEPOC no purulentas, a pesar que este constituye un grupo significativo de pacientes que acaban siendo hospitalizados. La determinacion de la etiologia infecciosa de las AEPOC se ha convertido en un desafio constante para los investigadores que trabajan en este campo, dado que la mayoria de los estudios que intentan demostrar la relacion entre agudizacion e infeccion bacteriana se apoyan en el cultivo de las muestras de esputo, tecnica cos202.929

We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.

In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However, the pattern of colonization differs among groups studied. The knowledge of different colonization patterns may be important for future antibiotic prophylactic strategies and for the empirical antibiotic regimens when exacerbations occur in these patients.

From the authors: We thank D. Aggarwal and co-workers for their interest in our recently published paper regarding a sputum purulence-guided strategy of antibiotic treatment in patients with exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospitalisation [1]. Their comments highlight important issues relating to the discrepancies reported in the literature about the relationship between sputum colour and the presence of pathogenic bacteria in the lower respiratory tract. First, the question of whether isolation of bacteria from the sputum of patients with COPD is or is not directly related to exacerbations is still a subject of controversy. Classically, the Anthonisen criteria ( i.e . increased dyspnoea, sputum production and sputum purulence) have been considered the most reliable predictors of bacterial infection as a cause of exacerbation [2]. Moreover, the most relevant advance in our ability to predict bacterial …

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.

Background: It is crucial to identify risk factors for poor evolution of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) in order to provide adequate intensive therapy and closer follow-up. Objectives: To identify predictors of adverse outcomes in patients hospitalised for exacerbation of COPD. Methods: A prospective, observational study was conducted in patients admitted for exacerbation of COPD. Demographic and clinical parameters were evaluated, including different multidimensional prognostic scores. Adverse outcomes included the following: death during hospitalisation or 1-month follow-up, intensive care unit admission, invasive or non-invasive mechanical ventilation, prolonged hospitalisation (>11 days) and COPD-related emergency visit or readmission within 1 month after discharge. Univariate and multivariate analysis were performed. Results: Of 155 patients included, an adverse outcome occurred in 69 (45%). Patients with an adverse outcome had lower forced expiratory volume in 1 s (p = 0.004) and more frequent exacerbations (p = 0.011), more frequently used oxygen at home (p = 0.042) and presented with lower pH (p < 0.001), lower ratio of arterial oxygen pressure to the fraction of inspired oxygen (p = 0.006), higher arterial carbon dioxide pressure (p < 0.001) and a worse score on several prognostic indices at admission. Independent predictors of adverse outcome were exacerbation of COPD in the previous year [odds ratio 3.9, 95% confidence interval (CI) 1.6–9.9; p = 0.004], hypercapnia (odds ratio 9.4, 95% CI 3.7–23.6; p < 0.001) and hypoxaemia (odds ratio 4.3, 95% CI 1.5–12.6; p = 0.008). In the presence of all three characteristics, the probability of an adverse outcome was 95%, while hypercapnia was the strongest prognostic factor with a risk of 54%. Conclusions: Patients with previous exacerbation of COPD, hypercapnia and hypoxaemia had the highest risk of an unfavourable evolution. The calculation of prognostic indices did not provide additional discriminative power.

The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established.To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling.Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82).One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.

Background: A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)). Methods: BAL fluid cell numbers and levels of tumour necrosis factor (TNFα) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples. Results: Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-κB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p

To study microbial and susceptibility patterns and antimicrobial treatment responses in patients with severe, acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation.Microbial investigation using tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage, as well as paired serologies. Evaluation of antimicrobial treatment by results of the initial investigation, susceptibility testing, and a repeated microbial investigation (tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage) after 72 hrs.A respiratory intensive care unit of a 1,000-bed teaching hospital.Fifty severely exacerbated and mechanically ventilated patients with chronic obstructive pulmonary disease.Initial empirical antimicrobial treatment according to clinical judgment.Overall, 36 of 50 patients (72%) had evidence of a microbial origin. Community-acquired endogenous pathogens were present in 70% of patients, and Gram-negative enteric bacilli and Pseudomonas/Stenotrophomonas species were present in 30%. All five isolates of Streptococcus pneumoniae were resistant to penicillin (three intermediately and two highly), and three were resistant to multiple antibiotics. Pseudomonas species revealed multiresistance in four of nine isolates (44%), and Stenotrophomonas maltophilia revealed multiresistance in one of two isolates. Antimicrobial treatment was modified according to diagnostic results in 11 of 31 patients (36%) with potentially pathogenic microorganisms. In patients who underwent a repeat investigation after 72 hrs, 24% of the initially present and potentially pathogenic microorganisms persisted. Inappropriate initial antimicrobial therapy was associated significantly with bacterial persistence (p.002).Considering the diversity of microbial pathogens and the resistance rates especially to S. pneumoniae in this patient population, antimicrobial treatment should be based on the constant study of local microbial and susceptibility patterns along with routine microbial investigation of the individual patient.

Severity criteria for exacerbations of chronic obstructive pulmonary disease (COPD) have not yet been defined as they have for pneumonia. Therefore, investigators have usually adopted pragmatic criteria to define their study populations according to the subject of the study. For example, studies addressing modalities of ventilatory support have used acute severe hypoxemia and/or hypercapnic failure as entry criteria [1-5]. Most studies evaluating antimicrobial treatment have characterized the populations studied by the severity of airflow limitation in stable states and/or during exacerbations [6-9]. However, patients with severe airflow limitation (e.g. forced expiratory volume in one second - FEV1 - < 35% predicted) in stable states or during an exacerbation may or may not present with acute respiratory failure and vice versa. On the other hand, a recent study has provided evidence that patients with severe airflow limitation may be more likely to have an infection by gram-negative enterobacteriaceae (GNEB) or Pseudomonas aeruginosa [9] but it is not known whether the type of pathogen independently predicts severe exacerbations.

The effect of bacterial colonization of the bronchi on the progress of airflow limitation is not well known. Therefore, the pattern of airway inflammation in smokers and patients with stable chronic obstructive pulmonary disease (COPD) and its relation to bronchial microbial colonization was assessed. Eight nonsmoking and 18 smoking controls as well as 52 patients with COPD (28 mild, 11 moderate and 13 severe) were studied. All subjects were investigated by means of flexible bronchoscopy including protected specimen brush and bronchoalveolar lavage (BAL) sampling. Differential cell counts, cytokine (interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha(TNF-alpha) concentrations and microbial patterns were determined in BAL fluid. Forced expiratory volume in one second (FEV1) % of the predicted value was inversely correlated with pack-yrs of cigarette smoking (r=-0.47, p

Langerhans’ cell histiocytosis (LCH) is a proliferative histiocytic disorder of unknown origin. The lesions of LCH contain single or multifocal proliferation of histiocytes similar in phenotype to dendritic Langerhans’ cells (1). The disorder ranges in clinical severity from a solitary eosinophilic granuloma of bone to a generalised disease with multiple organ involvement. Primary involvement of the lung is rare and only few isolated cases have been reported (2). Occasionally, pulmonary LCH has been reported to be associated with Hodgkin’s disease (3); the underlying pathogenic mechanism of such association remains unknown. Here, we report the case of a 19-year-old patient who developed pulmonary LCH 2 months after receiving an autologous haemopoietic progenitor cell transplantation (AHPCT) for Hodgkin’s disease.