COPD Clinical Control: predictors and long-term follow-up of the CHAIN cohort.

BACKGROUND: Control in COPD is a dynamic concept that can reflect changes in patients' clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences. METHODS: We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis. RESULTS: 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394-3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern. CONCLUSIONS: The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results. TRIAL REGISTRATION: Clinical Trials.gov: identifier NCT01122758.

[Is the introduction of clinical management programs for patients with chronic obstructive pulmonary disease useful? Comparison of the effectiveness of two interventions on the clinical progress and care received]. / ¿Es útil la implantación de programas de gestión clínica de los pacientes con enfermedad pulmonar obstructiva crónica? Comparación de la efectividad de dos intervenciones sobre la evolución clínica y la atención recibida.

OBJECTIVE: To evaluate the effectiveness of two management programs on patients with chronic obstructive pulmonary disease (COPD). DESIGN: A study with a quasi-experimental design was used to evaluate the effectiveness of two interventions (I1, I2) for the care of patients with COPD after a mean follow-up of 31.2months. SETTING: Primary Care Centres in two Barcelona Health Areas and their referral hospitals. PARTICIPANTS: Patients with COPD selected by simple random sampling using any disease code corresponding to COPD. INTERVENTIONS: I1: Integrated management program that was optimised and coordinated the resources. Training was given, as well as quality control of spirometry. I2: Isolated interventions like a call-centre. Care circuits and computerised clinical notes were shared. MAIN MEASUREMENTS: Variables were recorded as regards lung function, severity, use of inhalers, lifestyles, quality of life, and exacerbations. RESULTS: Of the 393 patients evaluated at the beginning, 120 and 104 (I1 and I2, respectively) received the final evaluation. With I1, there was a reduction in patients who smoked (P=.034). Lung function and quality of life did not change significantly in either group, but shortness of breath was slightly worse. There was an increase in the correct use of inhalers, although it only reached 48% and 61% with interventions I1 and I2, respectively. The percentage of patients with exacerbations decreased with I1 compared to that of I2 (P<.001), and there were less hospital admissions due to exacerbations with I2 compared to I1 (P<.003]). CONCLUSIONS: Both interventions achieved significant improvements, and no overall worsening of a chronic and progressive disease as is COPD.

Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD.

The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD) remains controversial.To evaluate the prevalence and stability of a high level of blood eosinophils (≥300 cells·µL-1) and its relationship to outcomes, we determined blood eosinophils at baseline and over 2 years in 424 COPD patients (forced expiratory volume in 1 s (FEV1) 60% predicted) and 67 smokers without COPD from the CHAIN cohort, and in 308 COPD patients (FEV1 60% predicted) in the BODE cohort. We related eosinophil levels to exacerbations and survival using Cox hazard analysis.In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE cohort had persistently elevated blood eosinophils at all three visits. A significant proportion (43.8%) of patients had counts that oscillated above and below the cut-off points, while the rest had persistent eosinophil levels <300 cells·µL-1 A similar eosinophil blood pattern was observed in controls. Exacerbation rates did not differ in patients with and without eosinophilia. All-cause mortality was lower in patients with high eosinophils compared with those with values <300 cells·µL-1 (15.8% versus 33.7%; p=0.026).In patients with COPD, blood eosinophils ≥300 cells·µL-1 persisting over 2 years was not a risk factor for COPD exacerbations. High eosinophil count was associated with better survival.

Effectiveness of a Respiratory Day Hospital Program to Reduce Admissions for Exacerbation in Patients with Severe COPD: A Prospective, Multicenter Study.

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

Assessment of the internal structure of GOLD 2011 system.

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 introduced a new multidimensional system (symptom/risk) for assessment chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the construct validity of the GOLD 2011 classification strategy; specifically, we evaluated its internal structure in terms of reliability and exploratory factor analysis (EFA). METHODS: Reliability (Cronbach alpha coefficient), correlations between variables and two successive EFA were performed to assess the internal structure of GOLD 2011. Symptoms (mMRC dyspnea score) and risk (number of previous year exacerbations and forced expiratory volume in the first second % of predicted) were selected as variables. RESULTS: The analysis included 679 COPD patients from two Spanish cohorts (71.4 ± 11.7 years). Alpha coefficient of the 3 items was 0.52 for the whole sample. Variables presented statistically significant correlations, but of low to moderate magnitude. A first EFA extracted only one factor accounting 52% of the total variance. A second EFA including four items (the three GOLD 2011 variables plus comorbidities as Charlson index score), extracted two-factors accounting for 65% of the total variance. The first factor included the three items of GOLD 2011, and the second contained only one variable (comorbidities). This solution was stable in patients with different levels of COPD severity. CONCLUSIONS: The available evidence suggests that GOLD 2011 strategy presented a low reliability, and its theorized multidimensionality was not confirm by EFA. Comorbidities appears as a separate and independent domain.

Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience.

INTRODUCTION: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. METHODS: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. RESULTS: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. CONCLUSIONS: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice.

Clinical and Prognostic Impact of Low Diffusing Capacity for Carbon Monoxide Values in Patients With Global Initiative for Obstructive Lung Disease I COPD.

BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored. RESEARCH QUESTION: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients? STUDY DESIGN AND METHODS: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. RESULTS: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined.

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex.

BACKGROUND: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression. RESEARCH QUESTION: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? STUDY DESIGN AND METHODS: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time. RESULTS: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039). INTERPRETATION: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Assessment of a primary and tertiary care integrated management model for chronic obstructive pulmonary disease.

BACKGROUND: The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD) in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care. This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD. The new model will be evaluated in terms of 1) improvement in the rational utilization of health-care services and 2) benefits reflected in improved health status and quality of life for patients. METHODS/DESIGN: A quasi-experimental study of the effectiveness of a COPD management model called COPD PROCESS. The patients in the study cohorts will be residents of neighborhoods served by two referral hospitals in Barcelona, Spain. One area comprises the intervention group (n = 32,248 patients) and the other the control group (n = 32,114 patients). The study will include pre- and post-intervention assessment 18 months after the program goes into effect. Analyses will be on two datasets: clinical and administrative data available for all patients, and clinical assessment information for a cohort of 440 patients sampled randomly from the intervention and control areas. The main endpoints will be the hospitalization rates in the two health-care areas and quality-of-life measures in the two cohorts. DISCUSSION: The COPD PROCESS model foresees the integrated multidisciplinary management of interventions at different levels of the health-care system through coordinated routine clinical practice. It will put into practice diagnostic and treatment procedures that are based on current evidence, multidisciplinary consensus, and efficient use of available resources. Care pathways in this model are defined in terms of patient characteristics, level of disease severity and the presence or absence of exacerbation. The protocol covers the full range of care from primary prevention to treatment of complex cases.

Changes and Clinical Consequences of Smoking Cessation in Patients With COPD: A Prospective Analysis From the CHAIN Cohort.

BACKGROUND: Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD. METHODS: CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. RESULTS: One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV1, 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points. CONCLUSIONS: In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov.

Clinical outcomes of expiratory muscle training in severe COPD patients.

UNLABELLED: The most common symptoms in chronic obstructive pulmonary disease (COPD) patients are breathlessness and exercise limitation. Although both general and inspiratory muscle training have shown clinical benefits, the effects of specific expiratory muscle training remain controversial. OBJECTIVE: To investigate the effects of expiratory training on lung function, exercise tolerance, symptoms and health-related quality of life in severe COPD patients. METHODS: Sixteen patients (FEV(1), 28+/-8% pred.) were randomised to either expiratory muscle or sham training groups, both completing a 5-week programme (30 min sessions breathing through an expiratory threshold valve 3 times per week) (50% of their maximal expiratory pressure (MEP) vs. placebo, respectively). Lung function, exercise capacity (bicycle ergometry and walking test), and clinical outcomes (dyspnoea and quality of life (St. George Respiratory Questionnaire (SGRQ)) were evaluated both at baseline and following the training period. RESULTS: Although lung function remained roughly unchanged after training, exercise capacity, symptoms and quality of life significantly improved. The improvement in both walking distance and the SGRQ score significantly correlated with changes in MEP. CONCLUSION: Our results confirm that a short outpatient programme of expiratory training can improve symptoms and quality of life in severe COPD patients. These effects could be partially explained by changes in expiratory muscle strength.

[Risk factors for mortality in chronic obstructive pulmonary disease]. / Factores de riesgo de mortalidad en la EPOC.

