Clinical variables predicting the risk of a hospital stay for longer than 7 days in patients with severe acute exacerbations of chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients may experience an acute exacerbation (AECOPD) that requires hospitalisation. The length of hospital stay (LHS) has a great economic impact on the health-care system. Knowing the predictors of prolonged LHS could help to identify possible interventions. METHODS: We performed a prospective study to identify the clinical predictors of prolonged LHS in patients hospitalised for AECOPD. We divided the study sample by LHS into normal (≤7 days) and prolonged LHS (> 7 days) groups. Outcomes were the need for non-invasive and invasive mechanical ventilation (NIMV and IMV), intensive care unit (ICU) admission, and the 3-year mortality. RESULTS: We enrolled 437 patients, of which 213 and 224 had normal LHS and prolonged LHS, respectively. Patients with a prolonged LHS had more prior hospitalisations for AECOPD, a worse mMRC (modified Medical Research Council) dyspnoea score, a higher prevalence of long-term oxygen therapy and a higher rate of congestive heart disease. During the current admission, this group also tended to require NIMV, IMV and ICU admission and the mortality risks at 6 months, 1 year and 3 years were higher. In the multivariate regression analysis, an mMRC dyspnoea score ≥ 2 (odds ratio-OR 2.24; 95% confidence interval-CI 1.34 to 3.74; p = 0.002) and the presence of acute respiratory acidosis (OR 2.75; 95% CI 1.49 to 5.05; p = 0.001) predicted a prolonged LHS at admission. CONCLUSIONS: The presence of an mMRC ≥2 and acute respiratory acidosis at admission independently increased the risk of a prolonged LHS for AECOPD.

Microorganisms resistant to conventional antimicrobials in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Antimicrobial treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains controversial. In some cases AECOPD are caused by microorganisms that are resistant to treatments recommended by guidelines. Our aims were: 1) identify the risk factors associated with infection by microorganisms resistant to conventional treatment (MRCT), 2) Compare the clinical characteristics and outcomes of patients with AECOPD resulting from MRCT against those with AECOPD from other causes. METHODS: We prospective analysed a cohort of patients admitted with severe AECOPD (2009 to 2015) who were assigned to three groups: patients with MRCT (those patients with germs resistant to antibiotics recommended in guidelines), patients with microorganisms sensitive to conventional antimicrobial treatment (MSCT), and patients with negative microbiology results who had not previously received antibiotics. Multinomial logistic regression analyses were used to examine the associations between microbial aetiology groups and risk factors. The association between LOS and risk factors was also tested in simple and multiple analyses, and similar inclusion criteria were applied for the linear regression analysis. RESULTS: Of the 451 patients admitted, 195 patients (43%) were included. Respiratory cultures were positive in 86(44%) and negative in 109(56%). MRCT were isolated in 34 cases (40%) and MSCT in 52 (60%). Patients with MRCT had more AECOPD in the previous year, received more antibiotic treatment in the previous three months, had more severe disease, higher dyspnoea and a positive respiratory culture in the previous year (mainly for Pseudomonas aeruginosa). The following conditions were independent factors for MRCT isolation: non-current smoker (odds ratio [OR] 4.19 [95% confidence interval [CI] 1.29-13.67], p = 0.017), ≥ 2 AECOPD or ≥ 1 admission for AECOPD in the previous year (OR 4.13 [95% CI 1.52-11.17], p = 0.005), C-reactive protein < 5 mg/dL; (OR 3.58 [95% CI 1.41-9.07], p = 0.007). Mortality rates were comparable at 30-days, one year and 3 years; however, patients in the MRCT group had longer hospital stays. CONCLUSION: In conclusion, there are risk factors for resistant germs in AECOPD; however, the presence of these germs does not increase mortality. Patients with isolation of MRCT had longer length of stay.

Predicting In-Hospital Treatment Failure (≤ 7 days) in Patients with COPD Exacerbation Using Antibiotics and Systemic Steroids.

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.

C-Reactive Protein at Discharge, Diabetes Mellitus and ≥ 1 Hospitalization During Previous Year Predict Early Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

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.

Importance of Aspergillus spp. isolation in Acute exacerbations of severe COPD: prevalence, factors and follow-up: the FUNGI-COPD study.

