Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship

Prevalence of different comorbidities in COPD patients by gender and GOLD stage

BACKGROUND: Several comorbidities frequently affect COPD progression. Aim of the study was to assess the prevalence of main comorbidities by gender and disease severity in a cohort of COPD patients referring for the first time to a specialist institution. METHODS: The study was a non-interventional, cross-sectional investigation carried out via automatic and anonymous selection from the institutional data base over the period 2012–2015. Inclusion criteria were: subjects of both sex aged ≥40 years; diagnosis of COPD according to GOLD guidelines 2014; the availability of a complete clinical record file. Variables collected were: lung function; smoking history; BMI; the Charlson Comorbidity Index (CCI); number and kind of comorbidities for each patient. RESULTS: At least one comorbidity of clinical relevance was found in 78.6 % of patients, but at least two in 68.8 %, and three or more were found in 47.9 % of subjects. Mean CCI was 3.4 ± 1.6sd. The overall prevalence was 2.6 comorbidities per patient, but 2.5 in males, and 3.0 in females, respectively (p < 0.05). Cardio-vascular disorders were the most frequent, but significantly more frequent in males (44.7 vs 30.7 %, respectively), while the metabolic, the digestive and the osteo-articular disorders were prevailing in females (12.4 vs 9.2; 14.2 vs 4.8, and 6.0 vs 3.8, respectively). In particular, chronic cor pumonale and arrhythmias mainly prevailed in men and congestive heart failure in females, while arterial hypertension resulted equally distributed. As concerning respiratory disorders, pneumonia, pleural effusions and chronic respiratory failure were more frequently found in men, while bronchiectasis and asthma-COPD overlap syndrome (ACOS) in females. Anaemia, gall bladder stones, osteoporosis and spontaneous fractures mostly prevailed in females, while gastric disorders of inflammatory origin and arthrosis were more frequent in males. Cognition disorders, dementia and signs of degenerative brain disorders were more frequently found in men, while depression in females. Finally, lung cancer was at the first place in men, but at the second in females. CONCLUSIONS: All comorbidities increased their prevalence progressively up to the last stage of COPD severity, except the cardio-vascular and the metabolic ones which dropped in the IV GOLD stage, presumably due to the high mortality rate in this severe COPD stage. The gender-dependency of comorbidities was confirmed in general terms, even if lung cancer proved a dramatic increase almost independently of sex

Design, and participant enrollment, of a randomized controlled trial evaluating effectiveness and cost-effectiveness of a community-based case management intervention, for patients suffering from COPD

Sabrina Storgaard S&oslash;rensen,1 Kjeld M&oslash;ller Pedersen,1 Ulla M&oslash;ller Weinreich,2,3 Lars Holger Ehlers,1 1Danish Center for Healthcare Improvements, Faculty of Social Sciences and Faculty of Health Sciences, Aalborg University, Aalborg East, Denmark; 2Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 3The Clinical Institute, Aalborg University Hospital, Aalborg, Denmark Background: Case management interventions are recommended to improve quality of care and reduce costs in chronic care, but further evidence on effectiveness and cost-effectiveness is needed. The objective of this study is the reporting of the design and participant enrollment of a randomized controlled trial, conducted to evaluate the effectiveness and cost-effectiveness of a community-based case management model for patients suffering from chronic obstructive pulmonary disease (COPD). With a focus on support for self-care and care coordination, the intervention was hypothesized to result in a reduced number of COPD-related hospital admissions. Patients and methods: The design was a randomized controlled trial conducted from 2012 to 2014 with randomization and intervention at patient level. The study took place in Aalborg Municipality, a larger municipality in Denmark. A total of 150 COPD patients were randomized into two groups: the case-managed group and the usual-care group. Participant characteristics were obtained at baseline, and measures on effectiveness and costs were obtained through questionnaires and registries within a 12-month follow-up period. In the forthcoming analysis, effectiveness will be evaluated on COPD-related hospital admissions, mortality, health- related quality of life, and self-care. An economic evaluation will examine the cost-effectiveness of case management against current usual care from the perspective of the health care sector. Results: Baseline characteristics were comparable between the two groups except for the prevalence of cancer, which were borderline significantly higher in the case-managed group. This baseline difference will be adjusted for in the final analysis. A very low dropout rate for the intervention was observed, indicating that the intervention was well accepted. Conclusion: Presented in a forthcoming paper, the results of the study will provide new evidence to the future organization of case management. Keywords: personalized care, disease management, health-related quality of life, cost-effectiveness analysi

Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure

Line Hust Storgaard,1 Hans-Ulrich Hockey,2 Birgitte Schantz Laursen,3,4 Ulla M&oslash;ller Weinreich1,3 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Biometrics Matters Limited, Hamilton, New Zealand; 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Clinical Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark Background: This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT).Patients and methods: A total of 200 patients were randomized into usual care &plusmn; HFNC. At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1&nbsp;year before inclusion, modified Medical Research Council (mMRC) score, St George&rsquo;s Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO2) were recorded. Patients completed phone interviews at 1, 3 and 9&nbsp;months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12&nbsp;months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device.Results: The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p&lt;0.001). Modeled hospital admission rates were 0.79 versus 1.39/patient/year for 12- versus 1-month use of HFNC, respectively (p&lt;0.001). The HFNC group had improved mMRC scores from 3&nbsp;months onward (p&lt;0.001) and improved SGRQ at 6 and 12&nbsp;months (p=0.002, p=0.033) and PaCO2 (p=0.005) and 6MWT (p=0.005) at 12&nbsp;months. There was no difference in all-cause mortality.Conclusion: HFNC treatment reduced AECOPD, hospital admissions and symptoms in COPD patients with hypoxic failure. Keywords: COPD, high-flow heated and humidified oxygen, HFNC, exacerbation, AECOPD, modified Medical Research Council score, mMRC score, 6-minute walk test, 6MW

Association between hemoglobin and prognosis in patients admitted to hospital for COPD

Anne Pernille Toft-Petersen,1,2 Christian Torp-Pedersen,1,3 Ulla M&oslash;ller Weinreich,1,4 Bodil Steen Rasmussen1,2 1Department of Clinical Medicine, Aalborg University, 2Department of Anaesthesia and Intensive Care, 3Department of Clinical Epidemiology, 4Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark Abstract: Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD. There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known. A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established. Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved. Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin. The cohort encompassed 6,969 patients. Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females. The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively. After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22&ndash;1.73), adjusted HR 1.37 (95% CI 1.15&ndash;1.64). Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17&ndash;1.68), adjusted HR 1.28 (95% CI 1.06&ndash;1.53). In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality. Keywords: pulmonary disease, chronic obstructive, anemia, mortality, polycythemia, epidemiolog

Assisted ventilation in COPD &ndash; association between previous hospitalizations and mortality

Anne Pernille Toft-Petersen,1,2 Christian Torp-Pedersen,1,3 Ulla M&oslash;ller Weinreich,1,4 Bodil Steen Rasmussen1,2 1Department of Clinical Medicine, Aalborg University, 2Department of Anaesthesia and Intensive Care, Aalborg University Hospital, 3Department of Health, Science and Technology, Aalborg University, Aalborg, 4Department of Respiratory Medicine, Aalborg University Hospital,&nbsp;Denmark Background: In general, previous studies have shown an association between prior exacerbations and mortality in COPD, but this association has not been demonstrated in the subpopulation of patients in need of assisted ventilation. We examined whether previous hospitalizations were independently associated with mortality among patients with COPD ventilated for the first time. Patients and methods: In the Danish National Patient Registry, we established a cohort of patients with COPD ventilated for the first time from 2003 to 2011 and previously medicated for obstructive airway diseases. We assessed the number of hospitalizations for COPD in the preceding year, age, sex, comorbidity, mode of ventilation, survival to discharge, and days to death beyond discharge. Results: The cohort consisted of 6,656 patients of whom 66% had not been hospitalized for COPD in the previous year, 18% once, 8% twice, and 9% thrice or more. In-hospital mortality was 45%, and of the patients alive at discharge, 11% died within a month and 39% within a&nbsp;year. In multivariate models, adjusted for age, sex, mode of ventilation, and comorbidity, odds ratios for in-hospital death were 1.26 (95% confidence interval [CI]: 1.11&ndash;1.44), 1.43 (95% CI:&nbsp;1.19&ndash;1.72), and 1.56 (95% CI: 1.30&ndash;1.87) with one, two, and three or more hospitalizations, respectively. Hazard ratios for death after discharge from hospital were 1.32 (95% CI: 1.19&ndash;1.46), 1.76 (95% CI: 1.52&ndash;2.02), and 2.07 (95% CI: 1.80&ndash;2.38) with one, two, and three or more hospitalizations, respectively. Conclusion: Preceding hospitalizations for COPD are associated with in-hospital mortality and after discharge in the subpopulation of patients with COPD with acute exacerbation treated with assisted ventilation for the first time. Keywords: pulmonary disease, chronic obstructive, respiration, artificial, patient readmission, hospital mortality, critical car