OBJECTIVE: Although the factors predictive of survival in patients with chronic obstructive pulmonary disease (COPD) have been widely studied, full consensus has yet to be reached. The objective of this study was to further clarify how lung function parameters, exercise tolerance, and quality of life influence survival in patients with COPD. PATIENTS AND METHODS: This prospective study included 60 patients diagnosed with COPD. At the start of the study, patients underwent respiratory function tests, exercise testing, and 6-minute walk test. They also answered a chronic respiratory disease questionnaire to measure health-related quality of life. Follow-up lasted 7 years. RESULTS: Five of the 60 patients withdrew from the study. Twenty-six of the remaining 55 patients (47%) died during the study. Univariate Cox regression analysis showed a correlation between survival and age, degree of obstruction, inspiratory capacity, carbon monoxide diffusing capacity, and peak exercise tolerance. No correlation was found between survival and body mass index, PaO2, PaCO2, total lung capacity, residual volume, maximal respiratory pressures, 6-minute walk distance, or health-related quality of life. Age, degree of obstruction (measured as the ratio of forced expiratory volume in 1 second to forced vital capacity after administration of bronchodilator), and maximum minute ventilation in the exercise test were introduced initially in the multivariate Cox stepwise regression analysis, but only maximum minute ventilation remained in the final model (relative risk, 0.926; P< .001). CONCLUSIONS: Our findings show that peak exercise tolerance is the best predictor of survival in patients with COPD.

Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation.

Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.

Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort.

BACKGROUND: Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although its clinical application is difficult. METHODS: To identify patients with ACOS, a cohort of well-characterized patients with COPD and up to 1 year of follow-up was analyzed. We evaluated the presence of specific characteristics associated with asthma in this COPD cohort, divided into major criteria (bronchodilator test > 400 mL and 15% and past medical history of asthma) and minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL, or two separate bronchodilator tests > 200 mL and 12%). We defined ACOS by the presence of one major criterion or two minor criteria. Baseline characteristics, health status (COPD Assessment Test [CAT]), BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, rate of exacerbations, and mortality up to 1 year of follow-up were compared between patients with and without criteria for ACOS. RESULTS: Of 831 patients with COPD included,125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year. Patients with ACOS were predominantly male (81.6%), with symptomatic mild to moderate disease (67%), who were receiving inhaled corticosteroids (63.2%). There were no significant differences in baseline characteristics, and only survival was worse in patients with non-ACOS COPD after 1 year of follow-up (P < .05). CONCLUSIONS: The proposed ACOS criteria are present in 15% of a cohort of patients with COPD and these patients show better 1-year prognosis than clinically similar patients with COPD with no ACOS criteria. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization.

RATIONALE: Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS: We enrolled 45 patients, with mean age (±SD) of 67 (±8) years and mean FEV1 of 41 (±10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS: Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117).

Distribution and Outcomes of a Phenotype-Based Approach to Guide COPD Management: Results from the CHAIN Cohort.

RATIONALE: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. OBJECTIVE: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. METHODS: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. RESULTS: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. CONCLUSIONS: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use.

Identification of airway bacterial colonization by an electronic nose in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Airway bacterial colonization by potentially pathogenic microorganisms occurs in a proportion of patients with Chronic Obstructive Pulmonary Disease (COPD). It increases airway inflammation and influences outcomes negatively. Yet, its diagnosis in clinical practice is not straightforward. The electronic nose is a new non-invasive technology capable of distinguishing volatile organic compound (VOC) breath-prints in exhaled breath. We aim to explore if an electronic nose can reliably discriminate COPD patients with and without airway bacterial colonization. METHODS: We studied 37 clinically stable COPD patients (67.8 ± 5.2 yrs, FEV1 41 ± 10% ref.) and 13 healthy controls (62.8 ± 5.2 yrs, FEV1 99 ± 10% ref.). The presence of potentially pathogenic microorganisms in the airways of COPD patients (n = 10, 27%) was determined using quantitative bacterial cultures of protected specimen brush. VOCs breath-prints were analyzed by discriminant analysis on principal component reduction, resulting in cross-validated accuracy values. Area Under Receiver Operating Characteristics (AUROC) was calculated using multiple logistic regression. RESULTS: Demographic, functional and clinical characteristics were similar in colonized and non-colonized COPD patients but their VOC breath-prints were different (accuracy 89%, AUROC 0.92, p > 0.0001). Likewise, VOCs breath-prints from colonized (accuracy 88%, AUROC 0.98, p < 0.0001) and non-colonized COPD patients (accuracy 83%, AUROC 0.93, p < 0.0001) were also different from controls. CONCLUSIONS: An electronic nose can identify the presence of airway bacterial colonization in clinically stable patients with COPD.