BACKGROUND: Acute exacerbations of COPD (AECOPD) are often associated with infectious agents, some of which may be non-usual, including Aspergillus spp. However, the importance of Aspergillus spp. in the clinical management of AECOPD still remains unclear. OBJECTIVES: The aims of the study were to analyze the prevalence and risk factors associated with Aspergillus spp. isolation in AECOPD, and to investigate the associated clinical outcomes during a 1-year follow-up period. METHODS: Patients presenting with an AECOPD requiring hospitalization were prospectively included from four hospitals across Spain. Clinical, radiological and microbiological data were collected at admission and during the follow-up period (1, 6 and 12 months after discharge), and re-admissions and mortality data collected during the follow-up. RESULTS: A total of 240 patients with severe AECOPD were included. Valid sputum samples were obtained in 144 (58%) patients, and in this group, the prevalence of Aspergillus spp. isolation was 16.6% on admission and 14.1% at one-year follow-up. Multivariate logistic-regression showed that AECOPD in the previous year (OR 12.35; 95% CI, 1.9-29.1; p < 0.001), concurrent isolation of pathogenic bacteria (OR 3.64; 95% CI 1.65-9.45, p = 0.001) and concomitant isolation of Pseudomonas aeruginosa (OR 2.80; 95% IC, 1.81-11.42; p = 0.001) were the main risk factors for Aspergillus spp. isolation. CONCLUSIONS: The main risk factors for Aspergillus spp. isolation were AECOPD in the previous year and concomitant isolation of Pseudomonas aeruginosa. However, although Aspergillus spp. is often isolated in sputum samples from patients with AECOPD, the pathogenic and clinical significance remains unclear.

Should alternatives to conventional hospitalisation be promoted in an era of financial constraint?

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.

Association Between Rome Classification Among Hospitalized Patients With COPD Exacerbations and Short-Term and Intermediate-Term Outcomes.

BACKGROUND: Recently, the Rome proposal updated the definition of exacerbation of COPD (ECOPD). However, such severity grade has not yet demonstrated intermediate-term clinical relevance. RESEARCH QUESTION: What is the association between the Rome severity classification and short-term and intermediate-term clinical outcomes? STUDY DESIGN AND METHODS: We retrospectively grouped hospitalized patients with ECOPD according to the Rome severity classification (ie, mild, moderate, severe). Baseline, clinical, microbiologic, gas analysis, and laboratory variables were collected. In addition, data about the length of hospital stay and mortality (in-hospital and a follow-up time line from 6 months until 3 years) were assessed. RESULTS: Of the 347 hospitalized patients, 39% were categorized as mild, 31% were categorized as moderate, and 30% were categorized as severe. Overall, patients with severe ECOPD had an extended length of hospital stay. Although in-hospital mortality was similar among groups, patients with severe ECOPD presented a worse prognosis in all follow-up time points. The Kaplan-Meier curves show the role of the severe classification in the cumulative survival at 1 and 3 years (Gehan-Breslow-Wilcoxon test, P = .032 and P = .004, respectively). The multivariable Cox regression analysis showed a higher risk of death at 1 year when patients presented a severe (hazard ratio, 1.99; 95% CI, 1.49-2.65) or moderate grade (hazard ratio, 1.47; 95% CI, 1.10-1.97) compared with a mild grade. Older patients (aged ≥ 80 years), patients requiring long-term oxygen therapy, or patients reporting previous ECOPD episodes had a higher mortality risk. A BMI between 25 and 29 kg/m2 was associated with a lower risk. INTERPRETATION: The Rome classification makes it possible to discriminate patients with a worse prognosis (severe or moderate) until a 3-year follow-up.

Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD.

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.

Predictors of adverse outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease.

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.

FIDEPOC: Consensus on Inspiratory Flow and Lung Deposition as Key Decision Factors in COPD Inhaled Therapy.

Purpose: The pharmacological treatment of chronic obstructive pulmonary disease (COPD) is largely based on inhaled bronchodilators. Inspiratory flow and lung deposition are key parameters to be considered in inhaled therapy; however, the relationship between these two parameters, the patient specificities, and the suitability of the inhaler type for COPD management has not been fully addressed. The present study follows a Delphi Panel methodology to find expert consensus on the role of inspiratory flow and lung deposition as key decision factors in COPD inhaled therapy. Methods: A two-round Delphi Panel, consisting of 38 statements (items) and completed by 57 Spanish pulmonologists, was carried out to measure the experts' consensus degree with each item. Results: A high degree of consensus was reached on most of the items consulted, among these inspiratory flow or inspiratory capacity should be periodically considered when choosing an inhalation device and to ensure the suitability of the inhaler used; the outflow velocity and particle size of the different devices should be considered to ensure adequate lung deposition; an active device (pressurized metered-dose inhalers (pMDI) or soft mist inhalers (SMI)) should be used in patients with low inspiratory flow to achieve adequate lung deposition; and, the use of dry powder inhalers (DPI) should be re-evaluated in patients with severe obstruction and severe exacerbations. Conclusion: This study shows the relevance of inspiratory flow and the degree of particle deposition in the lung in the choice of an inhalation device for COPD management, as well as the convenience of an SMI type device in cases of low inspiratory flow. Moreover, it highlights the scarcity of information on the specific features of inhalation devices in COPD guidelines.

Differences in Drug-Susceptibility Patterns between Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera Clinical Isolates: Prospective 8.5-Year Analysis by Three Laboratories.

