Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial

OBJECTIVE To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN Prospective observational study. SUBJECTS AND METHODS Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis. CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes : A Historical Matched Cohort Study

Funding: The analyses were funded by Boehringer Ingelheim. Access to data from the Optimum Patient Care Research Database was co-funded by Research in Real Life Ltd. The funder, Boehringer Ingelheim, had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Rafael Mares is employed by Research in Real Life Ltd., which provided support in the form of salary for author RM but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.

Eligibility of real-life patients with COPD for inclusion in trials of inhaled long-acting bronchodilator therapy

Data access and analyses were funded by Boehringer Ingelheim, who played no role in the conduct or reporting of the study.

Effects of proportional assisted ventilation on exercise performance in idiopathic pulmonary fibrosis patients

Background: Patients with idiopathic pulmonary fibrosis (IPF) present an important ventilatory (imitation reducing their exercise capacity. Non-invasive ventilatory support has been shown to improve exercise capacity in patients with obstructive diseases; however, its effect on IPF patients remains unknown. Objective: The present study assessed the effect of ventilatory support using proportional, assist ventilation (PAV) on exercise capacity in patients with IPF. Methods: Ten patients (61.2 +/- 9.2 year-old) were submitted to a cardiopulmonary exercise testing, plethysmography and three submaximal. exercise tests (60% of maximum load): without ventilatory support, with continuous positive airway pressure (CPAP) and PAV. Submaximal tests were performed randomly and exercise capacity, cardiovascular and ventilatory response as well as breathlessness subjective perception were evaluated. Lactate plasmatic levels were obtained before and after submaximal. exercise. Results: Our data show that patients presented a limited exercise capacity (9.7 +/- 3.8 mL O(2)/kg/min). Submaximal. test was increased in patients with PAV compared with CPAP and without ventilatory support (respectively, 11.1 +/- 8.8 min, 5.6 +/- 4.7 and 4.5 +/- 3.8 min; p < 0.05). An improved arterial oxygenation and lower subjective perception to effort was also observed in patients with IPF when exercise was performed with PAV (p < 0.05). IPF patients performing submaximal exercise with PAV also presented a lower heart rate during exercise, although systolic and diastolic pressures were not different among submaximal tests. Our results suggest that PAV can increase exercise tolerance and decrease dyspnoea and cardiac effort in patients with idiopathic pulmonary fibrosis. (C) 2009 Elsevier Ltd. All rights reserved.

Is multidimensional scaling suitable for mapping the input respiratory impedance in subjects and patients?

This paper presents the application of multidimensional scaling (MDS) analysis to data emerging from noninvasive lung function tests, namely the input respiratory impedance. The aim is to obtain a geometrical mapping of the diseases in a 3D space representation, allowing analysis of (dis)similarities between subjects within the same pathology groups, as well as between the various groups. The adult patient groups investigated were healthy, diagnosed chronic obstructive pulmonary disease (COPD) and diagnosed kyphoscoliosis, respectively. The children patient groups were healthy, asthma and cystic fibrosis. The results suggest that MDS can be successfully employed for mapping purposes of restrictive (kyphoscoliosis) and obstructive (COPD) pathologies. Hence, MDS tools can be further examined to define clear limits between pools of patients for clinical classification, and used as a training aid for medical traineeship.

New auxiliary indicators for the differential diagnosis of functional cardiorespiratory limitation in patients with chronic obstructive pulmonary disease and congestive heart failure

OBJECTIVE: To differentiate the nature of functional cardiorespiratory limitations during exercise in individuals with chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) and to determine indicators that may help their classifications. METHODS: The study comprised 40 patients: 23 with COPD and 17 with CHF. All individuals underwent maximal cardiopulmonary exercise testing on a treadmill. RESULTS: The values of peak gas exchange ratio (R peak), peak carbon dioxide production (VCO2 peak), and peak oxygen ventilatory equivalent (V E O2 peak) were higher in the patients with CHF than in those with COPD, and, therefore, those were the variables that characterized the differences between the groups. For group classification, the differentiating functions with the R peak, VCO2 peak (L/min), and V E O2 peak variables were used as follows: group COPD: - 44.886 + 78.832 x R peak + 5.442 x VCO2 peak + 0.336 x V E O2 peak; group CHF: - 69.251 + 89.740 x R peak + 8.461 x VCO2 peak + 0.574 x V E O2 peak. The differentiating function, whose result is greater, correctly classifies the patient's group as 90%. CONCLUSION: The R peak, VCO2 peak, and V E O2 peak values may be used to identify the cause of the functional cardiorespiratory limitations in patients with COPD and CHF.

Nouvelles pistes pour la réhabilitation respiratoire dons la bronchopneumopathie chronique obstructive (BPCO) [New perspectives for respiratory rehabilitation in COPD].

COPD is associated with some skeletal muscle dysfunction which contributes to a poor exercise tolerance. This dysfunction results from multiple factors: physical inactivity, corticosteroids, smoking, malnutrition, anabolic deficiency, systemic inflammation, hypoxia, oxidative stress. Respiratory rehabilitation is based on exercise training and allows patients with COPD to experience less dyspnoea, and to improve their exercise tolerance and quality of life. Not all patients, however, benefit from rehabilitation. Acknowledging the different factors leading to muscular dysfunction allows one to foresee new avenues to improve efficacy of exercise training in COPD.

Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD. METHODS: Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order. RESULTS: FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4). CONCLUSION: Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.

Clinical characteristics and outcome of patients admitted to a medico- surgical ICU requiring non invasive ventilation (NIV) for hypercapnic respiratory failure

Introduction Because it decreases intubation rate and mortality, NIV has become first-line treatment in case of hypercapnic acute respiratory failure (HARF). Whether this approach is equally successful for all categories of HARF patients is however debated. We assessed if any clinical characteristics of HARF patients were associated with NIV intensity, success, and outcome, in order to identify prognostic factors. Methods Retrospective analysis of the clinical database (clinical information system and MDSi) of patients consecutively admitted to our medico-surgical ICU, presenting with HARF (defined as PaCO2 > 50 mmHg), and receiving NIV between May 2008 and December 2010. Demographic data, medical diagnoses (including documented chronic lung disease), reason for ICU hospitalization, recent surgical interventions, SAPS II and McCabe scores were extracted from the database. Total duration of NIV and the need for tracheal intubation during the 5 days following the first hypercapnia documentation, as well as ICU, hospital and one year mortality were recorded. Results are reported as median [IQR]. Comparisons were carried out with Chi2 or Kruskal-Wallis tests, p<0.05 (*). Results Two hundred and twenty patients were included. NIV successful patients received 16 [9-31] hours of NIV for up to 5 days. Fifty patients (22.7%) were intubated 11 [2-34] hours after HARF occurence, after having receiving 10 [5-21] hours of NIV. Intubation was correlated with increased ICU (18% vs. 6%, p<0.05) and hospital (42% vs. 31%, p>0.05) mortality. SAPS II score was related to increasing ICU (51 [29-74] vs. 23 [12-41]%, p<0.05), hospital (37% [20-59] vs 20% [12-37], p<0.05) and one year mortality (35% vs 20%, p<0.05). Surgical patients were less frequent among hospital fatalities (28.8% vs. 46.3%, p<0.05, RR 0.8 [0-6-0.9]). Nineteen patients (8.6%) died in the ICU, 73 (33.2%) during their hospital stay and 108 (49.1%) were dead one year after HARF. Conclusion The practice to start NIV in all suitable patients suffering from HARF is appropriate. NIV can safely and appropriately be used in patients suffering from HARF from an origin different from COPD exacerbation. Beside usual predictors of severity such as severity score (SAPS II) appear to be associated with increased mortality. Although ICU mortality was low in our patients, hospital and one year mortality were substantial. Surgical patients, although undergoing a similar ICU course, had a better hospital and one year outcome.

Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010.

The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.

Pulmonary biomarkers in COPD exacerbations: a systematic review.

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease's clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.

Prise en charge du patient avec bronchopneumopathie obstructive: ambulatoire ou hospitalière [Management of the patient with COPD: home case or hospitalization].

Acute exacerbation of COPD is one of the most common causes of hospital admission in patients affected with this disease. In most cases, consideration of differential diagnoses and assessment of important comorbidities will allow to make the decision whether or not the patient needs to be hospitalized. A decision to hospitalize will be based on specific symptoms and signs, as well on the patient's history. Contrary to bronchial asthma, a systematic action plan strategy is lacking for COPD. However, a disease management plan involving all the health care providers may have the potential to improve the patient's well being and to decrease costs related to these exacerbations.

Head-to-head comparison of length of stay, patients' outcome and satisfaction in Switzerland before and after SwissDRG-Implementation in 2012 in 2012: an observational study in two tertiary university centers.

On 1 January 2012 Swiss Diagnosis Related Groups (DRG), a new uniform payment system for in-patients was introduced in Switzerland with the intention to replace a "cost-based" with a "case-based" reimbursement system to increase efficiency. With the introduction of the new payment system we aim to answer questions raised regarding length of stay as well as patients' outcome and satisfaction. This is a prospective, two-centre observational cohort study with data from University Hospital Basel and the Cantonal Hospital Aarau, Switzerland, from January to June 2011 and 2012, respectively. Consecutive in-patients with the main diagnosis of either community-acquired pneumonia, exacerbation of COPD, acute heart failure or hip fracture were included. A questionnaire survey was sent out after discharge investigating changes before and after SwissDRG implementation. Our primary endpoint was LOS. Of 1,983 eligible patients 841 returned the questionnaire and were included into the analysis (429 in 2011, 412 in 2012). The median age was 76.7 years (50.8% male). Patients in the two years were well balanced in regard to main diagnoses and co-morbidities. Mean LOS in the overall patient population was 10.0 days and comparable between the 2011 cohort and the 2012 cohort (9.7 vs 10.3; p = 0.43). Overall satisfaction with care changed only slightly after introduction of SwissDRG and remained high (89.0% vs 87.8%; p = 0.429). Investigating the influence of the implementation of SwissDRG in 2012 regarding LOS patients' outcome and satisfaction, we found no significant changes. However, we observed some noteworthy trends, which should be monitored closely.