The effect of comorbidities on COPD assessment: a pilot study

Ulla M&oslash;ller Weinreich,1&ndash;3 Lars Pilegaard Thomsen,2 Barbara Bielaska,4 Vania Helbo Jensen,5,6 Morten Vuust,4 Stephen Edward Rees2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Respiratory and Critical Care Group (RCARE), Centre for Model-Based Medical Decision Support Systems, Department of&nbsp;Health Science and Technology, Aalborg University, Aalborg, Denmark; 3The Clinical Institute, Aalborg University Hospital, Aalborg, Denmark; 4Department of Radiology, Vendsyssel Hospital, Hj&oslash;rring, Denmark; 5Department of Radiology, Horsens Regional Hospital, Horsens, Denmark; 6Department of Radiology, Aalborg University Hospital, Aalborg, Denmark Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from comorbidities. COPD severity may be evaluated by the Global initiative for chronic &shy;Obstructive Lung Disease (GOLD) combined risk assessment score (GOLD score). Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HR-CT) measure lung function and elucidate pulmonary pathology. This study assesses associations between GOLD score and measurements of lung function in COPD patients with and without (&le;1) comorbidities. It evaluates whether the presence of comorbidities influences evaluation by GOLD score of COPD severity, and questions whether GOLD score describes morbidity rather than COPD severity.Methods: In this prospective study, 106 patients with stable COPD were included. Patients treated for lung cancer were excluded. Demographics, oxygen saturation (SpO2), modified Medical Research Council Dyspnea Scale, COPD exacerbations, and comorbidities were recorded. Body plethysmography and DLCO were measured, and HR-CT performed and evaluated for emphysema and airways disease. COPD severity was stratified by the GOLD score. Correlation analyses: 1) GOLD score, 2) emphysema grade, and 3) airways disease and lung function parameters, described by: forced expiratory volume in the first second in percent of expected value (FEV1%), inspiratory capacity (IC%), total lung volume (TLC%), IC/TLC, and SpO2. Correlation analyses between subgroups and hierarchical cluster analysis were performed.Results: Significant associations were found between GOLD score and both emphysema grade (correlation coefficients [cc]: -0.2, P=0.03) and lung function parameters (cc: -0.5 to -0.7, P-values all &lt;0.001) weakened in patients with &gt;1 comorbidity (cc: -0.4 to -0.5, P-values all 0.001). Significant differences between subgroups were found in GOLD score and both FEV1% (cc: -0.2, P=0.02) and IC/TLC (cc: -0.2, P=0.02). Comorbidities were associated with GOLD score and composite measures in hierarchical cluster analysis. Conclusion: The presence of comorbidities influences the relationship between GOLD score and lung function measurements. GOLD score may be more representative of morbidity than of COPD severity. Keywords: GOLD, diffusing capacity of the lung for carbon monoxide, high resolution computerized tomography, mMRC, total lung capacity, inspiratory capacit