Background: It has been suggested that Mycobacterium avium, Mycobacterium intracellulare, and M. chimaera have differential drug susceptibility patterns. We prospectively analyzed and compared the drug susceptibility patterns among these species over an 8.5-year period. Methods: A microdilution method (Slomyco®) was performed for drug susceptibility testing of 402 M. avium, 273 M. intracellulare, and 139 M. chimaera clinical isolates. Results: M. avium showed significantly higher resistance to moxifloxacin, ciprofloxacin, rifampicin, ethambutol, streptomycin, linezolid, cotrimoxazole, and clarithromycin. M. avium also showed higher minimum inhibitory concentrations (MIC) than M. intracellulare and M. chimaera against all drugs except ethionamide, to which M. intracellulare and M. chimaera showed greater resistance. Conclusions: Our series demonstrated differential drug resistance patterns among the most frequent M. avium complex species. M. avium was more resistant than M. intracellulare and M. chimaera versus eight antibiotics and showed greater MIC values to most of the antibiotics studied. These data suggest that knowledge of the local distribution and susceptibility profiles of these pathogens is essential for adequate clinical management.

Age is a determinant of short-term mortality in patients hospitalized for an acute exacerbation of COPD.

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.

Lung Deposition and Inspiratory Flow Rate in Patients with Chronic Obstructive Pulmonary Disease Using Different Inhalation Devices: A Systematic Literature Review and Expert Opinion.

BACKGROUND: Our aim was to describe: 1) lung deposition and inspiratory flow rate; 2) main characteristics of inhaler devices in chronic obstructive pulmonary disease (COPD). METHODS: A systematic literature review (SLR) was conducted to analyze the features and results of inhaler devices in COPD patients. These devices included pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and a soft mist inhaler (SMI). Inclusion and exclusion criteria were established, as well as search strategies (Medline, Embase, and the Cochrane Library up to April 2019). In vitro and in vivo studies were included. Two reviewers selected articles, collected and analyzed data independently. Narrative searches complemented the SLR. We discussed the results of the reviews in a nominal group meeting and agreed on various general principles and recommendations. RESULTS: The SLR included 71 articles, some were of low-moderate quality, and there was great variability regarding populations and outcomes. Lung deposition rates varied across devices: 8%-53% for pMDIs, 7%-69% for DPIs, and 39%-67% for the SMI. The aerosol exit velocity was high with pMDIs (more than 3 m/s), while it is much slower (0.84-0.72 m/s) with the SMI. In general, pMDIs produce large-sized particles (1.22-8 µm), DPIs produce medium-sized particles (1.8-4.8 µm), and 60% of the particles reach an aerodynamic diameter <5 µm with the SMI. All inhalation devices reach central and peripheral lung regions, but the SMI distribution pattern might be better compared with pMDIs. DPIs' intrinsic resistance is higher than that of pMDIs and SMI, which are relatively similar and low. Depending on the DPI, the minimum flow inspiratory rate required was 30 L/min. pMDIs and SMI did not require a high inspiratory flow rate. CONCLUSION: Lung deposition and inspiratory flow rate are key factors when selecting an inhalation device in COPD patients.

Impact of bronchiectasis on outcomes of hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A propensity matched analysis.

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.

Hospitalizations due to exacerbations of COPD: A big data perspective.

BACKGROUND: Patients with Chronic Obstructive Pulmonary Disease (COPD) may suffer episodes of exacerbation (ECOPD) that require hospitalization and worsen their health status, and prognosis. We hypothesized that a detailed interrogation of health-care "big data" databases can provide valuable information to better understand the risk factors and outcomes of these episodes. MATERIAL AND METHODS: We interrogated four databases of the Catalan health-care system (>8,000,000 registries) to identify patients hospitalized because of ECOPD for the first time (index event) between 2010 and 2012. Analysis was carried forward since the index event until the end of 2014 or the death of the patient. The two years that preceded the index event were also investigated. RESULTS: We identified 17,555 patients, (≥50 years of age) hospitalized because of ECOPD (ICD9 v.9 codes at discharge) for the first time between 2010 and 2012. In this population we observed that: (1) 23% of patients die within a year after being discharged from their first ECOPD hospitalization; (2) in the remaining patients, all-cause mortality was related to the number of re-hospitalizations, particularly with early (<30 days) readmissions; (3) despite this being a 'respiratory' cohort, prescription and dispensation of drugs for cardiovascular diseases was higher than for obstructive airway diseases; and, finally, (4) lower winter ambient temperatures are associated with hospital admissions for ECOPD particularly in early re-admitters. CONCLUSIONS: Overall these results indicate under appreciation of the burden of COPD in patients hospitalized for the first time because ECOPD.

Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Readmission for Acute Exacerbation within 30 Days of Discharge Is Associated with a Subsequent Progressive Increase in Mortality Risk in COPD Patients: A Long-Term Observational Study.

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.