Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Reduced sputum expression of interferon-stimulated genes in severe COPD

BACKGROUND: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients. METHODS: Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-beta) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology. RESULTS: Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-beta was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%). ISGs were easily detectable in both groups. In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects. No difference was found with respect to MxA. COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients. Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts. IFN-beta expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs. CONCLUSION: ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection

Pulmonary rehabilitation and COPD: providing patients a good environment for optimizing therapy

Jean-Louis Corhay, Delphine Nguyen Dang, H&eacute;l&egrave;ne Van Cauwenberge, Renaud Louis Department of Pneumology, Centre Hospitalier Universitaire du Sart-Tilman Li&egrave;ge, Li&egrave;ge, Belgium Abstract: Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient&#39;s disability and poor health-related quality of life (HRQoL). Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea&ndash;decreased activity&ndash;deconditioning&ndash;isolation. Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity. Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines. This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. Keywords: chronic obstructive pulmonary disease, exercise training, physical activity, quality of lif

Inhaled treatment of COPD: a Delphi consensus statement

Vincent Ninane,1 Jean-Louis Corhay,2 Paul Germonpr&eacute;,3 Wim Janssens,4 Guy F Joos,5 Giuseppe Liistro,6 Walter Vincken,7 Sandra Gurdain,8 Evelyne Vanvlasselaer,8 An Lehouck8 1Department of Respiratory Medicine, Saint-Pierre Hospital, Universit&eacute; Libre de Bruxelles, Brussels, 2Department of Respiratory Medicine, CHU, Liege, 3Department of Respiratory Medicine, AZ Maria Middelares, Ghent, 4Department of Respiratory Medicine, Katholieke Universiteit, Leuven, 5Department of Respiratory Medicine, Ghent University Hospital, Ghent, 6Department of Respiratory Medicine, University Hospitals Saint-Luc, Brussels, 7Department of Respiratory Medicine, University Hospital Brussels, Brussels, 8Medical Department, Novartis Pharma, Vilvoorde, Belgium Background: Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first-choice options per GOLD category without specification. Objectives: To evaluate the level of medical experts&rsquo; consensus on their preferred first-choice treatment within different COPD categories. Methods: A two-round Delphi Panel consisting of 15 questions was completed by Belgian pulmonologists (n=31) and European (n=10) COPD experts. Results: Good consensus was reached by both expert groups for long-acting bronchodilators instead of short-acting bronchodilators as first-choice treatment in GOLD A. Single bronchodilation with long-acting muscarinic antagonist (LAMA) was preferred over long-acting &szlig;2-agonist (LABA) and LABA/LAMA as first-choice treatment in GOLD B and GOLD C. For GOLD D patients based on the forced expiratory volume in 1 second (FEV1)&lt;50%, a very good consensus was reached for LAMA/LABA as first-choice treatment. For GOLD D patients based on frequent or severe exacerbations, there was a good consensus for LABA/LAMA/inhaled corticosteroids (ICS) as first choice in the Belgian group. According to the European experts, both LABA/LAMA and LABA/LAMA/ICS could be the first choice for these patients. Conclusion: Belgian and European experts recommend long-acting bronchodilators as first-choice treatment. Treatment containing ICS was found only appropriate in patients with FEV1&lt;50% and &ge;2 moderate exacerbations or 1 severe exacerbation/year. Keywords: chronic obstructive pulmonary disease, therapy, long acting muscarinic antagonist, long acting beta agonist, inhaled corticosteroids, guideline

Reduced sputum expression of interferon-stimulated genes in severe COPD

Clarissa Hilzendeger,1 Jane da Silva,2 Monique Henket,1 Florence Schleich,1 Jean Louis Corhay,1 Tatiana Kebadze,3 Michael R Edwards,3 Patrick Mallia,3 Sebastian L Johnston,3 Renaud Louis1 1Department of Respiratory Medicine, Centre Hospitalier Universitaire (CHU) Liege, Groupe Interdisciplinaire de G&eacute;noprot&eacute;omique Appliqu&eacute;e (GIGA) I3 University of Liege, Belgium; 2Department of Medicine, Post-graduate Program in Health Sciences, University of Southern Santa Catarina, Palho&ccedil;a-SC, Brazil; 3Airway Disease Division, Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, London, UK Background: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients.Methods: Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-&beta;) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.Results: Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-&beta; was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%). ISGs were easily detectable in both groups. In the whole group of COPD patients, OAS expression was decreased (P&lt;0.05), while that of viperin was increased (P&lt;0.01) compared to healthy subjects. No difference was found with respect to MxA. COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P&lt;0.01 for MxA, P&lt;0.05 for OAS, and P&lt;0.01 for viperin) as compared to those of group B patients. Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts. IFN-&beta; expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.Conclusion: ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. Keywords: COPD, innate immunity, interferon-&beta;, interferon-&lambda;1, interferon-stimulated gene

A Belgian survey on the diagnosis of asthma&ndash;COPD overlap syndrome

Didier Cataldo,1 Jean-Louis Corhay,1 Eric Derom,2 Renaud Louis,1 Eric Marchand,3,4 Alain Michils,5 Vincent Ninane,6 Rudi Pech&eacute;,7 Charles Pilette,8 Walter Vincken,9 Wim Janssens10 1Department of Respiratory Diseases, CHU Li&egrave;ge, University of Li&egrave;ge, Li&egrave;ge, 2Department of Respiratory Medicine, Ghent University Hospital, Ghent, 3Department of Respiratory Medicine, CHU &ndash; UCL &ndash; Namur, Universit&eacute; catholique de Louvain, Yvoir, 4Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, 5Chest Department, Erasme University Hospital, Universit&eacute; Libre de Bruxelles, Brussels, 6Department of Respiratory Medicine, University Hospital Saint-Pierre, Universit&eacute; Libre de Bruxelles, Brussels, 7Department of Respiratory Medicine, University Hospital V&eacute;sale, Montigny-le-Tilleul, 8Department of Respiratory Medicine, Cliniques universitaires St Luc, Universit&eacute; Catholique de Louvain, Brussels, 9Respiratory Division, University Hospital Brussels (UZ Brussel), Vrije Universiteit Brussel, Brussels, 10Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium Introduction: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma&ndash;COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS.Methods: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by &ge;70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient.Results: To diagnose ACOS in COPD patients, major criteria were &ldquo;high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second &ge;400 mL)&rdquo; and &ldquo;high degree of response to bronchodilators (&gt;200 mL and &ge;12% predicted above baseline)&rdquo;. Minor criteria were &ldquo;personal/family history of atopy and/or IgE sensitivity to &ge;1 airborne allergen&rdquo;, &ldquo;elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide&rdquo;, &ldquo;diagnosis of asthma &lt;40 years of age&rdquo;; &ldquo;symptom variability&rdquo;, and &ldquo;age (in favor of asthma)&rdquo;. To diagnose ACOS in asthma patients, major criteria were &ldquo;persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio &lt;0.7)&rdquo; and &ldquo;exposure to noxious particles/gases, with &ge;10 pack-years for (ex-)smokers&rdquo;; minor criteria were &ldquo;lack of response on acute bronchodilator test&rdquo;; &ldquo;reduced diffusion capacity&rdquo;; &ldquo;limited variability in airway obstruction&rdquo;; &ldquo;age &gt;40 years&rdquo;; &ldquo;emphysema on chest computed tomography scan&rdquo;.Conclusion: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. Keywords: ACOS, airway obstruction, asthma, COPD, diagnosis, inhaled corticosteroids&nbsp